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Biomedical subjects

S Mordon

Publications and source records attributed to S Mordon.

At least 55 records · Page 3Linked to original sources

Selective laser photocoagulation of blood vessels in a hamster skin flap model using a specific ICG formulation.

BACKGROUND AND OBJECTIVE: The present study was undertaken to evaluate the selective laser photocoagulation of blood vessels in a hamster skin flap model using a specific indocyanine green (ICG) formulation. STUDY DESIGN/MATERIALS AND METHODS: Experiments were performed in a hamster skin flap model after injection of ICG in aqueous solution (ICGA), or after injection of a specific formulation of ICG (ICG in emulsion: ICGE). Laser irradiation was achieved 30 minutes after injection with a 300 microns fiber connected to a 805 nm diode laser (power = 0.8W, spot diameter = 1.3 mm and pulse exposure time lasting from 1 to 5 s). Macroscopic observation and acute histology were performed to compare the tissue effects obtained for each ICG formulation and to assess the selectivity of vessel damage. RESULTS: The ICGE clearance process was slowed down as compared to the ICGA process. After 30 minutes, the concentration of ICG in blood is higher (2.27 +/- 0.4, P < 0.003) for ICGE compared to ICGA. With ICGA, vessel coagulation required a minimum fluence of 240 J/cm2, which led to very significant skin damage. Conversely with ICGE, vessel coagulation required a fluence of 120 J/cm2. With such a fluence, no laser effect could be detected on the skin. Histological examination confirmed blood vessels coagulation in depth, whereas epidermis and dermis remained intact. CONCLUSION: The major restrictions of ICG in aqueous solution, which are the very-short half-life of ICG in blood and consequently the lack of selectivity in blood vessels after a few minutes, are alleviated when ICG is used in emulsion. ICG in emulsion increases the circulating half-life of ICG and moreover confines ICG in the vascular compartment. Thanks to this specific property, it is possible to obtain a selective vascular damage 30 minutes after injection.

Animals↗

[Laser-tissue interactions in urology].

The laser-tissue interaction is a complex phenomenon which is usually classified into 4 distinct mechanisms: electro-mechanical action, photoablative action, thermal action and photochemical action. Fragmentation of calculi by means of a pulsed dye laser is a good example of the electro-mechanical action. The thermal action can induce coagulation and/or volatilisation of tissues. Treatments of bladder tumors, urethral strictures and more recently benign prostatic hypertrophy are based on the laser terminal action.

Hot Temperature↗

Fluorescence measurement of 805 nm laser-induced release of 5,6-CF from DSPC liposomes for real-time monitoring of temperature: an in vivo study in rat liver using indocyanine green potentiation.

BACKGROUND AND OBJECTIVE: This in vivo study examines the validity of using fluorescence measurements of laser-induced release of temperature-sensitive, liposome-encapsulated dye for real-time monitoring of temperature and for prediction of tissue thermal damage. STUDY DESIGN/MATERIALS AND METHODS: An in vivo study is performed in rat liver after i.v. injection of liposomes loaded with a fluorescent dye and i.v. injection of indocyanine green (ICG) for diode laser potentiation. Temperature-sensitive liposomes (DSPC: Di-Stearoyl-Phosphatidyl-Choline) are loaded with 5,6-carboxyfluorescein (5,6-CF). These liposomes (1.5 ml solution) and ICG (1.5 ml solution-5mg/kg) are injected in adult male wistar rats. Two hours later, the liver is exposed and irradiated with a 0.8 W diode laser using pulses lasting from 1-6s (fluence ranging from 16-98 J/cm2). Simultaneously, the fluorescence emission is analysed with an ultrahigh sensitivity intensified camera. RESULTS: The fluorescence intensity I(F) increases linearly from 18 J/cm2 up to 75 J/cm2. These fluences correspond to surface temperatures between 42 degrees C and 65 degrees C. The measurements appear to be highly reproducible. In this temperature range, the accuracy is +/- 3 degrees C. The maximum intensity is observed immediately after the laser is switched off. A decrease of the fluorescence intensity (27% in 20 minutes) is observed due to the 5,6-CF clearance. However, the ratio I(F)/I(BCK) (I(BCK): background fluorescence intensity) remains almost stable over this period of time and the determination of the temperature is still possible with good accuracy even 20 minutes after laser irradiation. CONCLUSION: Real-time temperature monitoring by using fluorescence measurement of laser-induced release of liposome-encapsulated dye is clearly demonstrated. This procedure could conceivably prove useful for controlling the thermal coagulation of biological tissues.

Animals↗

Fluorescent characteristics and pharmacokinetic profiles of the fluorescent probe BCECF in various tissues: the role of blood content.

The purpose of this study was to investigate the in vitro and in vivo spectral characteristics of the fluorescent pH-sensitive probe bis-carboxyethylcarboxyfluorescein (BCECF) in different tissues and its fluorescence kinetics profiles. The in vivo study was performed on anesthetized adult Wistar rats. After intravenous administration (4.8 mg/kg), fluorescence spectra were recorded on the following tissues: skin, an isolated blood vessel and liver. Measurements performed in vitro on blood samples show modifications of the BCECF emission spectrum with a blue-shift (10 nm) and a low fluorescence emission. Blood content greatly influences the pH measurement by increasing the I(490 exc., 530 em.)/I(470 exc., 530 em.) Fluorescence ratio value (ratio of the fluorescence intensities at 530 nm following excitation at 470 nm and 490 nm) when the hematocrit is high. A 0.35 ratio difference is observed between a BCECF-buffered solution and blood samples of 44% hematocrit. The emission spectra recorded on the skin are quite similar to the emission spectrum of BCECF in aqueous solution and are consistent with an extravascular localization of the dye a few minutes after injection. On the contrary, spectra recorded on the blood vessel and the liver are more similar than those recorded in vitro on high hematocrit solutions. Kinetic profiles in skin, liver and isolated blood vessels compared to the clearance obtained by blood sampling provide information about tissue perfusion. Then the variation of in vivo spectra in different tissues may be taken into account to measure tissue pH with special regard to the blood content of the illuminated area and the time range in which the measurement is performed.

Animals↗

Laser photocoagulation around the foci of toxoplasma retinochoroiditis: a descriptive statistical analysis of 35 patients with long-term follow-up.

Thirty-five patients with toxoplasma retinochoroiditis, receiving medical treatment and then treated with laser photocoagulation around the foci, were retrospectively evaluated for the risk of recurrence of the retinochoroiditis with a Kaplan-Meier representation. The recurrence rates with 95% symmetric confidence intervals were: at 1 year, 12.7 + or - 13%, at 2 years, 19.8 + or - 15%; at 3 years, 24.0 + or - 16%; at 4 years, 33.3 + or - 19%; at 5,6 and 7 years, 53.5 + or - 21%; at 8 and 9 years 66. 8 + or - 22%. With the data provided by our series, it is not possible to show the efficacy of laser photocoagulation as a prevention of recurrence in toxoplasma retinochoroiditis. Moreover, because of their heterogeneity, the recurrence rates from the literature cannot provide precise data for a comparison. Concerning the laser-induced thermal damage, the potential therapeutic mechanism of the laser procedure is discussed.

Adolescent↗

[Control of photocoagulation intensity by thermo-induced release of a fluorescent marker encapsulated in liposomes: study of an in vivo vascular model].

PURPOSE: To evaluate the feasibility of thermal damage assessment of blood vessels by using laser-induced release of liposome-encapsulated dye. METHODS: A skin flap window model of aluminium was implanted on the loose skin on the back of adults Golden hamsters to expose skin blood vessels in vivo. Thermosensitive liposomes (DSPC) loaded with 5,6-Carboxyfluorescein were injected together with a specific Indocyanine green (ICG) formulation (O/W emulsion) in order to enhance diode laser absorption. Photocoagulations were then performed on the vessels with a diode laser (lambda = 810 nm, P = 0.8W, phi = 1.3 mm, 1 to 6s). Fluorescence measurements were realized with an ultra high sensitivity intensified camera (Hamamatsu Argus 50 imaging system). RESULTS: Two different fluorescence intensity curves corresponding to the variability of absorption of the targets were observed. Variability was related to the amount of ICG. For each curve, 3 zones were identified: (i) for fluences ranging from 60 +/- 20 J/cm2 to 110 +/- 20 J/cm2 a transient intravascular fluorescence was observed only for the loser pulses targeted on the vessels, (ii) for fluences ranging from 110 +/- 20 J/cm2 to 190 +/- 20 J/cm2 a permanent fluorescent spot limited to the vessel was observed for the laser pulses targeted on the vessels; for the laser pulses targeted on the skin a transient low fluorescence circular spot was observed. For this fluence range a selective photocoagulation of a vessel was performed. (iii) for fluences ranging from 190 +/- 20 J/cm2 to 300 +/- 20 J/cm2 persistent intense fluorescence spots were observed on both skin and vessels. This type of fluorescence was related to an overdosage. CONCLUSION: These results are in fair agreement with the data of the literature about liposomes and with the data we obtained in a previous study on a vascular model. This study demonstrates the interest of a laser-induced release of liposome-encapsulated dye for a real-time quantification of thermal damage. Such a method could be useful for laser photocoagulation in ophthalmology for indications such as choroidal neovessels where the production of a precise thermal damage is required.

Animals↗

Laser-induced release of liposome-encapsulated dye to monitor tissue temperature: a preliminary in vivo study.

BACKGROUND AND OBJECTIVE: The objective of this in vivo study was to assess the possible use of temperature-sensitive liposomes as a new approach to monitor the temperature induced by a laser. STUDY DESIGN: An in vivo/ex vivo study was performed in rat liver after i.v. injection of liposomes loaded with a fluorescent dye. MATERIALS AND METHODS: Temperature-sensitive liposomes (DSPC: Di-Stearoyl-Phosphatidyl-Choline) were loaded with carboxyfluorescein. These liposomes (1 ml solution) were injected into adult male Wistar rats. Two hours later, the liver was exposed and irradiated with a 100 W Nd:YAG laser using pulses lasting from 100 to 260 ms. Simultaneously, the surface temperature was recorded with a thermographic camera. The fluorescence emission was measured with a fluorescent imaging system. RESULTS: The results showed that the dye was released in response to laser energy. The amount of the drug release increased linearly with increasing temperature in the range 42-60 degrees C. Moreover, the release occurred in a short period of time upon brief exposure to its phase transition temperature. CONCLUSION: The feasibility of temperature monitoring by using laser-induced release of liposome-encapsulated dye was demonstrated. This procedure could conceivably prove useful for controlling the thermal coagulation of biological tissues such as blood vessels.

Animals↗

Fluorescence spectroscopy of pH in vivo using a dual-emission fluorophore (C-SNAFL-1).

The aim of this study was to evaluate a dual-emission fluorophore (C-SNAFL-1: 5'(and 6')-carboxyseminaphthofluorescein) for in vivo pH monitoring, using one excitation wavelength and two emissions. P388-tumour-bearing CDF mice were injected intravenously with C-SNAFL-1. Glucose was administered simultaneously to lower the tumour pH. Under our experimental conditions, tissue autofluorescence was found to be negligible. Two emission peaks were observed. The wavelength of the first one was pH insensitive (545 nm). The second one was pH sensitive: a shift of the emission peak as a function of pH was observed from 587 nm for pH 7.25 to 605 nm for pH 6.3. A calibration curve linking emission intensity ratios (I545/I635) to in vivo pH is provided. Results clearly indicate differences between tumorous (ratio 0.55 +/- 0.08, pH 6.3 +/- 0.1) and normal (ratio 1.39 +/- 0.04, pH 7.25 +/- 0.1) tissues. The concept of pH fluorescence spectroscopy in vivo using C-SNAFL-1 provides quantified data and accurate measurements of tissue pH.

Animals↗

In vivo pH measurement and imaging of tumor tissue using a pH-sensitive fluorescent probe (5,6-carboxyfluorescein): instrumental and experimental studies.

This study evaluated the effectiveness of dual-wavelength ratio fluorescence imaging using a pH-dependent indicator (5,6-carboxyfluorescein, 5,6-CF) for in vivo pH mapping of tissue. A prototype version of a highly sensitive fluorescence imaging device consisting of a modified xenon lamp, an image-intensified camera and a digital image-processing system has been developed. 5,6-Carboxyfluorescein was used because its fluorescence emission increases as a function of pH in the physiological (6.0-7.4) pH range. The ratio of fluorescence intensities obtained with the imaging system has been calibrated using aqueous 5,6-CF standards at various pH values. Because the pH of interstitial fluid of malignant tumors tends to be lower than that of normal tissue and can be depressed by glucose administration, experiments were performed on 10 CDF mice bearing lymphoid leukemia P388 grafted subcutaneously. The range of linearity of the calibration curve was obtained between 5.3 and 6.7 with a measured pKa value of 5.93. Consequently the maximum sensitivity was observed in this range. The calculated pH from ratio images was 6.21 +/- 0.12 in tumorous tissue. This value was equivalent to those obtained at the same time using microelectrodes (6.2 +/- 0.3). These experiments showed that a dose of 5 mg/kg 5,6-CF and an excitation power density of 2.5 mW/cm2 are sufficient to give a fluorescent pH image of tumors. The limitation of 5,6-CF for the in vivo mapping of tissue results from its low pKa and consequent range of sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Control of intensity of light coagulation by thermo-induced release of a fluorescent marker encapsulated in liposomes. In vivo/ex vivo preliminary study].

PURPOSE: The aim of this in-vivo/ex vivo study was to assess the possible use of temperature sensitive liposomes in an established model such as the liver as a new approach to monitor the temperature induced by a laser. METHOD: Temperature sensitive liposomes (DSPC: DiStearoylPhophatidyl-Choline: critical temperature: 55 degrees C) loaded with carboxy-fluoresceine were prepared by the Bancham procedure. These liposomes (1 ml solution) were injected to adult male wistar rats. Two hours later, the liver was exposed and irradiated with a 100 W Nd: YAG laser (single pulse mode, pulses ranging from 100 to 260 ms, spot diameter: 4 mm). Simultaneously, the surface temperature was recorded with a infrared thermographic camera (Aga). The fluorescence emission was then measured with a fluorescent imaging system (Hamamatsu). RESULTS: The dye was released in response to laser energy. The amount of the drug release increased linearly with increasing temperature in the range 42 to 60 degrees C. The estimated latency of release seems more related to the heating pattern (i.e. to laser parameters) than to the liposomes. CONCLUSION: This preliminary study assesses the possible use of laser-induced release of liposome-encapsulated dye to monitor tissue temperature and then thermal damage.

Animals↗

Rationale for automatic scanners in laser treatment of port wine stains.

Laser therapy of port wine stains (PWS) is well established. However, the application of lasers to PWS treatment over the last decade has resulted in the use of many laser systems. The goal of this study is to describe the different laser parameters, treatment techniques, and delivery systems. Two methods, coagulation and microvaporization, are used to destroy the abnormal blood vessels. The coagulation method results in excellent treatment, but it requires careful control of laser parameters during the treatment process. Scanning devices can be utilized for this purpose. The microvaporization method, obtained with a pulsed dye laser, is restricted to PWS composed of small vessels since it is difficult to obtain a pulse longer than 450 microseconds. In addition, numerous retreatments are needed with the pulsed dye method. The initial assessment of the patient should contribute to an improvement in the choice of laser parameters and the outcome of treatment.

Adult↗

Relation between skin surface temperature and minimal blanching during argon, Nd-YAG 532, and CW dye 585 laser therapy of port-wine stains.

Laser photocoagulation has proven to be valuable in the treatment of port-wine stains. In this application, the minimal blanching technique is used as an indicator of suitable dosage since it has been demonstrated that the immediate appearance a white mark is required to achieve permanent blanching a few months later. The objective of the investigations undertaken in this study was to correlate the temperature attained at the surface of port-wine stains with immediate blanching, upon irradiation with different laser fluences. A comparative study was performed using an argon laser (all lines), a 532 nm Nd:YAG and a 585 nm argon pumped dye laser. Surface temperature was studied using an infrared camera. Temperature was measured on 10 different port-wine stains using different fluences. Whitening threshold fluence was related to surface temperature. It appeared that whitening threshold fluence corresponded to a surface temperature of 53 degrees C (+/- 3 degrees C). The whitening threshold fluence was dependent on port-wine stains and wavelength. However, whitening threshold fluence remained lower for 532 nm and 585 nm and it correlated to the absorption curve of hemoglobin.

Hemangioma↗

Characterization of tumorous and normal tissue using a pH-sensitive fluorescence indicator (5,6-carboxyfluorescein) in vivo.

The pH of the interstitial fluid of malignant tumours tends to be lower than that of normal tissue and is depressed by glucose administration. This study aimed to evaluate the effectiveness of dual-wavelength fluorometry using a pH-dependent indicator (5,6-carboxyfluorescein: 5,6-CF) for the detection of tumour areas in vivo. 5,6-CF has two main characteristics: it has two wavelengths of maximum absorbance (465 and 490 nm) and its fluorescence emission (maximum, 515 nm) increases as a function of pH in the physiological pH range of 6-7.4. The experimental study was performed on 28 CDF mice bearing lymphoid leukaemia P388 grafted subcutaneously. The tissue pH values were evaluated from the ratio of the fluorescence intensities (I490/I465) on the basis of a calibration curve linking pH measurements performed within the tissue using a microelectrode and values of the fluorescence intensity ratio. The fluorescence intensity reached its maximum value 60 min after 5,6-CF and glucose administration, followed by a plateau (90 min) when the ratios remained constant at 1.79 +/- 0.05 for normal tissue and 1.35 +/- 0.04 for tumour tissue (p less than 0.005). These results were correlated with the pH measurements in accordance with the calibration curve. This study validates the relevance of dual-wavelength fluorometry using a pH-dependent indicator to characterize in vivo normal and tumour tissues after glucose administration.

Animals↗

[Physical basis of therapeutic uses of lasers].

Therapeutic applications of lasers usually require different mechanisms of laser tissue interaction: the thermal interaction mechanism where light energy is converted into heat, the photochemical interaction mechanism where light induces chemical reactions, the mechanical interaction mechanism where light produces shock wave and the photoablative interaction mechanism where light energy produces desorption of tissue. The interaction mechanism depends on the choice of the laser parameters.

Humans↗

[Future of medical lasers].

Whatever the medical field of application of lasers, their future is linked to research and to the realization of systems of automatization which will allow the development of "smart lasers". It will be linked to the improvement of imaging techniques and of medical computers, as well as to the development of new feedback systems; the wavelength and the laser beam dosimetry could then be automatically chosen depending on the aimed tissue and on the biophysical effect desired on the target (coagulation, vaporization, cutting, hyperthermia, photo-ablation). Practically, the future of lasers also depends on the elaboration of new peripheric systems and a better conception of new laser equipment. At last, clinical evaluation of such new surgical technologies with well adapted procedures, formation and information through specific teaching courses and seminars will help to the development of all new laser-technologies.

Education, Medical, Graduate↗