Photodynamic therapy utilizing a flush lamp pumped dye laser (504nm, 1 micro second of one pulse duration) and HpD was reported. Vx2 carcinoma transplanted on the abdominal wall of the rabbit was destroyed 0.6mm in depth.

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It is essential to understand the dynamic behavior of excited state of sensitizer in Photodynamic Therapy (PDT). Usually the Laser Flash Photolysis is applied for in vitro sample. We developed the system for measuring the triplet state behavior in the biological tissue²⁾.In this report,the system comprises conventional apparatus but makes special feature of fiber. We used a glass fiber which include monitor light guide and transient absorption guide, separately. To investigate of quench effects of oxygen, concentration of oxygen inhalation around mouse was changed. Concentration of oxygen inhalation affects little to the life time of triplet state.

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The phosphorescence properties, especially, their dynamic behavior of metal free and metal complexed porphyrins have been studied in saline containing 0 - 3 % human serum albumin(HSA). 6,7-Bisaspartyl-2,4-bis (1-hexyloxyethyl)-deutero-porphyrin (DP) and its galium (III) complex (Ga-DP), zinc (II) complex (Zn-DP), and indium (III) complex (In-DP) are used as photosensitizers.
In this paper, chemiluninescenc (CL) caused by photosensitization of porphyrins has been reported first time. Solution of porphyrins containing HSA more than 0.1 % upon irradiation cones to shots the phosphorescence tai th a lifetime longer than 1 ms of porphyrins concerned. with the increase in the irradiation time, the phosphorescence intensities and triplet lifetimes of porphyrins increase, depending upon their concentrations and triplet lifetimes and approach the saturated values close to those under deaerated conditions. The experimental results for phosphorescence and chemiluminescence may be interpreted in terms of anoxia in local environments surrounding the sensitizer induced by photosensitization. The cause of anoxia can be attributed to the reaction between serum proteins and singlet molecular oxygen generated by photosensitization of porphyrins.

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This study is concerned with the relations between the wavelengths and the penetration of the excitation light into tissue in tumor PDT. The following subjects are examined: (1) Absorption of organs; (2) relations between the energies and lifetimes of the lowest triplet states for porphyrins; and (3) possibility of two-photon excitation by Nd: YAG 1064 nm in PDT. The results obtained are summarized as follows: (1) The lengthening of the absorption wavelength of S₁-S₀ longer than 600nm is not necessary so; (2) the lengthening of the absorption wavelength results in the shortening of the triplet lifetime which leads to the decrease in the photochemical activities; and (3) two-photon excitation method is practically expected not to be effective in PDT.

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We studied the change of tumor blood volume at PDT using the reflectance spectrophotometer. The tumor (GCA to be established by serial implantation in our institute; adenocarcinoma papillo-tubulare) was implanted in the back of nude-mouse. When tumors became 1cm in diameter, HPD (10mg/kg or 50mg/kg) was injected intraperitoneally and then 48 horus after injection GVL or ADL of intense of 280 mW/cm2 was irradiated for three minutes.
The change of blood volume of tumors was determind by IHB and ISO using reflectance spectrophotometer, before and after laser irradiation.
At GVL was irradiated, increase of IHB and decrease of ISO were recognized. On the other hand when ADL was irradiated, the similar change of IHB and ISO was recognized but the degree of the change was less than that of GVL irradiation.
It is revealed by this study that the decrease of blood volume of tumors occurred in PDT. And this is assumed as one of the mechanism of PDT. The degree of change at GVL irradiation was superior than that of ADL irradiation, and then it is considered as one of the reason that GVL is excellent compared with ADL in PDT.

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Simple solvent system (Water-acetonitrile) utilization to reverse-phase (C18) HPLC analysis of hematoporphyrin derivative (HpD) showed high resolution. By this method, cellular uptake and elimination kinetics on HpD components with human gastric cancer derived cell line MKN-28 were investigated. Minor components, which were eluted just in front (31.2min) and behind (35.1, 35.7 and 40.6min) protoporphyrin (pp, 34.4min), showed marked accumulation and affinity with the cells. Whereas protoporphyrin, showing high accumulation, was rapidly eliminated from the cells as well as hematoporphyrin (Hp, 4.9 and 5.5min) and 2 (4) -hydroxyethyl 4 (2)-vinyl-deuteroporphyrin (Hvd, 18.4 and 19.7min).
The components except Hp, Hvd and PP were estimated to contribute 60% of the cellular photoactivation in vitro.

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In attempt to obtain basic data for endoscopical photodynamic therapy (PDT) combined with hyperthermia (HT), we studied the effects of the combination therapies using transplanted tumors.
We measured tumor volumes after four treatments, namely, PDT alone: HpD plus Argon laser irradiation (514.5nm) for 30 min, HT alone: Nd-YAG laser irradiation for 30 min, HT followed by PDT: HT for 15 min immediately before PDT for 15 min, PDT followed by HT: PDT for 15 min immediately before HT. The results indicated that mean tumor volume after PDT followed by HT was the smallest among the four treatments.
Using laser dopplar velocimeter, we measured blood flows of the transplanted tumors after PDT and HT. The results indicated that the blood flows after HT were significantly lower than after PDT.

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The morphological changes of the blood-brain barrier following laser hyperthermia were studied. Transmission electron microscope revealed swelling of astrocytic foot processes, endothelial infolding vacuoles and cytoplasmic swelling of the endothelium in and around the irradiated rat brain. Opening of the endothelial tight junction was not seen. We concluded that thermal effect of laser hyperthermia produced the swelling of the astrocytic foot process and endothelial infolding vacuoles. It was conceivable that the cytoplasmic swelling of the endothelium was caused by the specific reaction of the capillary endothelium secondary to laser irradiation.

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Early change of the blood-brain barrier (BBB) following laser hyperthermia was studied experimentally. Laser hyperthermia was applied to rat brains. Trypan blue was injected zero to ten minutes after laser irradiation. Fixed brains were prepared for macroscopic examination and detailed examination using image analyzer. On macroscopic examination the BBB started to open 6 minutes after laser irradiation.
However examination by image analyzer revealed that the BBB started to open 4 minutes after laser irradiation. Transmission electron microscopic examination disclosed no significant change in the capillary endothelium at 4 minutes after laser irradiation but showed endothelial infolding vacuoles and swollen astrocytic foot processes at 6 minutes after irradiation. We concluded that the BBB started to open 4 minutes after laser hyperthermia. The mechanism of the BBB opening following laser hyperthermia is probably due to the impaired endothelial membrane potentials.

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Our present experiments investigated on the effects of baloon laser thermia on normal intact gastric wall of 3 hybrid dogs. Dogs were surgically operated to expose gastric cavities, and a baloon filled with 15 ml, 0.25% Intralipid solution, was inserted inside the gastric cavity under anesthesia.
The pyloric region was exposed to laser irradiation for 20 min. at 42.5-43.0°C. One day after irradiation, erosion was observed in only a meager part of the mucous membrane. Although marked edema accompanied with slight hemorrhage and leukocyte infiltration were observed in the submucosal layer 1 and 2 days after irradiation, improvements in the edema with no hemorrahge were manifested 9 days after irraiation. No remarkable changes were observed in the propria muscularis. From the above findings, it was distinctly clear that baloon laser thermia did not elicit a significant side-effects on normal gastric wall.

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We have investigated the effects of local hyperthermia using Nd: YAG laser and shortwave radiofrequency. Groups of C3H/He mice transplanted tumors (Dunn osteosarcoma) were treated with local hyperthermia. Heating was performed for 15 minutes in laserthermia and 60 minutes in radiofrequency. After the treatment with each heating systems at 42.5-43°C, animals were subsequently sacrificed at 3 and 7 days. We observed the pathohistological and electron microscopical changes in the tumor cells and tissue. In spite of using different heating systems and treating different heating time, almost same tumor destructive changes were observed. These results suggest that hyperthermia is one of the effective treatment methods for osteosarcoma and in addition to heat, Nd: YAG laser energy may have another effect.

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The possibility of laser patch welding to the bronchus for the bronchial fistula was studied. The laser was delivered by the fiber. Comparatively good welding was obtained by contact method of CO laser to the surface of expanded-polytetrafluoro-ethylene (E-PTFE 0.2mm thick). The percent transmittance of CO laser through the 0.2mm E-PTFE was 35%. The strength of CO laser welding was roughly measured 16-18g under the condition of CO laser 400 W/cm2 7.5-10sec and 3mm ZnSe contact tip.

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We have carried out a series of experimental laparoscopic cholecystectomy in dogs (n=20). In our animal experiments, laparoscopic removal of the gallbladder was performed by Nd-YAG laser, ligating the cystic artery and cystic ducy with the clips used for vascular ligation. The irradiation of Nd-YAG laser for the ablation of the gallbladder using the bare quartz was done under 10-15 watts of output with 2,000-5,000J in total energy. Then, we have carried out a series of laparoscopic cholecystectomy in human (n=8) in same procedure. This procedure requires a comprehensive technical integration, such as the preparations of optimum instruments, excellent skills and the cooperation with surgeons. From the experience, it will be concluded that this poocedure has a greater advantage over the conventional open surgical methods, which surely promise the highly quality of life (QOL).

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We have already reported the endoscopic percutaneous observation and laser surgery in the subarachnold space and have shown the possibility that this type of endoscope could be a useful diagnostic and therapeutic tool. However, manageability of the tip of the endoscope was so poor that we felt it difficult to move the tip to a right place.
This time, we used an endoscope with bending ability of the tip and examined if this new function could improve the manageability of the endoscope. The endoscope (outer diameter 1.7mm) Includes 3000 image fibers, light guide and a lumen for a optical fiber for laser transmission and the tip can be bend by 20 degrees in two directions. We inserted this endoscope percutaneously via 13G epidural needle to an anesthetized goat and it was demonstrated that the bending ability of the tip considerably improved the area of observation and made it much easier to aim at for laser irradiation. We could cut a nerve root by laser irradiation (Xe-Cl eximer laser), carefully controlling the site of irradiation using this function. We conclude that the bending ability of the tip is important for the development of the spinal laser endoscope.

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We applied the laser irradiation on meniscus with the saline filled knee joint in order to prevent the several complication caused by the laser irradiation with the air filled knee joint. The experiment was made in vitro with the pig knee joint, with Ar⁺UV laser which we have regarded suitable laser for the arthroscopic laser meniscectomy, and with SiO₂ glass fiber which can deliver Ar⁺UV laser light. A pig knee joint was opened and ACL, PCL, MCL, LCL were cut off so as to expand the pig knee joint space. Under arthroscope contact irradiation on meniscus in saline using Ar⁺UV laser at the power density of 800 W/cm2 was done, and meniscus was perforated in several seconds irradiation. These experiment revealed that contact irradiation in saline using Ar⁺UV laser is useful for arthroscopic laser meniscectomy.

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The purpose of this study is to develope a arthroscope with laser for arthroscopic laser surgery. Methods: An original double monitoring arthroscope was developed which was composed of hard arthroscope with a lumen for flexible arthroscope. The flexible arthroscope had a lumen for laser fiber. The observation of joint space with hard arthroscope made possible to orient the access direction of flexible arthroscope. Then flexible arthroscope was accessed to the narrow space or the back space under the aid of hard arthroscope. After double monitoring observation. laser irradiation was done according to the therapeutic purpose of joint diseases. In this time, giant pulse Nd: YAG laser was used to investigate the possibility of laser joint sergery. Results: The system of double arthroscope was useful to observe the joint space in detail. And to cut, coagurate and vaporize were able to do. Conclusions: If we use this double arthroscope effectively. atraumatic joint surgery will become possible.

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A bipolar Nd-YAG laser handpiece was applied to dissect a mesenteric vein and lung of the mongrel dogs without threads and scissors.
An optimum dissecting power was 13W in the mesenteric vein and 15-20W in the lung.
The laser dissection was clearly achieved, and the bleeding and air leakage from the dissecting spot was not recognized. Pathological examinations revealed a tissue vaporization at the sandwiched portion between the two tips and a thermal fusion with remodeling around the tips. We concluded that the bipolar Nd-YAG laser handpiece would be practicable to dissect a tissue without threads and scissors.

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The efficacy of Excimer laser in coronary angioplasty (ELCA) has been reported in terms of its extremely precise cutting ability and minimum heat injury. The objective of this study is to compara multiple fiber Excimer laser system (AIS INC.) with bare ended Argon laser system (LASTAC, GV medical) using Watanabe Hereditary Hyperlipidemic (WHHL) rabbits.
This Excimer laser system has multiple silica laser fiber for over the guide wire method, and LASTAC Argon laser system has a baloon catheter for coaxial laser emittance. In the first in vivo study, the atheromatous plaque in a carotid artery was ablated transluminally (Excimer: pulse rate 20Hz, 35mJ/mm2, Argon; 5 watts, 2 seconds) and 90 minutes later the plaque was resected for histopathological analysis. In next in vitro study, the atheromatous plaque on the resected aorta was placed in saline, and laser energy was emitted perpendicularly on it (Excimer; pulse rate 20Hz, 2, 4, 6 sec, 35, 40, 45mJ/mm, Argon; 5 watts, 2 seconds). We obtained the following results: 1) Excimer laser ablated atheromatous lesion more clearly without heat injury and was more anticoagulative than Argon laser. 2) Multiple fiber Excimer laser vaporized only around the guide wire even in eccentric lesions. 3) Long Excimer ablation (4 and 6 seconds) caused acoustic and blast damage. We conclude from this study that Excimer laser is more preferable than Argon laser in coronary angioplasty, and it is importanat to selct a proper size of laser catheter, and the speed of catheter advancement in the target artery to avoid dissection caused by acoustic and blast damage.

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Using Nd: YAG (1.32μm and 1.06μm), Ho: YAG and Excimer (XeCI) lasers in 25°C air and 37°C normal saline, we measured perforation times and temperatures of human arterial walls obtained from cadavers.
The effect of Nd: YAG (1.32μm and 1.06μm) lasers on arterial walls was very limited. The perforation temperatures of normal arterial walls in 25°C air ranged from 72.5 to 103.0°C, and the maximum temperatures at a point 1.0mm from the perforation point in 37°C normal saline ranged from 41.4 to 62.0°C.
1.32μm Nd: YAG lasing for 5 seconds at 15 W in 37°C normal saline was able to penetrate an arterial wall of 2.0mm thickness with a calcified layer of 1.8mm. However other lasers were unable to change the same wall.
Thermal damage around the hole produced by Ho: YAG and Excimer in normal saline was insignificant.

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The laser probe with ceramic coating tip and the endoscope for this laser probe are being investigated as a system for visual laser angioplasty. The endoscope had two direction of bending function at the tip. The system was introduced experimentally through an antegrade pucture into the common cervical artery,in which occlusion was made with organized thrombus by the interposition of artificial graft and Nd: YAG laser could be irradiated to the organized thrombus through the ceramic coating tip under the visual field. The bending function of the endoscope improved the visual field inside the artery and also the good aiming ability was obtained. This system is thought to be applicable for some clinical use

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The animal experiment of CO laser angioplasty in vivo is described. The purpose of this study is the evaluation of guidance technology by the combination of angioscopy and angiography. A complete occlusion model at canine femoral artery was ablated by CO laser under this guidance system. The angioscope image was useful for the positioning of the ablation startpoint and also for the real time monitoring of the ablation depth. However, the simultaneous usage of angioscopy and angiography may be necessary to attain precise guidance in angioplasty procedure. The repetitive ablation procedures by CO laser contact irradiation made a large lumen comparing to single ablation procedure. The major experimental equipments which were employed in this study were the first trial products of the government supported angioplasty project.

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We have been studied to establish the requirement for the coronary laser endoscope with animal experiment using goats' coronary arteries by developing various coronary laser endoscopes. The purpose of this study was to develop coronary laser endoscope in which the tip had the bending function.
In this study, the laser endoscope with the diameter of 1.7mm which is thought to be applicable to the coronary artery, in which the tip had two directional bending function, was developed. The endoscope was evaluated with goat's carotid artery which was partially occluded with organized thrombus made by the interposition of Gore-Tex artificial graft.
The endoscopic view was very improved with two directional bending function of the tip, and excimer laser could be scanned in line to destruct the thrombus.
More than three directional bending function of the tip is required to improve the scanning ability of laser and is the most important next subject.

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During laser ablation, in order to prevent unexpected perforation and rupture of myocardium, it is important to be able to perform accurate irradiation and control the temperature of the irradiated myocardium.
We compared three method for laser ablation; the non contact method, the contact method with a ceramic probe, and a new contact method using a new contact probe developed. Left ventricules of 30 canines were irradiated using Nd: YAG laser.
The new contact probe consists of a 15mm hollow conical tube of poly vinyl chloride, with the hollow center filled with 0°Cwater and a tip is covered by poly vinyliden chloride.
The contact method is not suitable for laser ablation because of the much higher energy density and higher risk of rupture and perforation than the other two methods. The new irradiation method was considered to perform the same energy efficiency as the non contact method, and to allow more accurate and safer laser ablation than the existing method.

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Excimer laser endarterectomy (ExLE) was compared with conventional surgical endarterectomy (SE), about early response in atherosclerotic rabbit aortas and about late healing response in normal canine arteries.
In the first experiment, surfaces following ExLE were rougher than those after SE, but ExLE end points, without any intimal flaps, were smoother than those of SE exhibiting rough transitions and intimal flaps. And then thrombus formation in the ExLE was less than in the SE.
In the second experiment endotherial cells appeared at 3 weeks and completely covered surfaces at 3 months in the both techniques. But some of arterial walls following ExLE showed aneurysmal changes at 3 months.
In conclusion, it was demonstrated that ExLE exhibited no intimal flaps at the end points, lower thrombogenicity than SE, and favorable healing response. And so it is expected that ExLE will find a place in the future treatment of coronary artery disease.

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Angioscope-Fluorescence Analyzer System (AFAS) Which can be employed simultaneously as an angioscope together with real-time fluorescence spectroscopy has been studied in our laboratory. This study reports in vitro and in vivo Laser Angioplasty (LA) under AFAS diagnosis using a photosensitizer. Nd-YAG LA using a contact ceramic tip and in vitro AFAS diagnosis were performed on the aortas of sacrificed 7 athroscleotic rabbits (AR) which had been given Dehematoporphyrin ethyl (DHE), a photosensitizer, 24h before. The 72 sites of LA were histologically examined. Next, in vivo LA and AFAS evaluation were performed by alternately inserting the necessary catheter through the femoral artery in same treated 5 AR. Remarkable correlation (R=0.759) was observed between the residual intimal thickness after in vitro LA and 630nm fluorscence intensity. Fluorescence spectrums were devided to three type.“Type 1”has 630nm and 690nm peak pattern which is specific for DHE, and “Type 3” has 620nm and 670nm peak pattern”. Type 2 is medium type. “Type 3” site was in accordance with that of calcification of atherosclerosis. In the in vivo study, as the LA procedure progressed, DHE specific fluorescence decreased and disappeared when the media became completely exposed. AFAS can be a feedback diagnosis system for LA to prevent perforation of blood vessels.

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The irradiation effect for cadaver aorticwall athroma was studied using Q switched Nd: YAG laser pulse. Laser pulses were irradiated with repetition frequencies of 500-10KHz and maximum energy density of 80mJ/mm2 per pulse. The results were compared with those of CW irradiation (max. power 10w). Laser energy was emitted to the tissues within saline with contact condition. The evaporation of tissues with smaller thermal damage in peripheral region was observed for pulse irradiations compared with CW irradiation. Several conjunctures were proposed for the mechanism. The new type of quartz fiber at the end of which a specially designed lens-tip was welded,was prepared and the irradiation effect was discussed.

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The appropriate contact irradiation condition for CO laser angioplasty with a thin As-S glass fiber was studied. An ablation depth and coagulation thickness in atheromatous human aorta were investigated by changing duty ratio, frequency, and contact pressure. The fiber cable which is able to use clinically was composed of 200μm in diameter As-S fiber and 400μm in diameter CaF₂ contact chip. The power at the end of the fiber was adjusted to be 2W having sufficient safety margin. The higher contact pressure gave the better ablation efficiency. At the constant contact pressure 1kg/cm2 the best result for fine ablation with thin thermal damaged layer was obtained by the duty ratio of 20%and frequency of 1Hz.

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The authers have evaluated the selective accumulation of the tetracycline derivatives as photosensitizer to atheromatous plaque of the rabbit model. We detected the spectral properties of laser-excited fluorescence of tetracycline free base (Tc) and doxycycline (Dc; tetracycline derivative), taken up in rabbit aorta. Excitation source used is third-harmonic beam (355nm) of a Nd: YAG laser, whose imediated power and beam diameter are approximately 10μW and 100μm respectively. These photosensitizers were administrated to resected rabbit aorta in vitro or intravenously.
The result shows that each photosensitizer has the same fluorescent properties and accumulates selectively to atheromatous plaque in vitro. On the in vivo study, it is shown that doxycycline also accumulate selectively to atheromatous plaque, and a good selectivity can be taken from 6 to 12 hours after injection.
Furthermore, doxycycline also is one of the clinically used antibiotics, and thought to be a hopeful drug for clinical application of the PDT of atherosclerosis.

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This studies were performed on the possibility of safety making atherosclerotic foci regress with photodynamic therapy (PDT) using Hematoporphyrin Derivatives (HpD), as a photosensitizer. Atherosclerotic rabbits, whose atherosclerotic lesions in the aorta were induced by 2% cholesterol diet and by balloon damage, were divided into two groups, that is, group C and group H. The group C is consisted of rabbits nontreated with HpD and the group H treated with HpD. The argon laser introduced by fiber was irradiated on the athromatous lesion of abdominal aorta in vitro for 1sec-180sec, and the power was 100mW-2000mW. The aorta was dissected for histological study. Group H atherosclerotic lesions were vaprized by lower energy and shorter time level than in group C.
From the above data, it is suggested that PDT may be effective for treatment of atheromatous lesion of artery.

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To establish the method of coronary laser angioplasty by Argon laser, we have investigated factors preventing from complications of intracoronary laser ablations, such as perforations, coronary spasms and severe arrhythmias.
Laser ablations were carried out in normal canine coronary arteries under beating heart with bare-ended probe (BEP) and metal tip probe (MTP) of 1.5mm in diameter. Perforations were observed in all cases delivered above 10 joules of laser energy by BEP. In case of using MTP, neither perforation nor coronary spasm could be observed under the condition of within 20 joules of laser energy. However perforations were observed in 4 (15%) out of 26 cases delivered above 20 joules of laser energy.
Furthermore, percutaneous transluminal laser thermal ablations were carried out in normal coronary arteries of the living dogs to evaluate morphological response of coronary artery to the laser. Laser ablations were carried out at 28 sites under the conditions of 5 watts in output and 2 seconds in ablation time using MTP. If laser ablations were done at the left main trunk (2.5±0.3mm in diameter), no complication was found in all cases, On the other hand, if laser ablations were made at the portion of LAD (6) or Cx (11) (2.0±0.4mm in diameter), coronary stenosis induced by thermal constriction was observed in 2 (12%) out of 17 cases. From these findings, MTP of 1.5mm in diameter should be applied for the coronary artery of which diameter is 2.0mm or more to avoid thermal vasoconstriction of the coronary artery.

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Percutaneous transluminal laser angioplasty was carried out for 46 patients with peripheral artery disease. Consequently, initial success was achieved in 46 (77%) of all 60 lesions, (25 [86%] of 29 in the stenotic lesions, 21 [68%] of 31 in the occlusive lesions). These were no complications required emergency operation. The cumulative clinical patency rate was 87.5% in 39 cases with the clinical success (95.2% in the 22 stenotic lesions, 76.9% in the 17 occlusive lesions). Thus, laser angioplasty was safe, and effective to increase the initial success rate for lesions that were difficult to treat by conventional balloon angioplasty. This new technique might perform further clinically application by reducing re-stenosis and improving the patency rate.

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Laser has been widely utilized in the field of cardiovascular surgery. Since 1980 we have employed CO₂ or Argon laser for creating transmyocardial revascularization and making vascular anastomosis as well as performing laser angioplasty. In this study-vascular anastomosis by laser was investigated experimentally and clinically. Subsequently, optimal conditions for vascular ananstomosis were 20-40mW in output and 6-12 sec/mm in irradiation time. Based on the excellent experimental studies laser was clinically employed for 108 patients with intermittent claudication and anginal attack as well as tissue ischemia. Anastomotic sites were located in the femoral-, and the tibial arteries, the radial- and the brachial arteries as well as the coronary arteries. The longest follow-up period is now 5 years 9 months after laser surgery. They are doing well, except for 1 case who had tiny hematoma after body exercise. Thus, an availability of vascular anastomosis by laser could be recognized.

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Contact laser thermal angioplasty with a metal hot tip heated by Nd-YAG laser system (Trimedyne Inc.) was performed on 18 arterial stenotic regions in 12 patients, and 13 arterial occulsive regions in 13 patients.
Intial angiographic and clinical success was achieved in 17 of 18 (94%) stenotic regions, 4 of 13 (31%) occulusiv regions.
It was satisfactory result that laser angioplasty was performed on short stenotic regions, but it was difficult that it was performed on long occulsive regions below superficial femoral artery.

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The percutaneous transluminal coronary angioplasty (PTCA) is currentry a widely accepted procedure in the treatment of patients with obstructive coronary artery disease. However, it is associated with the occasional occurence of abrupt closure and the relatively high incidence of restenosis in initially successful cases. To alleviate major factors that appear to contribute abrupt closure and restenosis (thrombogenic surface, dissection, arterial recoil), laserthermal angioplasty was considered to be effective to seal dissections and “weld” dissected atherosclerotic plaque back to the underlying vascular wall. We developed a “hot balloon” angioplastic catheter with use of argon laser thermal energy source to address these problems. As the“hot balloon”is made of teflon, the heat resistance is high. The deflated balloon catheter was inserted in extracted porcine coronary artery and inflated. When the balloon pressure reached 3 atm, 3-6W of argon laser was irradiated for 30-60 sec. When 6W energy was delivered, the balloon temperature reached 100°C within 15 sec and then adventitial temperature was below 40°C.Intimal flap and separated vascular tissue were fused without evidence of thermal effect on adventitia and extravascular tissue. This study indicate the potential role of“hot balloon”angioplasty should be effective in the treatment of important causes of restenosis.

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We studied the dose-response of focal gastric mucosal blood flow measured by laser-Doppler flowmetry. Lase-Doppler flowmetry measured a dose-response relations for the increase in blood flow of rat's gastric mucosal blood flow receiving endothelin. Endothelin-induced responses of gastric mucosal blood flow of rats consited of three phases, that is, a rapid and transient decrease phase and then transient increase following a long lasting decrease (2000 pmol/kg). Laser-Doppler flowmetry is useful technique for evaluating focal gastric mucosal blood flow in rats after intravenous administration of Endothelin.

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The blood flow measurement with an apparatus utilizing the laser speckle method has enable us to image the blood flow in gastric mucosa. Therefore, a blood flow change with time can be observed easily by the comparison between image of blood flow. There is a correlation between the laser speckle method and the laser doppler method. This method of measuring blood flow is thought to be useful in the future studies of the blood flow in gastric mucosa.

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Experimental study is conducted on the sensitivity of the Laser Speckle Flowgraphy to the velocity of the moving scatterers. A rotating ground glass plate is illuminated by a laser line spot and is imaged onto a line sensor. The average difference of two successive scannings is calculated and plotted as a function of the velocity of the ground glass plate. It is shown that the average difference used as a unit of the flow level in the Laser Speckle Flowgraphy is linearly proportional to the velocity of the plate within a certain range of the velocity.

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A method is studied for measuring the blooflow in retinal vessels using laser speckle phenomena. The intensity fluctuation of speckles scattered from red blood cells in a retinal vessel is detected in the magnified image plane, and analyzed by the photon correlator which gives us the relative velocity of the blood flow. The experiments were performed to evaluate the bloodflow velocity in a glass capillary and in the retinal vessels of a rabbit and human volunteers. The results show that the bloodflow in retinal vessels can be measured by using laser speckles.

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The laser speckle method is studied for evaluating the blood flow in retinal vessels of human subjects on the basis of the photon correlation technique. In order to treat effectively the photon correlation data, we improved the apparatus for signal analyses. The experimental results show that the present method is useful for measuring the temporal fluctuations of retinal blood flows.

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We developed the apparatus for measuring the retinal blood flow using laser speckle based on the photon correlation technique, In this paper, we performed the four different experiments for human volunteers by using this apparatus. The experimental results show the usefulness of the method for measuring 1) the retinal blood-flow volume, 2) the variation of the retinal blood flow due to oxygen breathing, 3) the pulsating blood flow in retinal arteries, and 4) the variation.of the retinal blood-flow volume due to photocoagulation.

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We have been studying the essential physiological role and fundamental characteristics of biophoton emission, which is the ultraweak light emission from almost all biological systems in various living states and considered to be an universal phenomenon occurring in nature. In this paper, we report, with several examples of experimental results including emission spectra, the detailes of methods and techniques developed for highly sensitive measurement and analysis of spontaneous biophoton emission originating from the surface of human body.
The data obtained for the first time indicated that the intensity levels of ultraweak emission, measured at the tips of left hand index and middle fingers, show a variety of individual differences, reflecting dynamic physiological states in the subjects. It was actually found that the variation in emission intensity is closely related with, for example, the activity of the thyroid gland. In addition, a periodical trend similar to circadian rhythm was reproducibly observed in the variation of emission intensity measured at the left hand fingers.

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We describe here the study of biomedical measurements utilizing spectral analysis of ultraweak photon emission from human blood plasma and urine. It has been suggested that detection of ultraweak photon emission intensity of plasma, urine or other kind of biological materials provides information regarding to physiological condition of vital system; especially it reflects the states of oxidative stress of the body. In this experiment, we characterized emission spectra of plasma and urine, and examined the comparison between those from hemodialysis patients (HD) and normal subjects. In addition, the spectral properties of isolated serum lipoprotein were studied. Spectral analysis was carried out by the filter-differential type biophoton spectral analyzer covering the wavelength region of 450-850nm.
In the experimental results, spectral change of normal plasma was observed at the auto-oxidation process, with prominent emission peak around 670nm. Difference of spectral distribution between HD and normal subjects was observed at 400-700nm region, and significant difference appeared at 600-700nm region. It is suspected that this wavelength region represents the states of oxidative stress of the body significantly.

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This paper reports and discusses, we believe for the first time the achievement of laser absorption computed tomography for actual in vitro biological objects using Coherent Detection Imaging(CDI) method. This CDI scheme offers the feasible and reliable means for optical computer-assisted tomographic imaging based on the optical heterodyne technique with lasers that has very high sensitivity and excellent directivity to distinguish one specific direction from another in highly scattering absorptive media. We have experimentally demonstrated the fulfillment of three fundamental conditions for the establishment of laser absorption tomography to establish the CDC method.

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This paper reports, we believe for the first time, the basic principle and experimental demonstration of differential absorption computed tomography of Coherent Detection Imaging(CDI) method. Although the CDI scheme offers the feasible and reliable means for optical computed tomographic imaging of in vitro/in vivo biological objects based on the optical heterodyne technique incorporating laser beams, the single laser beam method is difficult to distinguish or to eliminate apparently detected absorption due to multiple scattering from actual absorption distributed inside the object. In order to solve this problem, the differential absorption technique employing the two different-wavelength beams is practically usefull. We performed the experiment using glass phantoms along with red and green beams simultaneously genarated from a He-Cd laser.

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Experimental results of optical measurement of action potential in the ventricle of a carp and optical properties of WW781 which is a voltage-sensitive dye are described. The ventricle was removed from the carp and stained with a solution of WW781. The spike phase of the ventricular action potential was recorded by the optical method. The fluorescence emission was increased about 5% by the action potential. The absorption and fluorescence emission spectra of the solution of WW781 were measured. According to the fluorescence emission spectra obtained from several staining periods, it is necessary about 30 min. for the staining period in order to obtain large fluorescence emission.

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The object of this study is to develop a new system to measure optically the spred of electrical activation wave in heart (multisite measurement system).
The optical changes due to action potential is very little and is influenced by motion artifact. Our attempt to suppress the motion artifact is p harmacologic method. Ca2+-free solution suppresses the musle contraction. In fluorescent signals of WW781 on whole carp's veniricu I bathing Ca2+-free solution, we confirmed suppression of artifact and delay of electrical activation wave in four point.

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We examined fluorescence spectrum on HpD treated cultured and excised lung tumor and normal cells. Cultured and excised lung tumor cells have two peaks of fluorescence but normal lung cell have no fluorescence. The fluorescence of HpD solution results suggest shorter peak of fluorescence derive from HpD polymer.

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Rabbit stomach walls were measured by the fiber-optic pulsed photothermal radiometry(PPTR) technique in vitro and in situ. The PPTR technique is one of radiometry techniques of which absorption, thermal diffusivity, and a layer structure of sample can be measured. We developed novel fiber-optic PPTR apparatus to apply this technique for endoscopic diagnosis. The PPTR waveforms which were obtained from proper muscle layers indicated shorter 1/e decay time than that of mucosa. Simultaneously, a diagnosis of layer structure was suggested by the PPTR waveforms from in vitro. This PPTR technique expected to be applied for endoscopic cancer diagnosis. Further study is necessary, for this purpose.

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