A Pulsed Dye laser together with specifically designed integral ball-tipped optical fibres have been used for the primary recanalisation of femoropopliteal vascular disease in 25 limbs of 23 patients. All patients had complete occlusions of the vessels ranging from 8-49cms in length (mean 22cms), having presented with critical ischaemia (18) or severe claudication warranting operative intervention (5). Pedal ulceration was present in 8 limbs and digital gangrene in 4. The laser produced visible light at 480nm in lOOmJ/lus pulses, at a frequency of 10-20Hz. The energy delivery device comprised a smooth atraumatic ball-tip constructed from the glass of the optical fibre, which was loaded retrogradely into a standard balloon angioplasty catheter. The device was introduced through a common femoral artery cutdown. Angiographic recanalisation was achieved in 22 of the 25 limbs with a mean energy of 280J(range 68-727J) and in each case the channel created by the laser fibre was augmented by balloon angioplasty. Technical failure occurred in three cases, caused by a wall dissection, persistent side-branch entry and incomplete lesion penetration respectively. Eighteen of procedures (72%) were clinically successful with marked symptomatic improvement. Of the four angiographic successful but clinical failures, acute occlusion within 48 hours occurred in 2 diabetic patients with very poor run-off and distal gangrene. The third case failed acutely due to a technically inadequate balloon dilatation and the fourth patient failed to improve symptomatically due to widespread with segmental tibial vessel disease below a successful recanalisation. Over a mean follow-up period of 7 months, three patients died of myocardial infarction. Twelve of the 23 patients (52%) remain well with patent vessels. These early results demonstrate the efficacy of pulsed dye laser angioplasty using ball-tipped optical fibres.

We present the results of 12 XeC1 laser coronary artery endarterectomies performed in 10 patients during CABG surgery. The results are very encouraging and led us to the developement of a new and more efficient laser catheter &livery system which is described in the second part of this paper.

Two hundred ten percutaneous excimer laser coronary angioplasty cases have been done using a XeC1 excimer laser system operating at 308 nanometers. The overall results of the cases are encouraging. The acute clinical success rate is approximately 85%,with a low rate of complications.

Results and operative problems of excimer laser angioplasty in human arteries will be presented. They pertain to a clinical experience about the coronaric district in association with A.C. by-pass procedure and in the iliac and femoralpopliteal districts with a percutaneous approach.

Argon ion laser endarterectomy has progressed from the laboratory to a clinical trial for peripheral vascular disease and now to a clinical trial for carotid artery disease. In the first 18 months of clinical trials, 14 peripheral laser enarterectomies and 4 carotid laser endarterectomies were performed. Low power argon ion laser radiation (1.0 W) was used for all operations. The peripheral vascular reconstructions resulted in symptomatic relief and all carotid patients are neurologically intact. There were no arterial injuries from laser radiation and all arteries showed smooth endarterectomy surfaces with welded end points. The initial clinical studies show that laser endarterectomy can be used for carotid artery disease as well as peripheral arterial disease with low power argon ion laser radiation.

We performed a clinical trial to evaluate the safety and efficacy of a unique lensed-fiber delivery system with a pulsed Neodymium-yttrium aluminum garnet (Nd-YAG) laser in patients with atherosclerotic peripheral vascular disease. The lensed-fiber consists of a spherical silica lens, 1 .5 mm in diameter, mounted at the distal tip of a 300 im silica optical fiber. The Nd-YAG laser is pulsed at 10 Hz, and we delivered 0.5 J/pulse with a pulse duration of 100 msecs in 2- to 5-second bursts. Successful recanalization of stenoses or occlusions was obtained in 9 of 10 patients and was manifested by improvement in blood flow as measured angiographically and with ankle-brachial blood pressure index improvement (> 0. 15). There were no arterial perforations or dissections associated with the laser angioplasty. All successfully recanalized patients required adjunctive balloon angioplasty to obtain a satisfactory reduction in luminal diameter stenosis of the treated artery. We conclude that this unique delivery system and the pulsed Nd-YAG laser are a safe and effect method of recanalizing arterial stenoses not amenable to conventional balloon angioplasty alone.

Percutaneous transluminal laser angioplasty with a pulsed Nd:YAG laser (1,064 nm wavelength, 100 jig pulse duration, up to 0.4 J per pulse, 10 Hz repetition rate) coupled to optical fibers with sapphire tips of 1.8, 2.2 and 2.9 mm diameter was performed in 17 chronic occlusions of iliac, femoral, popliteal and fibular arteries in 15 patients. Clinically the procedure was successful in 14 cases. The probe formed a primary channel of at least 2.0 mm width which was further dilated by conventional balloon catheter. Ankle/brachial systolic pressure index (ABPI) increased from 0.46 0.13 to 0.84 0.21 after the procedure. Two failures were due to an extensive dissection which occurred after balloon angioplasty and resulted in an early reocclusion. In the remaining case a balloon catheter could not be introduced through the 30 cm long primary channel which reoccluded shortly after the recanalization. The initial patency rate was 82 % and in 5 patients followed for more then 6 months the ABPI showed only a minor decrease. These first results are encouraging and it is likely that this method could become an important alternative to conventional balloon angioplasty.

As the lead paper for the session describing new results in the application of fiber optic systems to invasive treatments and surgery, this paper presents an overview of the basic properties of optical fibers and the advantages of using them in such applicaticns along with the challenges and problems which need to be addressed in designing the systems.

The laser has established a strong position in the field of tumor surgery. The endoscopic modalities of tumor coagulation in particular have been developed so far, that in some cases even tumors in anatomically difficult locations or inoperable tumors can be coagulated interstitially. The Nd:YAG laser is well suited to this technique due to its good coagulation properties and the transmissiblity through flexible fibers. Application systems such as the bare fiber, the diffuse emitting fiber, the frosted sapphire tip and a newly developed circumferentially emitting fiber, the so-called ITT light guide, differ widely with respect to beam characteristics, power density at the fibertissue transition, maximum laser power, geometrical dimension, flexibility, adhesive properties and compatibility with MRI diagnostics and MRI therapy control. In vitro experiments as well as first results from animal trials and clinical experiments prove that the Nd:YAG laser and the new ITT light guide provide a simple and reliable technique for interstitial thermo therapy.

In recent years laser technology has undergone a tremendous development. New laser sources have become available for routine applications which are now being introduced in various fields of medicine. In particular, excimer, pulsed dye, new solid state (Er:YAG, Ho:YAG, Alexandrite) and diode lasers exhibit promising characteristics in view of therapeutic procedures. At the same time optical fiber technology has been constantly ameliorated, primarily due to the growth of the telecommunication needs. Thanks to the manufacturing quality and to new types of optical fibers, it is now possible to transport through fibers the high power or energy which is often necessary to achieve therapeutic effects. As these fibers can have a thin diameter, new possibilities of treatment are being offered in that the laser beam can be brought inside the human body through natural openings or small incisions, thereby rendering more invasive procedure unnecessary. In this paper some aspects of power and pulse transportation characteristics of optical fibers are discussed and results of corresponding experiments are shown.

The transmission properties of fused silica fibers irradiated by high power high repetition rate XeC1 laser have been investigated. Laser-induced additional losses of radiation were measured as a function of intensity and of repetition rate.

Overview of the development in crystalline infrared fibera and hollow waveguides is made for the practical use of the last resialts in applications of the cables based on these fibers and waveguideB.

The development of specialized fiber tips, tapered fibers and fiber bundles for the XeCl excimer laser recanalization of coronary arteries during open heart surgery is described.

Advanced laser operational techniques have been introduced using the Nd:YAG or the argon laser in combination with fiber techniques and contact probes . In gynaecology, for exantple, surgeons need highly flexible fiber transmission systems for laparoscopic operations 2 Indications such as adhesiolysis or endornetriosis can be treated without mechanical traumatisation and bleeding using the laser light. Laser systems with different wavelengths, fibers and tips have become a very flexible surgical instrument. Feedback control of the reaction of the laser light with tissue makes the inedical laser system save and reliable.

There are currntly several methods in the field of laser lithotripsy which operate not only at different wavelengths and pulse lengths but also with various types of optical front ends and various irrigation fluids'6. The methods can be divided into two main groups: First, those which utilize stone absorption and plasma formation on the stone surface to initiate stone fragmentation, such as dye lasers. Second, those which generate shock waves and caviatation in the surrounding fluid and which require additional means to produce aplasma (e.g. irrigation, focussing fiber end or metal surfaces). The pulsed Nd:YAG laser belongs to this group. The method presented here is the double pulse technique which is a combination of both methods. It uses two laser pulses with a short time delay transmitted by means of a fiber to destroy body concrements. The first pulse is the first harmonic of the Nd:YAG laser (532nm) which improves the coupling efficiency of the laser radiation with the stone. The second pulse is in the fundamental mode of the laser (1064 nm) delivering the high energy for the stone disruption.

Th space irradiance produced by a fiber with a cylindrical diffusing tip was measured under a variety of launch and mode miling conditions. The aim of these measurements was to determine the extent to which conditions of use would effect the light distribution and to assess the impact these variations in light distribution would have on the therapeutic effect when the fibers were used in Photodynamic therapy treatments.

The uniform distribution of light over the area to be photodynamically treated is one of the prerequisites for a successful tumor therapy. For homogenization of laser light distributions especially in hollow organs a new method has been developed. It applies fiber coupled emitters in combination with a highly backscattering layer deposited on the inner wall of the organ to be irradiated. The effect of homogenization by means of this layer has been calculated for spherical and cylindrical hollow organs and compared with experimental results. This method also seems to be applicable for organs with irregular geometry. Laser light applications for different medical fields will be described. Applying the same method, isotropic light detectors with diameters of less than 1 mm have been developed for irradiation control during photodynamic treatment or for determination of light distributions in tissue.

Four ways of optimizing laser-assisted treatments in hollow organs are proposed in this paper: 1 . For coagulation in axial direction at small irradiation distances fiber tips with enhanced divergence increase the coagulation volume and reduce vaporization. 2. Circumferentially complete coagulation of cylindrical organs can be achieved by using a radially radiating probe. 3. Radiators for photodynamic therapy in cylindrical organs can be constructed and optimized by means of a theoretical scattering model. 4. Isotropic radiators based on conical fiber tips improve the radiation into the rear hemisphere.

Contact fiberoptic surgery has been an important step in the evolution of modern day laser surgical procedures. Synthetic sapphire tips, attached to the end of a surgical fiber, are an accepted modality. Sapphire tips optically mold the distribution of the lasers energy exiting the fiber. New developments in quartz fiberoptic tips have provided surgeons with similar tissue results as sapphire tips, with greater flexibility, decreased size, and reduced cost. A pilot study was conducted at the Western Institute for Laser Treatment utilizing these quartz fibers in research and progressing into clinical procedures. The development was through a laser peripheral company; Laserguide Inc.

In the medical field of laser light application detector systems are required for measuring the light power applied to the tissue and monitoring instabilities caused by the delivery system during the application of the laser light. An isotropic detector was developed consisting of a fiber tip molded to a sphere and covered with diffuse backscattering layers. The homogeneity of the isotropic detection is 85-90% in an angular field of Additionally a monitoring device has been developed which consists of a darkened chamber holding a part of the fiber bent to a curve. Integrated photodiodes detect the photons "stepping" out of the fiber. Defects of the fiber, the fiber tip, changes in the medium around the fiber tip, and variations of the laser output have influences on the detector signal. Both devices could be useful in evaluating an exact dosimetry for light.

Most catheter based oximeters use optical fiber to deliver two M more colors of light to the blood and collect the reflected lights with another optical fiber. Oxygen saturation of the blood is calculated from intensity of the returned lights. The coupling efficiency of this type of two-fiber sensor depends on the separation of fibers, the numerical aperture (NA) of the fibers, and the launching condition of lights from LED's to the transmission fiber. A micro-optical integrator was designed to combine outputs from two LED's into a multimode step-index fiber pig-tail through a high NA microball lens. The mismatch in the modes of propagation between red and IR lights was corrected by looping and sine-wave bending the fiber before it was coupled to an NA limiting GRIN lens, which also serves as an exit window. A far-field scan of two lights shows these two lights have spatial overlap of 92% or better. The overlap at the tip of the catheter, after it was coupled to the mode mixing pig-tail, is better than 98%. The addition of this simple method of mode-mixing has improved the overlap by nearly 30% and has substantially improved the accuracy of the oximeter, especially when in vitro calibration is used before taking the measurement in blood.

A method was developed to measure 02-saturation and Indocyanine-green concentration without external haematocrit correction by recording reflection spectra with a fiberoptic catheter and a CCD array camera, connected with ap-computer. The calculation is based on evaluation of the whole spectrum. Thereby it was shown that it is possible to determine Indocyanine-green and O2-satrati0n and to correct the haematocrit using three wavelengths instead of two wavelengths as usually done. The calculation differs from conventional methods not only in the additional wavelength, but also in the bandwidths used. When compared with extracorporal photometric transmission reference techniques the correlation coefficients of O2-saturation are r=O.996 (n=67) in vitro and r=O.993 (n=267) in vivo, and the coefficients of Indocyanine-green are r=O.996 (n=87) in vitro and r=O.998 (n=107) in vivo. In comparison with the same reference technique, a conventional commercial fiberoptic reflection photometer (IVH3, Fa. Schwarzer, MUnchen, Germany) using LED's at two wavelengths and requiring haematocrit correction showed somewhat poorer linearity and correlation coefficients. [ Indocyanine-green, in vivo r=O.995 (n=96); 02-saturation, in vivo r=O.976 (n=92) I

The skin erythema meter is a fibre-optic, dual wavelength reflectance meter which measures the reflectance of the skin on two wavelengths, one the blood/haemoglobin absorption band (555 nm) and another a reference (660 nm). The instrument consists of a fibre-optic sensor head, a microprocessor-based control and analysis unit and a plotter, and it presents the relation between the measured reflectance results in terms of a reflectance index (R(555nm):R(660nm)). The measurement cycle, including printing, takes 5 seconds. Stability tests on the erythema meter (constant distance, reference object) showed the standard deviation of the reflectance index to be +/- 0.1%, while that in repeatability tests was <+1- 0.5% for skin and <+1- 0.2% for paper with hand-held positioning and repetition. The dynamic change in the reflectance index was about 30% with strong irritation. Results of various irritation test series on human skin are also presented. Finally, the performance and applicability of the skin erythema meter with respect to allergy test procedures, irritancy testing and measurement of UV-induced erythema are discussed.

An infrared fiberoptic multichannel radiometer was used for monitoring and controlling the temperature of samples in a microwave heating system. The temperature of water samples was maintained at about 40 °C, with a standard deviation of ± 0.2°C and a maximum deviation of ± 0.5°C. The temperature was monitored on the same time at several points on the surface and inside the sample. This novel controlled system is reliable and precise. Such system would be very useful for medical applications such as hypothermia and hyperthermi a.

Fiber-optic sensors based on a controlled-release polymer provide sustained release of indicating reagents over long periods. This technique allows irreversible chemistries to be used in the design of sensors for continuous measurements. The first reported sensor used 8-hydroxypyrene- 1 ,3,6-trisulfonic acid and sulforhodamine 640 to measure pH continuously for three months in the range of 5.5 to 8.0 with a precision units. The sensor reported in this paper is based on a fluorescence energy transfer immunoassay. The sensor was cycled through different concentrations of antigen continuously for 30 hours. Although the sensor was not optimized, the data indicates the viability of the technique.

A ratiometric pH-sensitive fluorescent dye (hydroxypyrenetrisulfonic acid) was covalently attached to an acrylamide polymer. These pH-sensitive copolymers were either covalently bonded to the end of an optical fiber or polymerized into separate gels. Long-term, accelerated aging studies were performed on the fibers and gels in 43°C distilled H20. The fiber-immobilized optrodes gave good pH responses for up to 2 months. The pH-sensitive gels were physically attached to optical fibers and gave very good pH responses for over one year. These physically immobilized, one-year-old, pH-sensitive copolymers provided optrodes with linear pH responses between pH 6 and 8 and resolution greater than 0.25 pH unit. A simple photostability experiment on these optrodes showed that they were very photostable. The results of this study indicate that pH-sensitive copolymers in a simple optrode design can be employed as pH sensors with useful lifetimes exceeding one year.

The purpose of the fluorescence and Raman experiments in this study is to identify the cause of the red shift in the observed fluorescence emission of coronary arteries after laser ablation. In addition the identity of the molecular bonds broken in the photoablation process has been probed. These identifications are necessary, if one is to understand the laser tissue interaction and to monitor this interaction in a laser angioplasty procedure.

A significant clinical problem in the local treatment of cutaneous metastases of breast cancer (by any modality--surgery, radiation therapy or photodynainic therapy) is the fact that the disease almost always extends beyond the boundary of visible lesions in the form of microscopic deposits. These deposits may be distant from the site of visible disease but are often in close proximity to it and are manifested sooner or later by the development of recurrent lesions at the border of the treated area, thus the "marginal miss" in radiation therapy, the "rim recurrence" in photodynamic therapy, and the "incisional recurrence" following surgical excision. More intelligent use of these treatment modalities demands the ability to detect microscopic deposits of tumor cells using non-invasive methodology. In vivo fluorescence measurements have been made possible by the development of an extremely sensitive fiber optic in vivo fluorescence photometer. The instrument has been used to verify that fluorescence correlated with injected porphyrin levels in various tissues. The delivery of light to excite and detect background fluorescence as well as photosensitizer fluorescence in tissues has been accomplished using two HeNe lasers emitting at 632.8 nm and 612 nm delivered through a single quartz fiber optic. Chopping at different frequencies, contributions of fluorescence may be separated. Fluorescence is picked up via a 400 micron quartz fiber optic positioned appropriately near the target tissue. Validation of these levels was made by extraction of the drug from the tissues with resultant quantitation. Recently, an extensive study was undertaken to determine if fluorescence could be used for the detection of occult, clinically non-palpable metastases in the lymph node of rats. This unique model allowed for the detection of micrometastases in lymph nodes using very low injected doses of the photosensitizer Photofrin II. Data obtained revealed the ability to detect on the order of 50-100 cells using 0.25 mg/kg of sensitizer, a level 20 times lower than normally used for treatment of animal tumors. These results indicate that Photofrin II could be used for fluorescence detection of small metastatic tumors, while substantially reducing the major side effect of PDT; namely, prolonged photosensitivity. Results to be presented demonstrate the ability of this technique to detect microscopic deposits of malignant tumor cells in patients with metastatic breast cancer. These deposits were found in clinically negative areas of the chest wall.

The introduction of fiber optics together with lasers has opened up many new areas of medicine, and in the case of the Fluorescent Fiber Optic Probe (hereafter Probe) make it possible to more selectively detect photosensitive drugs bound in tissue. In this case the fluorescent marker was formerly hematoporphyrin derivative (HpD), and has recently been inrnroved and replaced by dihemnatoporphyrin ether/ester (DHE) . ornmercially the drug is available under the trade name of Photofrin II Due to the small and flexible nature of the fibers themselves, fiber optics are an ideal tool to deliver and detect light through the biopsy channel of many commonly used endoscopes. In the case of the Probe a krypton laser operating in the violet region of the visible spectrum (406. 7 (36%) , 413 . 1(60%) , 415. 4 (4%)nm) is used as the exciting source to take advantage of the strong absorption peak of DHE around 410 nm. By monitoring the level of tissue autofluorescence (570 nm) and DHE fluorescence (690 nm) we are able to provide an output to indicate those areas where the fluorescent marker drug is localized while correcting for large variations in the fluorescence signal due to distance changes. Distance variations of the detecting fiber from the source are corrected for by ratioing the level of the two individual fluorescent signals received to provide a relatively linear fluorescent output reading with respect to individual channel readings and distance. The Probe is also designed to detect fluorescent drugs bound in tissue while working in the presence of the white light source used in endoscopy. The probe together with its own exciting light source (krypton laser) works as a stand alone device and does not require any modification or interlock with existing endoscopic equipment. Only the use of the biopsy channels of the endoscope are needed to insert the optical pick-up and delivery fibers.

A fiber-optic laser light-scattering system (FLS) for measuring ciliary function was evaluated by means of three sets of in vitro experiments. First, FLS performance was compared to that of a previously proven benchtop laser system (BLS). Using tissue excised from rabbit fallopian tubes, ciliary beat frequency (CBF) of each sample was measured with FLS and BLS. Paired CBF measurements showed excellent correlation between the two systems (r =0.93). Second, the FLS was used to evaluate the dependency of CBF on temperature (T) by using tissue sampies of rabbit oviductal fimbna. Regression analysis of CBF vs T showed a linear relationship over the range of 18-37°C for both individual samples (r =0.98) and pooled data from all experiments (r = 0.84). Fmally, the relalionship between CBF and ciliary ovum transport rate (TR) was tested by using T to modulate CBF of rabbit fimbria, in vitro. The relationship was linear over the range of CBF from 10 to 30 Hz (r2 = 0.83). At 37°C, CBF = 31±1 Hz, and TR = O.12±.02 mm/sec. equal to ovum transport rate in situ. The FLS is a valuable tool for characterizing ciliary activity and thus ovum transport function. Owing to the fact that ciliary dyskinesia resulting from disease of the fallopian tube is associated with infeitility, the FLS may be useful to acquire data important to the clinical evaluation of fallopian tube function and female infertility.

The dosimetry with glass fibers perrilits for the first time the dose to be determined in the immediate vicinity of the tumour. A fiberoptic dosimeter can either be introduced during an operation or else inserted via a cannula into the vicinity of the tumour to be irradiated. The dosimeter should remain in the patient's body until radiation therapy has been completed. The basic principle of the fiberoptic dosimeter is to measure the additional attenuation generated in the fiber by irradiation. A lead-glass fiber with 60 weight - % PbO was used as a particular radiationsensitive fiber. This is a step-index fiber with a core diameter of 100 pm and a total diameter of 110 pm. Measurements of the spectral distribution of the induced loss result in a detection sensitivity of smaller than 0.1 Gy for the lead-glass fiber at a local resolution of about 2 cm. This satisfies the demands of radiotherapy.

To prevent a false laser irradiation to an urotherial tissue during the laser stone fragmentation, we applied the fiber-optic pulsed photothermal radiometry (PPTR) to discrimination between urinary stones and urotherial tissues. The experiment was made in vitro with the various wet sample of the urinary stones and the canine urotherial tissues. Three different lasers, ultraviolet argon laser(UV Ar laser), visible argon laser(Vis. Ar laser) and carbon monoxide laser(CO laser), were used for excitation light sources of the PF'TR method and compared to obtain clear discrimination between the stones and the tissue. The UV Ar laser gave the best result among them. The wet canine urotherial tissue was clearly differential from the urinary stones by the measurement of the e-folding decay time of the PPTR waveform.

This paper will evaluate the potential applications of SERS for bio- and biomedical sensing. The emphasis willbe on technologies which will allow the development ofcost effective SERS instrumentation. Potential techniques which can be adapted to fiber optic based sensing will also be discussed.

SERS of catecholamines and histamines is discussed. The SERS of histamines is partially assigned. The use of cellulose acetate electrodes for SERS in matrices with a high protein burden is described.

The Resonance Raman spectra of hemoglobin (Hb) molecules are exclusively due to scattering of the heme group, and the spectrum of a partially oxygenated Hb sample can be employed as a measure of oxygen partial pressure. A optical fiber oxygen sensor based on immobilized Hb is proposed by taking advantage of the Resonance Raman spectra of oxyHb and deoxyHb.

Surface-enhanced Raman spectroscopy has been used to detect low levels of several chemical compounds, including the drugs of abuse -cocaine hydrochloride and methamphetamme hydrochloride. Raman spectra of these substances have also been taken over optical fibers using red-wavelength excitation. These measurements demonstrate the feasibility of the remote determination of various target chemicals using diode laser excitation and diode array detection.

The characteristics of an optical fiber sensor for the entero-gastric reflux are described. Two different probes are developed for "in vivo" measurements making use of PCS fibers (200 um core diameter) and of a fiber bundle respectively. The performance of the sensor and of the two probes are discussed and experimental "in vivo" results are reported.

Fiber optics, thanks to its many advantages finds new areas of ap plication in medicine. This paper describes a fiber optic pressure sensor system. A short sensor theory, a building of a sensor probe and a callibration during measure methode are given.

Ultrasonic intravascular imaging is a rapidly developing technology that permits unique visualization of the inner architecture of peripheral and coronary vessels. A number of groups have published limited trials using these devices directed at assessing their safety and ability to accurately represent endovascular detail. The challenge that lies ahead is to prove that this technology is useful clinically for the diagnosis and treatment of vascular disease. The potential clinical utilities that appear realistic include; (i) quantitating the degree of vascular stenosis, (ii) guiding interventional therapies, and (iii) tissue characterization of atheromatous plaques. Although preliminary results are encouraging in each of these categories, additional work is needed to determine what clinical impact this imaging modality will have in vascular disease.

We have previously described a method for the 3-D visualisation of arterial structures using the voxel space approach to three-dimensional solid modelling. The system we use for intra-arterial imaging, in vitro and in vivo, is based on ultrasonic data, acquired with a purpose-built, catheter-mounted ultrasound probe. In this paper, we describe the methods employed for the reconstruction of 3-D models from these 2-D ultrasonic data and present preliminary work on tissue differentiation, using arterial models and colour-coding of the image.

In this paper, we discuss some of the problems associated with attempting to image blood vessels using ultrasound from an intravascular approach. These include device miniaturisation, ultrasonic problems, difficulties with positioning and orientation of the device, and problems associated specifically with imaging catheters incorporating mechanically rotating parts. Some of the possible solutions are suggested, in terms of modification of transducer design, which may ultimately allow us to realise the goal of directing intraluminal treatment devices by means of intravascular, ultrasonic imaging.

The manifestation of atherosclerotic lesions in arteries can vary from asymptomatic thickening in the vessel wall to complete occlusion. Experimental studies on non-human primates and on human subjects indicate that atherosclerotic lesions may progress without a reduction in luminal diameter because of dilatation of the arterial wall . Although angiography has been considered the "gold standard" for visualization of the arterial tree ar1 detection of luminal narrowing, it does not demonstrate arterial wall thickening or morphology. Moreover, the measurement of luminal diameter of the sane lesion can vary considerably depending on the plane of projection of the x-ray beam. This is attributed to the eccentric nature of the residual lumen in an atherosclerotic vessel . Extraluminal B-mode real time imaging has the feasibility of demonstrating arterial lumen and arterial wall thickness. However, it is still in some instances limited by inadequate resolution and image quality. Intraluminal ultrasound using a phased array or rotating transducer gives better definition of the vessel wall and luminal diameter as it is not limited by the tissue interposed between the vessel and the probe in transcutaneous devices. This paper demonstrates further experience with intravascular ultrasound as a diagnostic tool using B-mode real time imaging.

The application of direct laser energy for the ablation of atherosclerotic plaque has been investigated extensively. It has been recognized that the need for an onboard guidance capability which can direct the laser energy is essential for controlled plaque removal. Intravascular ultrasound represents one approach for identifying diseased tissue and directing laser therapy. The design of a catheter with combined laser and ultrasound capabilities is discussed. The design considers the optical and acoustical requirements. In addition, vascular anatomical constraints and their impact on the mechanical aspects of the device configuration are considered. The optical considerations dictate safe and predictable high energy laser transmission. The acoustic requirements consider material properties and ultrasonic beam resolution. The vascular anatomy imposes constraints on maximum catheter size and it requires a means for conventional delivery of the device to the targeted lesion.

The combination of holographic metrology with endoscopic imaging allows the development of a new class of minute instruments for high-resolving, noncontactive, non-destructive quantitative diagnostics within body cavities. This includes the analysis of structure, form, deformation and vibration of the object under study. There are two possibilities of holographic endoscopic recording: at the distal end within the instrument or with an external holographic camera. In both cases optical fibers are essential for easy handling and flexibility of the holographic endoscopic system. Avantages and drawbacks of optical fiber use are discussed and examples of medical applications are presented.

Seven illumination wavelengths from 270 to 364 nm were investigated for their ability to produce differences in the fluorescence spectra between normal aorta and atheromatous plaque. Differences in the spectra were evaluated using the Hotelling trace and ROC methods. The results indicate that large spectral differences and, therefore, good classification can be obtained with illumination in the range from about 304 to 334 nm and that the performance drops off rapidly on either end of the illumination range.

Of the various holographic measuring methods, holographic interferometry has found the broadest application in biological and medical research. It allows for non-destructive evaluation and for high resolution deformation analysis. By combining holographic interferometry with endoscopic imaging it is possible to obtain holographic imaging inside natural cavities of the body , thus making possible intracavitary measurements of size, shape or deformation of the objects under study. Some applications of holographic interferometry with endoscopic imaging are reviewed in this paper.

Fluorescence bronchoscopy with a ratio fluorometer probe was used to examine patients with known or suspected bronchogenic carcinoma to determine if early lung cancer can be detected with low dose Photofrin II without skin photosensitivity. Seventeen patients were examined 24 hours after injection of 0.25 mg/kg Photofrin II. Using a red-green (R/G) ratio of greater than 1.5 times the mean value of normal areas as being potentially significant, both carcinoma in situ and invasive cancers were accurately localized (sensitivity 100%, specificity 61%). The majority of the false positive fluorescence (80%) came from the lesions with dysplasia. The elevated R/G ratios from the cancerous and pre-cancerous lesions were found to be due to a significantly lower green autofluorescence. No skin photosensitivity was observed on all seventeen patients. Ratio fluorometry was also carried out in thirty-one patients with known or suspected lung cancer without Photofrin II. A similar diagnostic accuracy was found (sensitivity 90%, specificity 86%). Our results suggest that early lung cancer may be detectable by ratio fluorometry by exploiting autofluorescence differences between tumor and normal tissues.

Hyperbiirubinemia is a serious condition affecting many neonates, andthere is a clinical need to monitor the bilirubin levels in susceptible infants. Transcutaneous bilirubinometry by means of an optical patch taped onto the skin would offer an inexpensive, non-invasive method to measure the bilirubin levels in infants. Such a system should give reliable bilirubin readings invariant with the melanin pigmentation, water content, and condition of the skin. We have determined the optical properties of neonatal skin. We are using these optical properties to create scaled phantom models of the skin, and to conduct Monte Carlo computer simulations of light propagation in skin. These models are being used to study how reflectance spectroscopy is affected by the spatial distribution of absorbing chromophores in the skin, and by the wavelength dependence of light collection.

An angioscopic imaging system involves several interfaces among its optical and mechanical components. For best results, the system should be optimized at least to the level of its weakest link. As with any multi-component system, the process of optimizing an angioscope system begins with careful analysis of the functional properties of each component followed by a design study to determine how the components work together. The component technology has evolved to provide sufficient image quality so that the physician-user can use the information for diagnostic applications.

We have developed a new, steerable microangioscope for performing percutaneous coronary angioscopy. The angioscopic catheter is made of polyethylene, contains a distal balloon for occlusion of blood flow during imaging, fits through an 8 Fr percutaneous coronary angioplasty (PTCA) guiding catheter and is steerable by means of a guidewire. Initial feasibility was demonstrated in animal studies involving both peripheral and coronary arteries. Angioscopic findings in normal vessels included normal endothelial surface, collateral blood flow, and side branches. Angioscopy was also performed after balloon denudation of the arteries, laser- assisted balloon angioplasty, and stent implantation. In early human clinical trials we have performed percutaneous angioscopy in six patients undergoing percutaneous coronary angioplasty without complications. Findings in these patients include atherosclerotic plaque, thrombus, and dissection. This new device has great potential for use in the research, diagnosis, and treatment of coronary atherosclerosis.

In this paper, we show how 3-D arterial visualisations may be combined with a 3-D representation of blood flow. We have developed techniques for the estimation and representation of the entire 3-D flow field for the section of artery under investigation. The flow fields are calculated from numerical solutions of the Navier-Stokes equations by a flow solver using a finite difference approach. In order to achieve this, both the profile of the inlet velocity waveform and the shape of the external grid structure of the flow field, derived from the 3-D solid model, are required. Clinically useful 3-D flow information is presented effectively by using a combination of 2-D cross-sectional displays.

A multipurpose digital imaging device has been developed for applications in quantitative densitometry, light scatter detection and fluorescence emission measurement. The Scanning Laser Imaging (SLI) device consists of a three-dimensional laser beam controller, a fiber optic faceplate coupler, a specially designed photodetector assembly and a support computer that has interactive control over the beam positioner. Image information is collected as measurement of either total forward light loss, forward direction scattering or fluorescent emission, depending on the nature of the biological target and the configuration of the detection assembly. Signal output from the bulk photodetector is digitized and assigned to the corresponding pixel location illuminated by the laser spot. The target and detector assembly are stationary while the laser spot is scanned in a programmed pattern. Areas up to 16 cm2 are scanned at a rate of 5.1 x iO pixels/s with 12 bits gray level detection range per pixel. Typically, 1024 x 1024 pixels are captured in less than 30 seconds and stored for display, processing or archiving. Spatial resolution for image reconstruction is a function of laser spot size and has been demonstrated to 3 pm. Rescan and arbitrary laser spot positioning is accomplished to within Biological, biophysical, clinical instrumentation and optical and computer engineering applications of this technology are broad. SLI methods have been developed for quantitative densitometric analysis of electrophoretic gels, thin-layer chromatography plates and autoradiographic materials generally used in molecular biology research. These applications are not well suited for conventional scanning densitometry, particularly when translucent materials such as nylon or nitrocellulose transfer membranes are used because of loss in resolution due to scattering. The SLI spatial resolution is not affected significantly by such scatter. Other quantitative analysis such as measurement of immunofluorescent and immunochemical staining of cells from blood samples and tissue sections can be performed with the SLI device. These applications are poorly suited for traditional flow cytometry, which requires dispersal of individual cells from the tissue. In addition to imaging, the SLI device is capable of detecting and analyzing the occurrence of very rare events. It is routinely capable of scanning a large transparent or translucent target, detecting submicron particles and recording the position of the particles to within approximately 1 pm. The system will detect and locate a single submicron particle placed anywhere on a 800 mm2 surface, a task analogous to locating a standard typewritten character placed on a football field, within 30 seconds.

In 198k we developed a method of hyperthermia using Nd:YAG laser (laser thermia) a system for transmitting continuous low power energy (2 W) through an artificial sapphire interstitial probe for local hyperthermia (43-0.5°C). Our experimental and clinical evidence indicated that this method is safe and effective. The process of tumor destruction induced by laser thermia is, however, poorly understood. We performed in vivo histopathological studies and obtained the following results; 1) At the tissue level, the initial change after laser thermia was the damage of tumor feeding vessels. 2) At the cell level, immediately after laser thermia the mitochondria in the intracellular organella were completely destroyed.

The computer controlled Laserthermia system by the method of using double channel endoscope with the contact frosted probe and a thermocouple was reported previously.25 In this paper, the single channel method with the new single laser delivery system was studied experimentally. Especially hyperthermal effect by the newly developed Hybrid Laserthermia feedback probe(Hybrid probe) was discussed comparatively with the effects by the interstitial contact probe. The Hybrid probe could be possible to treat clinically more accurate Laserthermia in the near future.

We investigated the use of a new Nd:YAG laser irradiation method, 'balloon laserthermia' I involving use of a balloon filled with a light diffusing substance attached to the end of a quartz fiber. This balloon laserthermia technique, using a 3cm diameter balloon containing 0.25% Intralipid solution, was tested on a Meth-A sarcoma in Balb-C mice. A 20 minute irradiation at 20 watts resulted in the following necrosis rates: control group -4%; 40.0-40.5°C. 35%; 42.5-62%; 50.0 -50.5°C. - 97%. When the balloon size was reduced from 3 to 2cm, the optimum values for hypertherinia were a 0.5% Intralipid solution density and a laser power output of 10 watts. As previous use of balloon laserthermia has generally involved use of quartz fibers with a standard 8° angle of light emission, these experiments included trials of a fiber with a 40°light emission angle, along with various combinations of solution densities and laser output conditions. When used with 0.25% Intralipid I the wide-angle fiber provided a power density distribution around the balloon equivalent to that of the standard fiber, but with only half the laser output for hyperthermia, about 10 watts.

A new designed interstitial probe (hybrid probe) was used to treat small hepatocellular carcinoma(HCC) with laserthermia. Before the human study, testing in normal rabbit liver was done to measure the thermal map. And then laserthermia was studied in human small HCC. The set condition was 43-45° C in thermocouple and the duration of laserthermia was 20 minutes. From the follow-up computed tomography and liver biopsies, laserthermia had tumorcidal effect. It is concluded that laserthermia may be helpful to the patients with small HCC.

A new laserthermia system using Nd:YAG laser with a hybrid laserthermia probe was developed to overcome a certaine disadvantage of conventional laserthermia system with a frosted tipped cantact probe. Experimental and clinical studies ravealed that laserthermia system using a hybrid laserthermia probe was effective, easy, and safe to treat deep seated brain tumors.

Interstitial laser hypefthezmia is a tecbnique for the treatment of malignant tumors that involves heating a tumor volume by directing infrared laser light, usually from an Nd: YZG laser, into the volume through interstitially iirlanted optical fibers . We have developed a multi-source, multi-sensor corruter controlled laser hyperthermia system similar to that first described by Daikuzono et al .' In this system, irrlanted inicrothermocouple sensors provide internal terrerature feedback to an algorithm that dynamically deteimines how much light should be directed into the various optical fiber sources, in order to maintain a spatially and tenporally unifoirn teriperature distribution in a tumor volume. This algorithm allows for the tissue thermal response to light to change over time (nonlinear system) , for exarrle, as tissue terterature increases or as tissue damage is incurred. The algorithm eiiploys an original nonlinear system control method that involves a periodic and indirect determination of how each microthermocouple responds to a unit irrulse of light directed down each fiber. Initial testing of the system in a ground beef phantom is described. By accommodating a nonlinear system, our irrlementation of laser hyperthermia should allow for optimal teirerature control.

First results of diode laser spectroscopy methods applications for diagnosing the gas content of expired air are presented. Carbon monoxide (CO) contents of expirations of a sportsman and a smoker were subjected to analysis by using a computerized diode laser system. In the first case there was detected a considerable growth of CO concentration after an intensive exercise. In the second one there were revealed and measured three time constants - characteristics of CO removal from the organism. Promising trends of development and applications of diode laser spectroscopy in medicine are at issue.

Surface-enhanced Raman (SER) spectroscopy has been used to probe the adsorption, surface interactions, and orientations of peptides on metal surfaces. Amino acids in homodipeptides give SER spectra with unique features that can be used to characterize the surface interactions of specific functional groups in more complicated peptides. In heterodipeptides, there is a hierarchy of functional group-surface interactions that prescribe their orientation and conformation on metal surfaces. By establishing this hierarchy, it is now possible to predict the interactions that occur between larger peptides and surfaces. Furthermore, the observed trends suggest that it should be possible to control these interactions by varying the solution pH, the charge on the surface, and other parameters of the measurement in order to adsorb species selectively from mixtures of peptides in solution. Potential biomedical applications of this technique will be described.