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Biomedical subjects

E D Jansen

Publications and source records attributed to E D Jansen.

13 recordsLinked to original sources

The effect of free-electron laser pulse structure on mid-infrared soft-tissue ablation: biological effects.

Previous studies have shown that changing the pulse structure of the free electron laser (FEL) from 1 to 200 ps and thus reducing the peak irradiance of the micropulse by 200 times had little or no effect on both the ablation threshold radiant exposure and the ablated crater depth for a defined radiant exposure. This study focuses on the ablation mechanism at 6.1 and 6.45 microm with an emphasis on the role of the FEL pulse structure. Three different experiments were performed to gain insight into this mechanism. The first was an analysis of the ablation plume dynamics observed for a 1 ps micropulse compared with a 200 ps micropulse as seen through bright-field analysis. Negligible differences are seen in the size, but not the dynamics of ablation, as a result of this imaging. The second experiment was a histological analysis of corneal and dermal tissue to determine whether there is less thermal damage associated with one micropulse duration versus another. No significant difference was seen in the extent of thermal damage on either canine cornea or mouse dermis for the micropulse durations studied at either wavelength. The final set of experiments involved the use of mass spectrometry to determine whether amide bond breakage could occur in the proteins present in tissue as a result of direct absorptions of mid-infrared light into the amide I and amide II absorption bands. This analysis showed that there was no amide bond breakage due to irradiation at 6.45 microm on protein.

Animals↗

High-dose dexamethasone accentuates nuclear factor-kappa b activation in endotoxin-treated mice.

We examined the effects of dexamethasone treatment on nuclear factor (NF)-kappa B activation and lung inflammation in transgenic reporter mice expressing photinus luciferase under the control of an NF-kappa B-dependent promoter (HLL mice). In vitro studies with bone marrow and peritoneal macrophages derived from these mice showed that treatment with dexamethasone blocked luciferase induction after treatment with Escherichia coli lipopolysaccharide (LPS); however, treatment of mice with intraperitoneal injection of dexamethasone at doses of 0.3 microg/g and 1 microg/g failed to inhibit NF-kappa B-dependent luciferase activity in the lungs. Furthermore, intraperitoneal treatment with 10 microg/g of dexamethasone prior to LPS paradoxically resulted in augmented luciferase activity as compared with that of mice treated with LPS alone. NF-kappa B-dependent luciferase expression in the lungs was detected by bioluminescence imaging and by measurement of luciferase activity in homogenized lung tissue. In these studies, there was an excellent correlation between indirect measurement of luciferase activity by bioluminescence in living mice and direct measurement of luciferase activity in lung tissue. Dexamethasone treatment did not affect LPS-induced neutrophilic influx or the concentration of macrophage inflammatory protein-2 in lung lavage fluid. These findings emphasize the potential error of extrapolating in vitro findings to complex in vivo events such as regulation of inflammation.

Animals↗

In vivo optical imaging of expression of vascular endothelial growth factor following laser incision in skin.

BACKGROUND AND OBJECTIVE: Laser-tissue interaction studies have focused on laser-induced secondary effects on tissue and the postmortem histological analysis of laser wounds. In this study we addressed wound healing and possible impairment of wound healing due to collateral tissue damage by in vivo imaging of gene expression. STUDY DESIGN/MATERIALS AND METHODS: We used a transgenic mouse model containing a VEGF promoter driving a GFP reporter gene to image VEGF expression in vivo. Twenty-two mice received two full thickness incisions in the dorsal skin: one with the Free Electron Laser (lambda = 6.45 microm, 52.9 mJ/mm(2)) and one with a scalpel. Mice were imaged for GFP expression at 3 days, 1, 2, 3, and 4 weeks. Confocal microscopic imaging was performed at 2 weeks. RESULTS: Peak GFP expression was seen at 2-3 weeks and was localized in fibroblasts. FEL lesions showed more total GFP expression than scalpel lesions but this was only statistically significant (P < 0.05) at 2 and 4 weeks. The full-width half-max (FWHM) of the GFP expression was always larger for the FEL lesion compared to the scalpel lesion but was only statistically significant (P < 0.05) at 2 and 3 weeks. At 2 weeks the extent of the GFP expression in the laser lesion was on average 55 microm beyond that seen in the scalpel lesion but correlated with the number of laser passes. CONCLUSIONS: Feasibility of using transgenic mice carrying photoactive reporter genes for studying cellular process of laser-inflicted wound repair in a noninvasive, in vivo manner was shown. GFP expression mediated by the VEGF promoter in fibroblast showed minimal impairment of wound healing due to the laser.

Animals↗

In vivo brain tumor demarcation using optical spectroscopy.

The applicability of optical spectroscopy for intraoperative detection of brain tumors/tumor margins was investigated in a pilot clinical trial consisting of 26 brain tumor patients. The results of this clinical trial suggest that brain tumors and infiltrating tumor margins (ITM) can be effectively separated from normal brain tissues in vivo using combined autofluorescence and diffuse-reflectance spectroscopy. A two-step empirical discrimination algorithm based on autofluorescence and diffuse reflectance at 460 and 625 nm was developed. This algorithm yields a sensitivity and specificity of 100 and 76%, respectively, in differentiating ITM from normal brain tissues. Blood contamination was found to be a major obstacle that attenuates the accuracy of brain tumor demarcation using optical spectroscopy. Overall, this study indicates that optical spectroscopy has the potential to guide brain tumor resection intraoperatively with high sensitivity.

Adult↗

Free electron laser lithotripsy: threshold radiant exposures.

PURPOSE: To determine the threshold radiant exposures (J/cm2) needed for ablation or fragmentation as a function of infrared wavelengths on various urinary calculi and to determine if there is a relation between these thresholds and lithotripsy efficiencies with respect to optical absorption coefficients. MATERIALS AND METHODS: Human calculi composed of uric acid, calcium oxalate monohydrate (COM), cystine, or magnesium ammonium phosphate hexahydrate (MAPH) were used. The calculi were irradiated in air with the free electron laser (FEL) at six wavelengths: 2.12, 2.5, 2.94, 3.13, 5, and 6.45 microm. RESULTS: Threshold radiant exposures increased as optical absorption decreased. At the near-infrared wave-lengths with low optical absorption, the thresholds were >1.5 J/cm2. The thresholds decreased below 0.5 J/cm2 for regions of high absorption for all the calculus types. Thresholds within the high-absorption regions were statistically different from those in the low-absorption regions, with P values much less than 0.05. CONCLUSIONS: Optical absorption coefficients or threshold radiant exposures can be used to predict lithotripsy efficiencies. For low ablation thresholds, smaller radiant exposures were required to achieve breakdown temperatures or to exceed the dynamic tensile strength of the material. Therefore, more energy is available for fragmentation, resulting in higher lithotripsy efficiencies.

Differential Threshold↗

Brain tumor demarcation using optical spectroscopy; an in vitro study.

Optical spectroscopy for brain tumor demarcation was investigated in this study. Fluorescence and diffuse reflectance spectra were measured from normal and tumorous human brain tissues in vitro. A fluorescence peak was consistently observed around 460 nm (+/- 10 nm) emission from both normal and tumorous brain tissues using 337 nm excitation. Intensity of this fluorescence peak (F460) from normal brain tissues was greater than that from primary brain tumorous tissues. In addition, diffuse reflectance (Rd) between 650 and 800 nm from white matter was significantly stronger than that from primary and secondary brain tumors. A good separation between gray matter and brain tumors was found using the ratio of F460 and Rd at 460 nm (Rd460). Two empirical discrimination algorithms based on F460, Rd625, and F460/Rd460 were developed. These algorithms yielded an average sensitivity and specificity of 96% and 93%, respectively.

Algorithms↗

Laser-tissue interaction during transmyocardial laser revascularization.

BACKGROUND: The clinical procedure known as transmyocardial revascularization has recently seen its renaissance. Despite the promising preliminary clinical results, the associated mechanisms are subject to much discussion. This study is an attempt to unravel the basics of the interaction between 800-W CO2 laser radiation and biological tissue. METHODS: Time-resolved flash photography was used to visualize the laser-induced channel formation in water and in vitro porcine myocardium. In addition, laser-induced pressures were measured. Light microscopy and birefringence microscopy were used to assess the histologic characteristics of laser-induced thermal damage. RESULTS: The channel depth increased logarithmically with time (ie, with pulse duration) in water and porcine myocardium. Pressure measurements showed the occurrence of numerous small transients during the laser pulse, which corresponded with channel formation, as well as local and partial channel collapse during the laser pulse. Twenty millimeters of myocardium was perforated in 25 ms. Increasing the pulse duration had a small effect on the maximum transversable thickness, but histologic analysis showed that thermal damage around the crater increased with increasing pulse duration. CONCLUSIONS: Several basic aspects of the interaction of high-power CO2 laser radiation with myocardial tissue and tissue phantoms were studied in vitro. Although the goal of this study was not to unravel the mechanisms responsible for the beneficial effects of transmyocardial revascularization, it provided important information on the process of channel formation and collapse and tissue damage.

Animals↗

Effect of pulse duration on bubble formation and laser-induced pressure waves during holmium laser ablation.

BACKGROUND AND OBJECTIVE: One concern during laser ablation of tissue is the mechanical injury that may be induced in tissue in the vicinity of the ablation site. This injury is primarily due to rapid bubble expansion and collapse or due to laser-induced pressure waves. In this study, the effect of laser pulse duration on the thermodynamics of bubble formation and accompanying acoustic pressure wave generation has been investigated. STUDY DESIGN/MATERIALS AND METHODS: Q-switched holmium:YAG laser pulses (pulse duration 500 ns, pulse energy 14 mJ) and free-running holmium:YAG laser pulses (pulse duration 100-1,100 microseconds, pulse energy 200 mJ) were delivered in water and tissue phantoms via a 200- and 400-microns fiber, respectively. The tissue phantoms consisted of polyacrylamide gels with varying mechanical strengths. Bubble formation was recorded with a fast flash photography setup, while acoustic transients were measured with a needle hydrophone. RESULTS: It was observed that, as the pulse length was increased the bubble shape changed from almost spherical for Q-switched pulses to a more elongated cylinder shape for longer pulse durations. The bubble expansion velocity was larger for shorter pulse durations. Only the Q-switched pulse induced a measurable thermo-elastic expansion wave. All pulses that induced bubble formation generated pressure waves upon collapse of the bubble in gels as well as in water. However, the magnitude of the pressure wave depended strongly on the size and geometry of the induced bubble. CONCLUSION: The magnitude of the collapse pressure wave decreased as laser pulse duration increased. Hence it may be possible to reduce collateral mechanical tissue damage by stretching the holmium laser pulse.

Acoustics↗

Excimer laser induced bubble: dimensions, theory, and implications for laser angioplasty.

BACKGROUND AND OBJECTIVE: Previous studies have demonstrated that during Xenon-Chloride excimer laser ablation of tissue, rapidly expanding and imploding bubbles (diameter < 3 mm), predominantly containing water vapor, are formed. These short lived bubbles (life time < 300 microseconds) induce mechanical damage in adjacent tissue. In the present study, a theoretical analysis of the volume of vaporized water is correlated with measured bubble volumes formed in hemoglobin solution. STUDY DESIGN/MATERIALS AND METHODS: The dimensions of the rapidly expanding and imploding vapor bubble induced by the XeCl excimer laser pulses (308 nm, 115 ns), delivered via a 300, 550, or 950 microns diameter monofiber in 16% w/v hemoglobin solution (at 37 degrees C), were measured. RESULTS: Theoretical analysis and the experimental data correlated well (correlation coefficient r = 0.97). The diameter of excimer laser induced bubbles increased with increasing pulse energy. For a given radiant exposure, the bubble size was decreased by either decreasing the fiber tip area or by decreasing the absorption coefficient of the hemoglobin solution. CONCLUSION: We conclude that, for a wide range of conditions, theory agrees well with experimental data. Thus, during delivery of excimer laser pulses in blood, bubble dimensions can be reduced by flushing with saline or by reduction of the area radiated with each laser pulse, for example, by pulse multiplexing or using a smaller multifiber catheter.

Angioplasty, Laser↗

Temperature dependence of the absorption coefficient of water for midinfrared laser radiation.

The dynamics of the water absorption peak around 1.94 microns was examined. This peak is important for the absorption of holmium and thulium laser radiation. To examine the effect of temperature on the absorption coefficient, the transmission of pulsed Ho:YAG, Ho:YAG, Ho:YSGG, and Tm:YAG laser radiation through water of 22 degrees C, 49 degrees C, and 70 degrees C was measured as a function of the thickness of the water layer. From these data the absorption coefficients were determined at the three wavelengths. We found that at all three wavelengths, the absorption coefficients decreased when increasing the temperature. Second, the absorption spectrum of water was measured from 1,850-2,150 nm with a spectrophotometer. It was found that the absorption peak at 1.94 microns (at 22 degrees C) shifts to shorter wavelengths with increasing temperatures, to 1.92 microns at 70 degrees C. A model was developed to predict the temperature distribution incorporating the dynamic change in absorption coefficient. The temperature distributions are compared to the predictions of a model assuming constant optical properties. It is shown in this study that the dynamics of the absorption coefficient has a significant influence on the expected zone of damage and ablation parameters in the 2-microns wavelength range.

Absorption↗

Mechanism of CW Nd:YAG laser recanalization with modified fiber tips: influence of temperature and axial force on tissue penetration in vitro.

Modified fiber tips are used for laser angioplasty of totally occluded peripheral arteries. It has not been established, however, to what extent the mechanism of action of various laser probes is optical, thermal, or mechanical. We examined transparant contact probes (hemispherical contact probes and ball-shaped fibers) and metal laser probes, coupled to a continuous-wave Nd-YAG laser. By using homogeneous thick porcine fatty tissue samples submerged in blood plasma, tissue penetration was measured in relation to the temperature of the probe and the axial force exerted on the tissue. By using 15 W, 1 s laser pulses, the surface of transparent contact probes had to be first contaminated by carbonized tissue particles to achieve tissue penetration. Penetration increased from 1 to 10 mm per pulse when axial force increased from 20 to 100 g. Metal probes had to be sufficiently insulated from the liquid environment by water vapour entrapped in a denatured protein layer to exceed the threshold temperature of 225 degrees C for tissue penetration. When axial force increased from 20 to 80 g at 10 W continuous exposure, the velocity of tissue penetration increased in the range from 1 to 4 mm/s. Tissue penetration by modified fiber tips is attributed to both remodeling and vaporization of tissue. With transparent contact probes, tissue is heated partly by direct light absorption and partly by a hot probe surface. Axially directed force is necessary to displace lateral non-ablated tissue and to overcome mechanical resistance. We conclude that mechanical dilation due to axial catherization force (Dotter effect) contributes substantially to tissue penetration by transparent contact probes.

Angioplasty, Laser↗

Temperature along the surface of modified fiber tips for Nd:YAG laser angioplasty.

For laser angioplasty probes, the thermal properties of the probes will primarily determine their mechanism of action. We examined the absorption, temperature increase, and probe degradation of transparent contact probes (hemispherical contact probe and ball-shaped fibers) and metal laser probes coupled to a continuous-wave Nd-YAG laser. Temperature was recorded by means of thermocouples and the measurements were corrected for direct light absorption by the thermocouple. During 15 W, 1 s exposure, the peak temperature rise of the hemispherical contact probe in contact with tissue dropped from approximately 1,000 degrees C at the front end to below 45 degrees C (95% drop) at the lateral side. In contrast, during continuous exposure the peak temperature rise of metal laser probes in contact with tissue dropped from 560 degrees C at the front end to near 400 degrees C (30% drop) at the 5.5 mm proximal rear end. During exposure in blood or tissue, the transparent contact probes became contaminated. Their absorption increased from 5 to 33% and the probe deteriorated. Repeated use of metal laser probes in blood resulted in a higher temperature at the rear than at the front end due to backburing of the fiber. Owing to the large temperature drop along the surface of transparent contact probes, the area of thermal destruction is limited to the tissue in front of the probe, whereas along the entire surface of metal laser probes the tissue will be affected. The large difference between these temperature distributions should be respected during clinical application of the transparent contact probe and the metal laser probe.

Absorption↗

In vitro comparison of radiofrequency-heated and laser-heated metal probes for angioplasty.

The effects of a metal probe catheter on tissue using radiofrequency (RF) as its energy source is evaluated. The energy dissipation and the temperature increase of this probe was compared with a laser-heated probe. After 15 seconds, the temperature rise of the RF-heated probe at a maximum power setting was 68 degrees C in water and 106 degrees C in plasma. In contrast, the temperature rise of the Nd:YAG laser-heated probe after 10 seconds, 10 watt (W), was 80 degrees C in water and 595 degrees C in plasma. Calorimetric experiments showed that in a 7 to 30 W range of the power setting for the RF generator, only 3.5 to 4.5 W was dissipated at the RF catheter tip. Using axial forces equivalent to 100 g in fatty tissue, the penetration velocity of the RF-heated probe was 0.015 mm/s, with a temperature rise of the tip of 180 degrees C; whereas the velocity of the laser-heated probe was 3.4 mm/s with a temperature rise of the tip of 300 degrees C. These in vitro results suggest that during clinical application, tissue in contact with the front surface of the RF-heated angioplasty probe will be remodeled, whereas with the laser-heated probe tissue will be vaporized circumferentially. The RF-heated probe's risk of vessel wall perforation is probably small.

Electrocoagulation↗