Time-resolved diffusing wave spectroscopy applied to dynamic heterogeneity imaging.

We report what is to our knowledge the first observation of a time-resolved diffusing wave spectroscopy (DWS) signal recorded by transillumination through a thick turbid medium: the DWS signal is measured for a fixed photon transit time, which opens the possibility of improving the spatial resolution. This technique could find biomedical applications, especially in mammography.

Time-resolved diffusing wave spectroscopy beyond 300 transport mean free paths.

We presented theoretical and experimental demonstrations of the possibilities of performing time-resolved diffusing wave spectroscopy: We successfully registered field fluctuations for selected photon path lengths that can surpass 300 transport mean free paths. Such performance opens new possibilities for biomedical optics applications.

Time-resolved measurements from speckle interferometry.

We present time-resolved measurements by speckle interferometry of the light scattered by a liquid medium. Measurements were performed by use of reflectance geometry and are compared with results obtained in the same conditions with a femtosecond laser and a streak camera. The setup was also tested in vivo on the forearm of a human volunteer to demonstrate the potential utility of such a setup for biomedical applications.

Real-space Green's function calculation for the solution of the diffusion equation in stratified turbid media.

We have derived the space-time Green's function for the diffusion equation in layered turbid media, starting from the case of a planar interface between two random scattering media. This new approach for working directly in real space permits highly efficient numerical processing, which is a decisive criterion for the feasibility of the inverse problem in biomedical optics. The results obtained by this method in the case of a two-layered medium are compared with Monte Carlo simulations.

The isometric force that induces maximal surface muscle deoxygenation.

To determine the external force that induces maximal deoxygenation of brachioradialis muscle 32 trained male subjects maintained isometric contractions using the elbow flexor muscles up to the limit time (isotonic part of the isometric contraction, IIC) and beyond that time for 120 s (anisotonic part of the isometric contraction). During IIC each subject maintained relative forces of either 25% and 70% maximal voluntary contraction (MVC), 50% and 100% MVC, or 40% and 60% MVC. Muscle oxygenation was assessed using a near infrared spectroscope, and expressed as a percentage of the reference value (deltaO2rest) which was the difference between the minimal oxygenation obtained after 6 min of ischaemia at rest and the maximal reoxygenation following the release of the tourniquet. During IIC at 25% MVC, muscle oxygenation decreased to 17 (SEM 3)% deltaO2rest, then it levelled off [25 (SEM 1)% deltaO2rest]. After the point at which target force could not be maintained, reoxygenation was very weak. During IIC at 40%, 50%, 60%, and 70% MVC, the lowest muscle oxygenation values were obtained after 15-20 s of contraction and corresponded to -18 (SEM 6), -59 (SEM 12) -31 (SEM 6), and -29 (SEM 6)% deltaO2rest, respectively. For the contraction at 100% MVC, the lowest oxygenation [-19 (SEM 9)% deltaO2rest] was obtained while force was decreasing (69% MVC). During the anisotonic part of the isometric contractions, the greatest reoxygenation rate was obtained after 50% MVC IIC (P < 0.001). Our results showed that during isometric elbow flexions between 25% and 100% MVC, there was no linear relationship between external force and muscle oxygenation, and that the maximal deoxygenation of the brachioradialis muscle was obtained at 50% MVC.

The role of laser-induced autofluorescence spectroscopy in bladder tumor detection. Dependence on the excitation wavelength.

We assessed the ability of laser-induced autofluorescence spectroscopy to distinguish neoplastic urothelial bladder lesions from normal or nonspecific inflammatory mucosa. Three different pulsed laser excitation wavelengths were used successively: 308 nm (xenium chloride excimer laser), 337 nm (nitrogen laser) and 480 nm (coumarin dye laser). The excitation light was delivered by a specially devised multifiber catheter connected to a 1-mm core diameter silica monofiber introduced through the working channel of a standard cystoscope with saline irrigation. The captured fluorescence light was focused onto an optical multichannel analyzer detection system. Performance of this device was evaluated in 25 patients after obtaining consent and immediately before transurethral resection of a bladder tumor. Spectroscopic results were compared with histological findings. At 337- and 480-nm excitation wavelengths, the overall fluorescence intensity of bladder tumors was clearly decreased compared to normal urothelial mucosa regardless of tumor stage and grade. At the 308-nm excitation wavelength, the shape of the tumor spectra, including carcinoma in situ, was markedly different from that of normal or nonspecific inflammatory mucosa. No absolute intensity determinations were required in this situation, since a definite diagnosis could be established based on the fluorescence intensity ratio at 360 and 440 nm. This spectroscopic study could be particularly useful in designing a simplified autofluorescence imaging device for detection of occult urothelial neoplasms.

Influence of the emission-reception geometry in laser-induced fluorescence spectra from turbid media.

Routine clinical detection of precancerous lesions by laser-inducedautofluorescence was recently demonstrated in several medicalfields. This technique is based on the analysis of complex spectrawith overlapping broad structures. However, in biological tissues, scattering and absorption are wavelength dependent, and the observedfluorescence signals are distorted when the illumination and detectiongeometry varies, making comparison of results from different groupsdifficult. We study this phenomenon experimentally in human tissuein a simple experiment: A fiber is used for the excitation and anidentical fiber is used for reception of the signal; both fibers aremaintained in contact with the tissue. We study the distortion ofthe spectra as a function of the distance between the twofibers. For correction of the spectra we show that it is possibleto use a fast and accurate ab initio Monte Carlo simulationwhen the spectral variations of the optical properties of the mediumare known. The main advantage of this simulation is itsapplicability even for complex boundary conditions or when the sampleconsists of several layers.

Laser induced autofluorescence diagnosis of bladder tumors: dependence on the excitation wavelength.

PURPOSE: We assessed the ability of laser induced autofluorescence spectroscopy to distinguish neoplastic urothelial bladder lesions from normal or nonspecific inflammatory mucosa. MATERIALS AND METHODS: Three different pulsed laser excitation wavelengths were used successively: 308 nm. (xenium chloride excimer laser), 337 nm. (nitrogen laser) and 480 nm. (coumarin dye laser). The excitation light was delivered by a specially devised multifiber catheter connected to a 1 mm. core diameter silica monofiber introduced through the working channel of a standard cystoscope with saline irrigation. The captured fluorescence light was focused onto an optical multichannel analyzer detection system. Device performance was evaluated in 25 patients after obtaining consent and immediately before transurethral resection of a bladder tumor. Spectroscopic results were compared with histological findings. RESULTS: At 337 and 480 nm. excitation wavelengths the overall fluorescence intensity of bladder tumors was clearly decreased compared to normal urothelial mucosa regardless of tumor stage and grade. At the 308 nm. excitation wavelength the shape of the tumor spectra, including carcinoma in situ, was markedly different from that of normal or nonspecific inflammatory mucosa. No absolute intensity determinations were required in this situation, since a definite diagnosis could be established based on the fluorescence intensity ratio at 360 and 440 nm. CONCLUSIONS: This spectroscopic study could be particularly useful to design a simplified autofluorescence imaging device for detection of occult urothelial neoplasms.

Argon laser induced autofluorescence may distinguish between normal and tumor human urothelial cells: a microspectrofluorimetric study.

PURPOSE: To assess the ability of argon laser-induced autofluorescence spectroscopy (LIAFS) to discriminate normal from tumor human urothelial cells. MATERIALS AND METHODS: Emission spectra of single living cells excited at 488 nm. have been studied with confocal microspectrofluorimeter. RESULTS: Cellular autofluorescence appeared as a broad band with a maximum in the same "green" spectral range, 550 to 560 nm., probably corresponding to oxidized flavoprotein emission. However, the maximum autofluorescence intensity of normal urothelial cells was much higher, 10 times (p<0.0001) that of any of the tumor cell types tested. CONCLUSIONS: These results, suggesting a significantly reduced oxidized flavoprotein concentration in tumor urothelial cells, should prompt us to evaluate argon LIAFS as a potential tool to detect occult urothelial severe dysplasia and carcinoma in situ.

Stimulation in the rat of a nerve fiber bundle by a short UV pulse from an excimer laser.

A bundle of central nervous fibers was excited in the rat with a short pulse (40 ns) of UV light produced by an excimer laser. Evoked responses were recorded in the thalamic ventralis posterior nucleus after stimulation of the medial lemniscus or the cuneate bundle in the spinal cord. The effects of electrical and optical fiber applied UV stimulation were compared in both cases. At threshold, the latency for the UV light stimulation was slightly longer than for electrical stimulation. The excitation threshold was 0.9 J/cm2, very close to the UV photoablation threshold (order of 1 J/cm2). The intermediary events mediating the light excitation are discussed.

Intraoperative coronary artery endarterectomy with excimer laser.

Compared with continuous-wave lasers, excimer lasers exhibit several in vitro advantages: nonthermal ablation process and linear relation between the number of pulses and the depth of the crater. A 308 nm, 20 nsec pulse duration, 1 to 5 repetition rate laser was specifically designed for clinical application. At the time of cardiopulmonary bypass in 10 symptomatic patients, before bypass grafting, a 1 mm diameter core specifically ultraviolet-tipped fiberoptic scope was introduced via the coronary arteriotomy and placed upstream (seven patients) and downstream (three patients) in contact with the stenosis. Laser power was increasingly delivered up to the clearing of the stenosis or occlusion. Quality of angioplasty was controlled by calibration of the neolumen, cardioplegic solution output through the laser-treated segment, and an eighth day or sixth month coronary arteriogram. In the first three patients studied on the eighth day, all laser-treated coronary artery segments showed an early parallel-linked patent neolumen despite competitive bypass graft flow. In the patients studied after 6 months, all recanalized segments were patent except one; in one patient the venous graft was occluded, but the upstream laser angioplasty was patent. The main limitation of the method lies in the fact that laser coronary recanalization is confined to the fiber core diameter. We conclude that (1) excimer laser angioplasty may be safe and efficient during surgical procedure and (2) as catheter flexibility remains the most critical problem, we are now assuming an appropriate tool with a multifiber system that is suitable for intraoperative as well as percutaneous routes.

XeCl excimer laser coronary angioplasty: a convergence of favourable factors.

The results of recent studies on the application of an XeCl laser to coronary angioplasty are presented. Several points are examined: the quality of the cut in human post-mortem artery, the cutting rates and threshold fluences in different media, the risks of carcinogenesis and thrombosis, and the transmission of suitable fluences in optical fibres. Recent human in vivo procedures are reported.

XeCl laser action at medium fluences on biological tissues: fluorescence study and simulation with a chemical solution.

A rat heart, isolated and perfused, was irradiated with a XeCl excimer laser at 308 nm. The evolution of the fluorescence spectrum was measured. For an incident energy E greater than 4 kJ m-2 per pulse the fluorescence changed with time in a complex and spectrally non-uniform way. The proposed interpretation is that the radiation acts on the cellular respiratory chain. Buffered solutions of NADH, cytochrome c and FAD, which play a role in the respiratory chain, were irradiated in order to simulate the in vivo findings. The conclusion of this study is that XeCl radiation introduces a modification in the functioning of the respiratory chain: it accelerates electron transfer, but this quickly leads to an interruption of the respiratory chain.

[Coronary endarterectomy using an excimer laser. Preliminary peroperative results]. / Endartériectomie coronaire par laser à excimères. Résultats peropératoires préliminaires.

From experimental and clinical experience, safe coronary angioplasty cannot be performed with CW lasers. The excimer laser does present a number of advantages in vitro: non-thermal ablation of plaques and a linear relationship between the number of pulses and the depth of the crater, so that tissue ablation is quantitatively predictable. A 308 nm, 20 ns pulse duration, 1 to 5 repetition rate laser was specifically designed for clinical application. During cardiopulmonary bypass prior to bypass grafting in 10 symptomatic patients, a 1 mm diameter core UV-tipped fiberoptic was introduced via the coronary arteriotomy and directed in contact with the coronary stenosis. Laser power was progressively increased until the stenosis or occlusion was recanalized. The quality of this angioplasty was controlled by calibration of he neo-lumen, cardioplegia solution flow through the lased segment, and 8th day coronary angiography. The laser treated coronary segments of the first 4 patients showed clearly parallel-lined patent neo-lumen despite competitive bypass graft flow. The main limitation of the method is that laser coronary recanalization is confined to the fiber core diameter. The authors conclude that: 1) excimer laser angioplasty is a safe and efficient intra-operative procedure; 2) the most critical problem for percutaneous laser angioplasty remains flexibility of the apparatus as the fiber diameter must be large enough to provide an adequate arterial neo-lumen.

[Angioplasty of coronary arteries by laser radiation in 1988]. / L'angioplastie des artères coronaires par rayonnement laser en 1988.

The ability of laser radiation to destroy healthy or pathologic vascular tissue in vitro and in vivo marked the beginning of therapeutic ablation of atheromatous deposits in man. The problems encountered by application of this procedure to treatment of coronary heart disease are very complex, and experience acquired using lasers for peripheral vascular disease is of not much help in this area. It is clear that continuous emission lasers (YAG, Argon, CO2), which produce coagulation necrosis, thrombosis, and vasospasm must be ruled out in favor of impulse type lasers (CO2TEA, YAG Q-S, pumped lasers with dye and exciplex lasers) if the latter can provide a critical thermal relaxation time. Currently, exciplex lasers are a possible method whose potential efficacy and safety gave been demonstrated with certainty in coronary angioplasty. Indeed, although their mechanism of action is poorly understood, they offer the twofold advantage of being able to focus on a volumetrically defined ablation, and to leave the surrounding tissue intact. The clinical application of these tools remains to be developed. Laser angioplasty requires in situ diagnostic methods based on the optical utilization of intrinsic and extrinsic chromophores, the objective of intensive research. Its relative role in comparison to other methods of ablation, and specific indications remain to be defined.

[Contribution of excimer laser to coronary angioplasty]. / Apport des lasers à excimères à l'angioplastie coronaire.

Reports on the problems encountered with thermal laser system in angioplasty have prompted us to test an excimer Xe-Cl laser of 308 nm wavelength and 20 ns impulses on preparations of healthy and atheromatous coronary arteries, the purpose of the study being to quantify the adequate parameters required for angioplasty. We effectively used optic fibres of different diameters--a method which has not yet been reported in medical literature. Our choice of an ultraviolet laser was justified on theoretical grounds: essentially its mode of photo-ablation devoid of thermal effects and proportional to the number of inter- and intramolecular bonds destroyed. The photo-ablation threshold we measured being 1.40 J/cm2, we micrometrically determined the volume of matter removed by various combinations of energy intensities and numbers of impulses, as well as the undesirable effects of such combinations. We found that with an energy surface density of 4.23 J/cm2 the depth of ablation was directly proportional to the number of impulses (between 20 and 100). Under these experimental conditions, the ablation produced by the Xe-Cl laser system was 14 microns per impulse in depth, and of the same diameter as that of the optic fibre used. Virtually identical data were obtained in healthy, fibrotic, atheromatous and calcified tissues. Undesirable effects, i.e. coagulation necrosis, only appeared with high-intensity energies irrelevant to the study. No lesion of the parietal cells was observed, even in the vicinity of the ablation plane. Finally, the question of oncogenic effects raised with 193 nm laser beams does not seem to apply to the 308 nm wavelength.(ABSTRACT TRUNCATED AT 250 WORDS)