We measured the localized transient temperature of Ho:YAG laser induced bubble in water by infrared radiation measurement with a infrared optical fiber to study heat effect/damage of this bubble for vascular therapeutic applications. Although there have been many reports regarding to the temperature in the Ho:YAG laser induced bubble by both theoretical and experimental approaches, we can not find well-time-response reliable temperature in the laser induced bubble. We constructed the remote temperature measurement system to obtain the temperature of the laser induced bubble with the infrared optical fiber (Optran MIR, CeramOptec) made of AgCl/AgBr with 1mm in core diameter. The flash lamp excited Ho: YAG laser (IH102, NIIC,λ=2.1μm) beam was delivered through a silica optical fiber (core diameter: 600μm) and was irradiated from the fiber tip in water. The tip position of the infrared optical fiber against the silica glass fiber was changed to measure local bubble temperature. The sidewall of the infrared optical fiber tip was covered by a black rubber tube to prevent the collection of the Ho:YAG laser into the infrared fiber. The infrared radiation delivered through the infrared optical fiber was measured by the HgCdTe infrared detector (KMPC12-2-J1, Kolmar Technologies, rise time:500ns). This fiber optic radiation detection system was calibrated before the bubble temperature measurement. Since the bubble boundary location and its shape were changed with time, we corrected influences of these factors. We finally obtained the peak temperature of 61.7±2.8°C at the top surface in the laser induced bubble with 800mJ/pulse. This temperature was 10 degree lower than that of reported. The temperature at the top of the bubble was approximately 9.8 degree higher than that at the bubble side. Obtained temperature distribution with time may be available to study bubble dynamics necessary for our vascular applications.
In order to investigate the optimum operation parameters on novel short-term heating (<15s, approx. 70oC) balloon,
named Photo-thermo dynamic balloon (PTDB), we studied diameter and elasticity change of vascular wall after
dilatation ex vivo. We have been studying to develop the PTDB angioplasty in which we demonstrated sufficient
vascular dilatation with lower pressure by heat- induced denaturation of arterial collagen. And we have also
demonstrated the suppression of intimal hyperplasia in animal experiments. We need to understand the PTDB dilatation
mechanism to determine the optimum operation parameters. The prototype PTDB with diameter of 3mm was used in
our experiments. The internal diameters of extracted fresh porcine carotid arteries at pre- and post- PTDB dilatation
were measured. Balloon parameters were follows; pressure P=2atm, peak temperature in balloon T=60-80oC, and
heating duration t=4-30s. Morphological change in the media of dilated artery with PTDB were microscopically
examined with Weigert staining. Elastic properties were carried out by stress-strain measurements with calculation of
young's modulus. We found that PTDB dilatation provided the effect to prevent elastic recoil. We explained that the
reason of this effect might be arrangement of micro- structure in the media, i.e., heat-denatured collagen fibers sustained
the elastic recoil due to rubbery elastin fibers. The arterial elasticity was not significant different after PTDB dilatation.
It was suggested that there could be no compliance mismatch after PTDB dilatation in physiological range. We found
that a part of PTDB dilatation mechanism, in which the vascular wall structure played an important role. The optimum
operation parameters for PTDB might be determined in consideration of collagen denaturation progress and arterial
composition.
We studied Ho:YAG laser irradiation in blood vessel as a vasodilator ex vivo. We thought that the Ho:YAG
laser-induced bubble expansion might be able to dilate the vessel because we found the vessel wall expansion after the
Ho:YAG laser irradiation, that is steady deformation, in the vessel ex vivo. There have been many reports regarding to
the Ho:YAG laser irradiation in the vessel. Most of studies concentrated on the interaction between Ho:YAG laser
irradiation and vessel wall to investigate side effect on Ho:YAG laser angioplasty. We proposed to use the Ho:YAG
laser-induced bubble expansion as a vasodilator. We studied vasodilation effect of the Ho:YAG laser-induced bubble
ex vivo. The flash lamp excited Ho:YAG laser surgical unit (IH102, NIIC, Japan) (&lgr;=2.1&mgr;m) was used. The laser
energy was delivered by a silica glass fiber (outer diameter: 1000&mgr;m, core diameter: 600&mgr;m). The laser-induced
bubble was generated in the extracted fresh porcine carotid artery with the warmed saline perfusion. The laser energy
at the fiber tip was ranging from 170-1300mJ per pulse. Number of the laser irradiation was ranged from 20pulses to
100pulses. The outer diameter of the vessel was observed. To examine the change in mechanical properties of the
vessel wall, the stress-strain curve of the laser-irradiated vessel was measured. Birefringence observation and
microscopic observation of staining specimen were performed. When the laser energy was set to 1300mJ per pulse,
the outer diameter of the vessel after the laser irradiation was expanded by 1.4 times comparing with that of before the
laser irradiation and the dilatation effect was kept even at 10minutes after the irradiation. The elasticity modulus of
the artery by collagen was changed by the laser irradiation. In the polarized microscopic observation, the brightness of
the intimal side of the vessel is increased comparing with that of the normal. We think this brightness increasing may
be attributed to birefringence change by the arrangement of stretched collagen fiber. We suppose it is likely to be able
to use the Ho:YAG laser irradiation as a temporary vasodilater tool in spite of further study should be performed.
KEYWORDS: Birefringence, Collagen, Tissues, Scanning electron microscopy, Temperature metrology, Tissue optics, Microscopy, In vivo imaging, Arteries, Microscopes
Our photo thermal reaction heating architecture balloon realizes less than 10 s short term heating that can soften vessel wall collagen without damaging surrounding tissue thermally. New thermal balloon angioplasty, photo-thermo dynamic balloon angioplasty (PTDBA) has experimentally shown sufficient opening with 2 atm low pressure dilation and prevention of chronic phase restenosis and acute phase thrombus in vivo. Even though PTDBA has high therapeutic potential, the most efficient heating condition is still under study, because relationship of treatment and thermal dose to vessel wall is not clarified yet. To study and set the most efficient heating condition, we have been working on establishment of temperature history estimation method from our previous experimental results. Heating target of PTDBA, collagen, thermally denatures following rate process. Denaturation is able to be quantified with measured collagen birefringence value. To express the denaturation with equation of rate process, the following ex vivo experiments were performed. Porcine extracted carotid artery was soaked in two different temperature saline baths to enforce constant temperature heating. Higher temperature bath was set to 40 to 80 degree Celsius and soaking duration was 5 to 40 s. Samples were observed by a polarizing microscope and a scanning electron microscope. The birefringence was measured by polarizing microscopic system using Brace-Koehler compensator 1/30 wavelength. The measured birefringence showed temperature dependency and quite fit with the rate process equation. We think vessel wall temperature is able to be estimated using the birefringence changes due to thermal denaturation.
Various shape bubbles were generated by changing holmium-yttrium-aluminum-garnet (Ho:YAG) laser irradiation parameters. Intensive pressure waves induced by their bubble collapse were measured. The Ho:YAG laser-induced bubble in water-containing liquid had been reported by many authors regarding its shape and generated collapse pressure. However, controllability of the bubble shape and generated collapse pressure with various irradiation parameters has been still unclear. In our experiments, we changed the core diameter of optical fiber (400μm or 600μm), laser pulsewidth (FWHM 100-300μs or 50-120μs, depends on laser output energy), and positions of the optical fiber tip in a sheath. The bubble shapes were observed with the time resolved flashlamp photography. The expansion and contraction rates of the bubble volume were determined by the obtained bubble shapes. The collapse pressure was measured with a small diameter (0.5mm) calibrated hydrophone. The long Ho:YAG laser pulse irradiation made long shape bubble so-called "pear shaped" bubble. This pear shaped bubble generated low collapse pressure comparing to the spherical shape bubble which was generated by the short pulsewidth. Using the constant laser pulse energy, we obtained large volume bubbles with high collapse pressure by the optical fiber of 600μm core diameter. When the optical fiber tip was located in the sheath, the bubble expanded to the lateral direction, and then the high collapse pressure was observed along the lateral direction. Therefore, we could arrange the bubble shape by changing the irradiation parameters. We discussed the proper bubble shape for various intra-vascular applications.
We proposed new method of blood removal using Ho:YAG laser(λ=2.1μm)-induced water-vapor bubble to prevent distal tissue ischemia during angioscopic imaging. We successfully demonstrated capability of this blood removal method using blood-filled pocine coronary artery ex vivo. We used laser irradiation conditions of 200mJ in pulse energy and 2Hz in repetition rate. Ho:YAG laser for blood removal and flash lamp lighting for endoscopic illumination were irradiated in the porcine coronary artery through individual fiber optics. Timing of the flash lamp lightning of 2μs in duration was arranged to illuminate the maximum blood removal space, i.e. the laser induced water-vapor bubble. We successfully obtained intra-lumen view via a thin angioscope using the laser blood removal without using saline injection. We studied to determine the optimum laser-induced bubble formation which indicated the minimum invasion against the blood vessel. The time resolved photography in vitro, transient pressure measurement in vitro, and acute historogical study on irradiated vessel wall in vivo were employed for this determination.
KEYWORDS: Temperature metrology, Arteries, In vitro testing, In vivo imaging, Injuries, Animal model studies, Tissues, Laser irradiation, Laser therapeutics, Metals
We have been proposed novel short-term (<10s) heating balloon using the combination of light-heat conversion mechanism and heated contrast medium irrigation in the balloon to improve dilatation characteristics of balloon angioplasty. Our new balloon angioplasty had suppressed intimal hyperplasia in rabbit model. We designed following experiments to understand the mechanism of suppression of intimal hyperplasia in our new thermal balloon angioplasty. We also aimed to obtain the suitable heating condition in our angioplasty to suppress intimal hyperplasia. We studied influence of the short-term heating on smooth muscle cells (SMCs) lethality in vitro. We investigated number of SMCs reduction in media in order to prevent intimal hyperplasia. We applied to our heating balloon dilatation to chronic rabbit model using normal iliac artery to study relation between heating condition and hyperplasia suppression. We estimated temperature history of the rabbit vascular wall by thermal conduction calculation. We related the estimated temperature history to the hyperplasia suppression effect in the chronic rabbit model. Finally, we obtained the relation between number of SMCs decreases and intimal hyperplasia suppression. We obtained that the short-term heating with 10s laser irradiation corresponding to estimated temperature of 50°C in the media and prevented intimal hyperplasia in the rabbit chronic model. In this case, we estimated about 30 percents of SMCs cellular lethality in media.
We designed the method for prevention of restenosis after balloon angioplasty using laser-induced bubble-collapse acoustic wave. This study was performed to evaluate the effect on smooth muscle cells (SMCs) by Ho:YAG laser (λ=2.10μm)-induced acoustic wave, in vitro and in vivo. The laser energy was delivered by a silica glass fiber into water. Sound pressure was measured with a hydrophone changing the laser energy. The laser-induced acoustic wave was loaded to SMCs in vitro. This acoustic effect on SMCs was measured by MTT assay. The acoustic wave loaded SMCs were controllably injured with the laser energy and laser shots. The balloon denudated rabbit aorta was used to evaluate in vivo effect. The laser-induced acoustic wave loaded aorta was extracted at 42 days after the laser irradiation, and was examined by Hematoxylin-Eosin staining. We found that the laser irradiation of 20 pulses with 60mJ/pulse prevented SMCs proliferation. We think the mechanism of this effect might be same as brachytherapy. We demonstrated the applicability of Ho:YAG laser-induced acoustic wave against vascular restenosis after balloon angioplasty.
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