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ABSTRACT: In studying a site-targeted contrast agent that can be administered as nano-particle (liquid droplet) and change its phase from liquid to gas by an external stimulus such as ultrasound to yield microbubbles, we have investigated if the phase shift can be achieved by using short pulses produced by a medical ultrasound scanner and probe. As expected in a preliminary study, we could induce phase shift by using pulsed ultrasound with several MPa negative peak pressure in in vitro experiments by using a linear probe with the frequency range of 3-8 MHz. It was found that the higher the ultrasound frequency, the lower the threshold, which indicated a thermal mechanism in phase shift. However, exposed total energy did not seem to be important to induce the phase shift because increasing wave cycle numbers from 2 to 8 did not lower the threshold significantly. Also it was suggested that negative peak pressure amplitude seemed to play a major role and positive peak did not. In vivo experiments with mice tumor exhibited that microbubble can also be generated in living bodies with ultrasound pulses generated by the ultrasound scanner at the same negative peak pressure amplitude as in in vitro experiments at the frequency of 7.8 MHz
Ultrasonics Symposium, 2006. IEEE; 11/2006
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ABSTRACT: The pharmacokinetics and tissue distribution of photofrin II (PF) and its efficacy in sonodynamic therapy were studied in rats bearing AH130 solid tumors.
In order to find the optimum timing of the ultrasound exposure after administration of PF, the PF concentrations in plasma, skin, muscle and tumor were measured and pharmacokinetically analyzed. Antitumor effects were estimated by measuring tumor size.
Since the highest concentration of PF in tumors occurred 24 h after administration, ultrasound administration 24 h after the intravenous administration of PF was chosen. Ultrasound alone showed a slight antitumor effect, which became increasingly significant as the dose of PF was increased, while PF alone showed no significant effect.
PF significantly sensitized solid tumors to the antitumor effect of ultrasound in a synergistic manner.
Cancer Chemotherapy and Pharmacology 03/2003; 51(2):174-8. · 2.83 Impact Factor
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ABSTRACT: Surgical reconstruction of bony defects such as Rotational Acetabular Osteotomy (RAO) in the orthopedics field involves the operation of bony cutting using surgical saws or drills. Operators have to incise skin and open the muscular system under anesthesia to make the bone visible, and this causes patients great pain and marks after the operation. So a system of bony cutting using focused ultrasound without incising the skin has been developed. The ultrasound energy and the high pressure caused by cavitation generated by the minus vapor pressure ablates the focus area of the bone. An experiment of ablating the surface of a pig's bone by ultrasound was carried out in various irradiation conditions. At a high oscillating frequency, in the case of continuum waves, the mark of ablation without thermal damage was found at the focal point and the size was the same as the convergence beam area of the ultrasonic wave. In addition, ultrasonic propagation in the living body which consists of multiple organizations was analyzed using the time-domain finite element method. In comparison with the experimental result, some important parameters relating to the cause of thermal damage at the focus on the bone were specified.
Engineering in Medicine and Biology, 2002. 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society EMBS/BMES Conference, 2002. Proceedings of the Second Joint; 11/2002
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ABSTRACT: Coded excitation requires long code to improve signal to noise ratio (SNR). However, in order to achieve a high lateral resolution, the beam forming is normally performed based on a low f-number and real-time dynamic focusing, which limits the maximum length of coded waves. Individual decoding before beamforming can solve this problem, but it demands an enormous size of hardware. In this study, a subaperture decoding technique is proposed to achieve a high SNR based on coded excitation without compromising lateral resolution. In this technique, the receiving aperture is divided into N subapertures, beamforming is performed for each subaperture, and each output is decoded, delayed and summed together to complete beamforming in whole aperture. Computer simulations were used to demonstrate this technique. When the transmission waveform was encoded by the 13-chip Barker code and decoded with a mismatched filter, and the reception f-number was 1, the proposed technique, with the number of subaperture of 16, lowered the range sidelobe level from -25 dB to -45 dB.
Ultrasonics Symposium, 2002. Proceedings. 2002 IEEE; 11/2002
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ABSTRACT: The sonodynamically induced antitumor effect of Photofrin II (PF), was evaluated in mice bearing colon 26 carcinoma. In order to find the optimum timing for ultrasonic exposure after the administration of PF, the PF concentrations in the plasma, skin, muscle, and tumor were measured. The antitumor effect was estimated by measuring the tumor size. Since the highest concentration of PF in the tumor was observed 24 h after administration, an ultrasonic exposure timing of 24 h after the intravenous administration of PF was chosen. When used alone, ultrasound showed a slight antitumor effect, which became increasingly significant as the dose of PF was increased, while use of PF alone showed no significant effect. From these results, it is concluded that PF significantly sensitizes solid tumors to ultrasound, demonstrating a synergistic antitumor effect.
Journal of Cancer Research and Clinical Oncology 11/2000; 126(10):601-6. · 2.56 Impact Factor
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Z H Jin,
N Miyoshi,
K Ishiguro, S Umemura,
K Kawabata,
N Yumita,
I Sakata,
K Takaoka,
T Udagawa,
S Nakajima,
H Tajiri,
K Ueda,
M Fukuda,
M Kumakiri
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ABSTRACT: We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.
The Journal of Dermatology 05/2000; 27(5):294-306. · 1.49 Impact Factor
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ABSTRACT: The sonodynamically induced antitumor effect of 4-formyloximethylidene-3-hydroxy-2-vinyl-deuterio-porphyn yl(IX)-6,7-diaspartic acid (ATX-S10) was investigated. Both in vitro and in vivo antitumor effects were tested in combination with ultrasound at 2 MHz. The rate of ultrasonically induced damage to isolated sarcoma 180 cells in air-saturated suspension was enhanced two-fold with 80 microM ATX-S10. This enhancement was significantly inhibited by histidine, which may suggest that it was mediated by ultrasonically induced oxidation. The coadministraion of 25 mg/kg ATX-S10 followed by ultrasonic exposure at 2 MHz stopped the growth of implanted colon 26 tumors at an intensity at which ultrasound alone showed only a slight antitumor effect.
Japanese journal of cancer research: Gann 03/2000; 91(2):255-60.
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ABSTRACT: The ultrasonically induced effect of rose bengal (RB) on isolated tumor cells was investigated.
Sarcoma 180 cells were suspended in air-saturated phosphate-buffered saline and exposed to ultrasound in standing wave mode for up to 60 s in the presence and absence of RB. Cell viability was determined by the ability to exclude trypan blue.
The rate of inducing cell damage by ultrasound was enhanced two to three times with 160 microM RB. while no cell damage was observed with RB alone. This enhancement was significantly inhibited by histidine.
Ultrasonically induced in vitro cell damage was significantly enhanced by RB. A sonochemical mechanism may be suggested since the enhancement was significantly inhibited by an active oxygen scavenger.
Cancer Chemotherapy and Pharmacology 02/1999; 43(5):389-93. · 2.83 Impact Factor
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ABSTRACT: The antitumor effect of focused ultrasound in combination with Ga-porphyrin complex, 7,12-bis(1-decyloxyethyl)-Ga(III)-3,8,13,17 tetramethylporphyrin-2,18-dipropionyl diaspartic acid (ATX-70), on the growth of experimental murine tumors was examined. Walker 256 tumors implanted in rat kidneys were exposed in a progressive wave field for 5 min to focused ultrasound at 500 kHz with the second harmonic (at 1 MHz) superimposed after administration of ATX-70 to the rats. A significant antitumor effect was obtained at a focal-spot average acoustic intensity of 12 W/cm2 or higher with an ATX-70 dose of not less than 2.5 mg/kg. When the acoustic intensity was 8 W/cm2 or lower, no significant effect was observed even at an ATX-70 dose of 2.5 mg/kg. Also when the ATX-70 dose was 1.0 mg/kg or lower, no significant effect was observed even at a focal-spot average acoustic intensity of 40 W/cm2.
Japanese journal of cancer research: Gann 05/1998; 89(4):452-6.
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ABSTRACT: The ultrasonically-induced in vitro cell damaging effect of fluorine-containing anthracycline derivative (FAD104) was investigated. Sarcoma 180 cells suspended in air-saturated PBS were exposed to ultrasound for up to 60 s in the presence and absence of FAD104. The rate of inducing cell damage with ultrasound was doubled with 80 microM FAD104, while no cell damage was observed with FAD104 alone. This enhancement was significantly inhibited by histidine, which may suggest a sonochemical mechanism.
Cancer Letters 04/1998; 125(1-2):209-14. · 4.24 Impact Factor
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ABSTRACT: Sonodynamically-induced cell damage and active oxygen generation enhanced by adriamycin (ADM) were compared in the same in vitro insonation set-up. Significant enhancement of the rates of both ultrasonically-induced cell damage and nitroxide generation was demonstrated with 40-160 microM ADM. Both rates correlated very well resulting in a correlation coefficient of more than 0.99. The enhancement of both rates was suppressed by 10 mM histidine. These results are consistent with the hypothesis that ultrasonically-generated active oxygen plays a major role in the sonodynamically-induced cell damage enhanced by ADM.
Cancer Letters 01/1998; 121(2):195-201. · 4.24 Impact Factor
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ABSTRACT: The antitumor effect of a gallium-porphyrin complex, ATX-70, induced by focused ultrasound, on colon 26 carcinoma implanted in a mouse kidney was investigated. Colon 26 tumors were exposed to focused ultrasound at 500 kHz and 1 MHz in a progressive wave mode. Both frequency components were superimposed onto each other in the focal zone to efficiently produce cavitation in the tumor. ATX-70 was administered intravenously at the dose of 2.5 mg/kg, 24 h before the ultrasonic exposure. Antitumor effects were evaluated by histological observation 7 days after the exposure. The destruction of tumor tissue was observed with the ultrasonic treatment in combination with ATX-70, while neither the treatment with ATX-70 alone nor that with ultrasound alone caused any necrosis. These results first demonstrated that antitumor effects of a porphyrin compound can be induced by focused ultrasound in a progressive wave mode.
Cancer Letters 02/1997; 112(1):79-86. · 4.24 Impact Factor
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ABSTRACT: The sonodynamically induced antitumor effect of pheophorbide a (Ph-a) was investigated. Both in vitro and in vivo effects on sarcoma 180 were tested in combination with ultrasound at 2 MHz. The rate of ultrasonically induced cell damage in air-saturated suspension was enhanced by twice with 80 microM Ph-a. This enhancement was significantly inhibited by histidine, which may suggest it was mediated by ultrasonically induced oxidation. For mice, 5 mg/kg Ph-a was administered before the insonation, and ultrasound stopped the tumor growth at an intensity with which ultrasound alone showed only a slight antitumor effect.
Cancer Letters 05/1996; 102(1-2):151-7. · 4.24 Impact Factor
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ABSTRACT: The sonodynamically induced antitumor effect of a gallium-porphyrin complex, ATX-70, was evaluated in mice bearing colon 26. In order to find the optimum timing for the ultrasonic exposure after the administration of ATX-70, the ATX-70 concentrations in the plasma, skin, and tumor were measured and analyzed. Antitumor effect was estimated by measuring the tumor size. When used alone, ultrasound showed a slight antitumor effect, which became increasingly significant as the dose of ATX-70 was increased, while use of ATX-70 alone had no significant effect. At an ATX-70 dose of 2.5 mg/kg or higher, the average tumor size decreased to smaller than a half by three days after the ultrasonic exposure. This was smaller than a third of the size of the untreated tumors on the same day. From these results, it is concluded that ATX-70 significantly sensitizes tumors to ultrasound, demonstrating a synergistic antitumor effect.
Japanese journal of cancer research: Gann 04/1996; 87(3):310-6.
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ABSTRACT: Sonodynamically induced lipid peroxidation with haematoporphyrin (Hp) was studied using rat erythrocytes. Both suspensions of erythrocyte ghosts and of intact erythrocytes were exposed to ultrasound in the same way in the presence and absence of Hp (80 microM). The lipid peroxidation in erythrocyte ghost membranes was estimated by measuring the amount of reactive substance produced from thiobarbituric acid added immediately after the exposure. Haematoporphyrin multiplied the ultrasonically induced lipid peroxidation by three to five times, while Hp alone showed no peroxidation. A 24-h interval between the exposure and the preparation for measurement did not increase the measured amount of peroxide. In the presence of Hp the estimated peroxidation rate and the rate of erythrocyte lysis correlated quite well for each acoustic condition and for each chemical condition such as the presence or absence of active oxygen scavengers in the suspension. The sonodynamically induced lipid peroxidation with Hp was doubled by deuterium oxide substitution for suspension medium and was significantly reduced by histidine, by sodium azide, and also by nitrogen substitution for saturation gas, whereas superoxide dismutase and mannitol showed no significant inhibitory effect. These results are consistent with a hypothesis that lipid peroxidation in membranes by singlet oxygen is the primary mechanism of sonodynamically induced erythrocyte lysis with Hp.
International Journal of Radiation Biology 04/1996; 69(3):397-404. · 2.28 Impact Factor
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ABSTRACT: The production of 2,2,6,6-tetramethyl-4-piperidone-N-oxyl by reaction of 2,2,6,6-tetramethyl-4-piperidone (TMPone) with ultrasonically generated active species in oxygenated solutions of hematoporphyrin (Hp) was studied by electron spin resonance spectroscopy. The nitroxide production rate in air-saturated TMPone solutions in phosphate-buffered saline of pH 9.0 was significantly higher in the presence of Hp than in its absence. The enhancement of nitroxide production by Hp was significantly inhibited in the presence of sodium azide or histidine in the solution. The production rate with Hp was doubled by substitution of deuterium oxide, while the rate without Hp increased only modestly. These results suggest that a substantial amount of active oxygen can be generated by ultrasound in aqueous solutions of Hp. Since the production rate was not reduced by mannitol and no nitroxide was produced in nitrogen-saturated solutions, it appears that hydroxyl radicals do not account for a major portion of the active oxygen species which reacted with TMPone to yield a nitroxide.
Radiation Research 06/1994; 138(2):171-6. · 2.68 Impact Factor
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ABSTRACT: Effect of second-harmonic superimposition on cavitation and
sonochemical reaction was investigated in a propagation mode by using a
plane wave transducer piezoelectrically active at both fundamental and
second-harmonic frequencies. The rate of iodine release induced by
ultrasound at 1 MHz with a superimposed wave at 2 MHz showed significant
dependence on the phase relation between the two waves. The largest rate
was obtained at the relative phase which maximizes the magnitude of
negative peak pressure while almost no iodine release was observed at
the relative phase which maximizes the magnitude of positive peak
pressure. At this optimum relative phase, the dependence of iodine
release and subharmonic emission on the ultrasound power at 1 MHz and 2
MHz was studied. The results clearly show the synergistic effects of the
fundamental and second harmonic on the chemical reaction and on
higher-order subharmonic emission which typically accompanies acoustic
cavitation
Ultrasonics Symposium, 1993. Proceedings., IEEE 1993; 12/1993
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ABSTRACT: Enhancement of ultrasonically induced cell damage by a gallium-porphyrin complex [ATX-70, 2,4-bis(1-decyloxyethyl)-Ga(III)-1,3,5,8- tetramethylporphryin-6,7-dipropionyl diaspartic acid] was investigated. The rate of damage to isolated sarcoma 180 cells in air-saturated suspension induced by 2 MHz ultrasound irradiation was enhanced more than four times by 80 microM ATX-70 in contrast to only twice by the same concentration of hematoporphyrin (Hp). The enhancement was almost completely inhibited in the presence of 10 mM histidine in the suspension, but not at all by 100 mM mannitol, which suggests that the enhanced cell damage was mostly mediated by singlet oxygen. Ultrasonically induced active oxygen generation in an air-saturated aqueous solution of ATX-70 was studied by detecting the electron spin resonance signals of 2,2,6,6,-tetramethyl-4-piperidone-N-oxyl produced by the reaction of 2,2,6,6-tetramethyl-4-piperidone with the generated active oxygen species. The rate of ultrasonically induced nitroxide generation was enhanced five times by 80 microM ATX-70 in contrast to only twice by Hp. The enhancement was inhibited significantly in the presence of 10 mM histidine in the suspension, but not at all by 100 mM mannitol. The singlet oxygen generation in air-saturated aqueous solution was further confirmed by the bleaching of N,N-dimethyl-4-nitrosoaniline in the presence of imidazole. The ultrasonically induced bleaching rate was enhanced six times by ATX-70, in contrast to only twice by Hp.
Japanese journal of cancer research: Gann 06/1993; 84(5):582-8.
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ABSTRACT: Chemical agents such as hematoporphyrin have been found to have a sonochemical activity to induce anti-tumor effects. The same kind of sonochemical reactions producing active oxygen species has been demonstrated to be localized with a highly focused ultrasound in a specially developed tissue-mimicking phantom. These results suggest that the focused ultrasound irradiation to a tumor combined with administration of such a sonochemically active agent can be a potential low-invasive modality for cancer therapy.
Engineering in Medicine and Biology Society, 1992 14th Annual International Conference of the IEEE; 12/1992
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ABSTRACT: 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
Ultrasonics Symposium, 1992. Proceedings., IEEE 1992; 11/1992
