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A fiberoptic compatible midinfrared laser with CO2 laser-like effect: application to atherosclerosis.

In theory, pulses of laser light in the 2-microns range should ablate tissue in a manner similar to that of the 10.6-microns CO2 laser with the added advantage of efficient transmission through flexible quartz fibers. Using 200-microseconds pulses of 2.15-microns thulium-holmium-chromium:YAG (THC:YAG) laser light, we were able to create 700-microns-diameter holes through calcific atherosclerosis in vitro. In vivo evaluation of thrombogenicity and healing was accomplished by exposing the luminal surface of rabbit aortas to the THC:YAG laser. Serial histologic examinations of laser-treated rabbit aortae revealed a time course of resolution of the lesions which was very similar to that observed with like-sized lesions created with the same amount of continuous wave CO2 energy. No significant differences in thrombogenicity nor healing response were noted. The excellent in vivo response observed is due in part to the pulsed nature of the THC:YAG laser output as well as to the efficient tissue absorption at the 2.15-microns wavelength. We feel that excellent ablative effects with minimal collateral thermal damage can be obtained through fiberoptic delivery systems by taking advantage of laser wavelengths corresponding to the infrared absorption peak of water in the 2-microns region and pulsed delivery of the laser energy.

Animals↗

Ion microscopy, a method for imaging the distribution of trace elements in the lung.

Analytical ion microscopy, a method of surface microanalysis, is applied to the detection of trace elements in the lung. With this method it is possible to obtain images of the distribution of any element in lung tissue sections with a resolution of 0.5 micron and with very high sensitivity (of an order of magnitude 3 or 4 times greater than with X-ray microanalysis). Under these conditions it is possible to study at the microscopic level the penetration into the lung cells of mineral materials administered in physiological amounts. The images are formed by ion microscopy of atoms sputtered as charged particles from the specimen, and these atoms are selected by mass spectrometry. This technique has been applied to the detection of aerosols (diam. less than 1 micron) of rare earths (thulium or cerium chloride), inhaled in very small amounts (20-50 micrograms), in cells from the lung of a rat. Images of the distribution of these elements were obtained in a few seconds or minutes, when X-ray microanalysis gave either a weak signal or none at all. Their behaviour in the lung could be easily studied several weeks after the end of the inhalation.

Aerosols↗

Studies of nutritional safety of some heavy metals in mice.

Heavy metals have been proposed as nutrient markers to allow the accurate determination of the time of passage, nutrient intake, or apparent utilization of multiple nutrients. In order to evaluate possible toxic effects of scandium, chromium, lanthanum, samarium, europium, dysprosium, terbium, thulium, and ytterbium oxides, and barium sulfate upon growth, general development, reproduction, and lactation, mice were fed different levels of these compounds for three generations. The amount of elements fed were 0,110, 100, and 1000 times the use amount. The use amounts were (in ppm2.) : Sc, 0.12; Cr, 0.02; La.0.40;; Sm. 0.80; Eu, 0.036:TB, 1.20; Dy, 1.20; Tm. 0.08; Tb, 0.12; and Ba, 0.008. The use amount was one-fifth of the concentration required for activation analysis. Mortality and morbidity were negligible. No consistent growth rate changes were observed; however, different groups showed different growth rates during different generations. The number of mice born showed no significant differences amoung treatment groups. Survival, growth rate, hematology, morphological development, maturation, reproduction, and lactational performance were comparable in mice fed the different levels of 10 heavy metal oxides to those mice fed the basal diet.

Animals↗

Thermoluminescent characteristics of LiKYF5:Pr3+ and KYF4:Tm3 crystals for applications in neutron and gamma dosimetry.

Thermoluminescent (TL) properties of two concentration series lithium potassium yttrium fluoride doped with praseodymium (LiKYF5:Pr3+) and potassium yttrium fluoride doped with thulium (KYF4:Tm3+) have been investigated after gamma and neutron irradiation. The main purpose of this research is to see whether these materials are suitable for gamma and/or neutron dosimetry purposes. It has been found that the compounds of both series are sensitive to 60Co gamma radiation. A maximal TL sensitivity is found for LiKY0.99Pr0.01F5 and KY0.99Tm0.01F4. However, for this doping level the intensity of the TL glow peak is about 7 times less than that for LiF:Mg,Ti (TLD-700). The TL sensitivity to thermal neutrons is relatively higher than that to 60Co photons. No TL sensitivity to fast neutrons was observed.

Crystallization↗

Cutting and skin-ablative properties of pulsed mid-infrared laser surgery.

BACKGROUND: Pulsed mid-infrared lasers allow a precise removal of soft tissues with only minimal thermal damage. OBJECTIVE: To study the potential dermatosurgical usefulness of currently available systems at different wavelengths (2010-nm Thulium:YAG laser, 2100-nm Holmium:YAG laser, 2790-nm Erbium:YSGG laser, and 2940-nm Erbium:YAG laser) in vivo on pig skin. METHODS: Immediate effects and wound healing of superficial laser-abrasions and incisions were compared with those of identical control lesions produced by dermabrasion, scalpel incisions, or laser surgery performed by a 1060-nm Nd:YAG and a 1060-nm CO2 laser (continuous and superpulsed mode). RESULTS: Best efficiency and least thermal injury was found for the pulsed Erbium:YAG laser, leading to ablative and incisional lesions comparable to those obtained by dermabrasion or superficial scalpel incisions, respectively. CONCLUSION: In contrast to other mid-infrared lasers tested, the 2940-nm Erbium:YAG laser thus provides a potential instrument for future applications in skin surgery, especially when aiming at a careful ablative removal of delicate superficial lesions with maximum sparing of adjacent tissue structures. However, in the purely incisional application mode pulsed mid-infrared lasers, though of potential usefulness in microsurgical indications (eg, surgery of the cornea), do not offer a suggestive alternative to simple scalpel surgery of the skin.

Aluminum Silicates↗

An analysis of the action of cations of the lanthanide series on the mechanical responses of guinea-pig ileal longitudinal muscle.

1. The inhibitory effects of lanthanide cations (Ln3+) on mechanical responses and 45Ca uptake in guinea-pig ileal longitudinal smooth muscle were studied. 2. Ln3+ strongly inhibited the phasic and tonic component of the response to the muscarinic agonist cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD) the two components being affected to the same extent. Inhibition was also obtained for the responses evoked by high K+ but here the effect was mainly on the phasic response, the tonic component was merely delayed. 3. Other members of the Ln3+ series, with the exception of cerium, were found to be more effective than lanthanum in their ability to inhibit the CD response. Thulium, Tm3+, the thirteenth member of the series was the most effective cation. 4. Analysis of 170Tm uptake revealed at least two components. The concentration-dependence of one component, saturating at 2-5 x 10(-6) Tm, corresponded closely to that of the inhibitory effect of Tm3+ on contraction. 5. 170Tm uptake as a function of time showed a secondary rise after 30 min of exposure to the lanthanide. 6. Although 2-5 x 10(-6) M-Tm3+ produced 90% inhibition of the CD and the high K+ induced responses significant reduction of 45Ca uptake by the muscle was only detected when much higher Tm3+ concentrations (greater than or equal 10(-3) M-Tm3+) were used. 7. It is concluded that Ln3+ combine with membrane sites specifically involved in Ca2+ translocation during excitation-contraction coupling.

Animals↗

Soft tissue effects of the THC:YAG laser on canine vocal cords.

Recently, a laser based on a thulium-holmium-chromium (THC) doped Yttrium-aluminum-garnet (YAG) rod has been developed that produces light of 2.15 microns wavelength and can be transmitted through a low OH- silica fiberoptic cable. This wavelength falls on one of the peaks of the energy absorption spectrum of water. Thus, the THC:YAG laser eliminates the disadvantage of a cumbersome delivery system found in the CO2 laser while still providing precise cutting and minimal tissue injury inherent in lasers emitting light absorbed by water. We evaluated the soft tissue effects of this laser on canine vocal cords. Ablative lesions were produced by the THC:YAG laser and histologically examined on postoperative days 1, 7, and 28. Results indicate that the depth of tissue penetration is easily controlled and the healing response to tissue injury is comparable to that of the CO2 laser. The THC:YAG laser should prove to be a superior laser for use in otorhinolaryngology, especially when adapted to a flexible endoscope.

Aluminum Silicates↗

[Spectroscopic characterization of Tm3+ ions in zinc tungstate crystals].

A series of high quality ZnWO4:Tm3+ single crystals were grown with Czochralski method. The concentrations of thulium ions were 0.1, 0.3, 0.5, 0.7 and 1.0 mol%, respectively. When ZnWO4:Tm3+ single crystals were excited by 807 nm laser, the up-conversion luminescence peaks at 486 and 695 nm which corresponded to transitions 1G4-->3H6 and 3F3-->3 H6, respectively, were detected. The intensity of 695 nm luminescence varied with the pump power in a double logarithmic relation whose indexes were 0.8 and 1.1 orders, respectively.

Crystallization↗

[Digital recording of glow curves of the TLD-300 thermoluminescent dosimetry detector by adaptation of a sum of Gauss function to the measured values].

Calciumfluoride doped with Thulium (TLD-300) can be used to measure simultaneously with one detector neutron and photon absorbed dose in mixed neutron-photon beams. The accuracy in dose measurements can be increased by use of a computer. Additionally the number of data needed to store a glow curve can be reduced from 240 to 24 by fitting a sum of Gauss functions to the measured glow curve.

Calcium Fluoride↗

23Na NMR shift reagents enhance cardiac staircase effect in isolated perfused rat hearts.

The effects of the currently used (23)Na NMR shift reagents, dysprosium bis-triphosphate [Dy(PPP)(2)], dysprosium triethylenetriamine hexaacetate [Dy(TTHA)] and thulium 1,4,7, 10-tetraazacyclododecane-N,N',N",N"'-tetra(methylenephosphonate) [Tm(DOTP)] were studied in the rat heart cardiac staircase model. Rat hearts were perfused with low or normal extracellular free calcium ([Ca(o)](f)). At low [Ca(o)](f) (0.34 +/- 0.05 mM), hearts were perfused with Dy(PPP)(2) (group I), Dy(TTHA) (group II) or no shift reagent (group III), while at normal [Ca(o)](f) (1.25 +/- 0.15 mM), hearts were perfused with Tm(DOTP) (group IV), Dy(TTHA) (group V) or no shift reagent (group VI). Left ventricular developed pressure (LVDP) values in group I were significantly higher than in groups II and III (p < 0.01), while no significant differences were found between groups II and III. LVDP values in group IV were significantly higher than in groups V and VI (p < 0.05), while the LVDP values in groups V and VI were almost identical. Also, a positive correlation between pacing rate and intracellular sodium ([Na(i)]) was evident. The [Na(i)] values at high [Ca(o)](f) were significantly lower than at low [Ca(o)](f) at each pacing level (p <0.01), indicating a negative correlation between [Na(i)] and [Ca(o)](f). No statistical differences were found in [Na(i)] between groups I vs II and IV vs V, showing that determination of [Na(i)] is not affected by any of these shift reagents. Thus the different LVDP responses in groups I vs II and IV vs V were not mirrored in [Na(i)] changes. We hypothesize that a direct, sarcolemmal Ca-Dy(PPP)(2)-, or Ca-Tm(DOTP)-induced positive inotropic effect could be responsible for these Na(i)-independent LVDP increases in groups I and IV.

Animals↗

Preliminary evaluation of a pulsed 2.15-micron laser system for fiberoptic endoscopic surgery.

There is a need for lasers that are compatible with fiberoptic endoscopes and that provide greater cutting precision than currently can be produced by the widely used Nd:YAG (1.06 micron) laser. Recently available lasers that operate in the 2-micron region fill this need. This laser light energy can be transmitted by low OH- silica fibers and has much less tissue penetration than radiation at 1.06 micron. We have been evaluating a prototype solid state laser system that produces pulses of 2.15 microns light that is delivered by a silica based fiberoptic delivery system with negligible transmission losses. This system is based on a thulium-holmium-chromium doped YAG (Tm-Ho-Cr: YAG) rod that lases at 2.15 micron. The laser does not require cryogenic cooling, toxic gases, or custom utilities and should be practical in a clinical environment. In vivo animal testing of this laser confirms that it provides greater ablating precision than does the Nd:YAG laser at 1.06 micron.

Animals↗

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↗

Sutureless microvascular anastomosis using the THC:YAG laser: a preliminary report.

Laser anastomosis of the rat carotid artery was performed using a new mid-infrared laser, the pulsed thulium-holmium-chromium: YAG (THC:YAG) laser (2.15 microns). Solid silicone stents made stay sutures unnecessary for coaptation of vessel edges during laser bonding. Grossly, the laser anastomoses displayed minimal thermal distortion of the vessel contour and no tissue carbonization. Of the 30 anastomoses performed, 27 were patent and 3 had separation of the weld shortly after the approximator clamp was released. Mean anastomotic time was 4 min 48 sec. Mean bursting pressure for the 9 vessels tested was 400 mm Hg. Thrombosis did not occur at any time during our examination of these anastomoses. Fusion of collagen fibers in the media was confirmed histologically. Unlike the CO2 laser, the THC:YAG is transmissible through flexible silica fibers, which greatly facilitates delivery of the laser in a microsurgical operative field. The THC:YAG provides shallower absorption depth than Nd:YAG and argon lasers but somewhat deeper tissue penetration than CO2. For microvessels, this intermediate absorption results in full-thickness fusion of the media, with minimal thermal damage to vascular tissue adjacent to the anastomosis.

Anastomosis, Surgical↗

In vivo sodium chemical shift imaging.

The shift reagents thulium(III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'tetramethylenephosphonate (TmDOTP5-), and dysprosium(III)triethylenetetramine-hexaacetate (DyTTHA3-) are compared in this work for their uses in sodium chemical shift imaging (NaCSI). In a series of experiments using phantoms we evaluated the relative contributions of bulk magnetic susceptibility (BMS) effects and hyperfine shifts to the induced 23Na chemical shift for these two shift reagents. The ratios of BMS effects to hyperfine shifts suggest that TmDOTP5- should be a more effective shift reagent than DyTTHA3- for 23Na NMR spectroscopy as well as NaCSI. The dependence on pH and free Ca2+ concentration of the 23Na NMR frequency shift induced by TmDOTP5- was evaluated. It was found that TmDOTP5- produces good spectral resolution under physiologic conditions. Examples presented from in vivo NaCSI experiments using TmDOTP5- to study diffusion in the posterior chamber of the rabbit eye and to monitor the rate of clearance of aqueous fluid from the anterior chamber demonstrate the effectiveness of this new shift reagent and of the NaCSI technique for in vivo studies.

Animals↗

TmDOTP5-: a substance for NMR temperature measurements in vivo.

The chemical shifts of 31P and 1H in thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) (TmDOTP5-) are approximately two orders of magnitude more sensitive to temperature than are water proton and 19F shifts. In the physiologically relevant pH range, the 31P and 1H chemical shifts of TmDOTP5- are linear functions of temperature between 25 and 47 degrees C. The results indicate that using TmDOTP5- can provide measurements of temperature in vivo that are significantly more accurate than methods based on water and fluorocarbon chemical shifts.

Abdomen↗

Noninvasive MR thermometry using paramagnetic lanthanide complexes of 1,4,7,10-tetraazacyclodoecane-alpha,alpha',alpha'',alpha'''-tetramethyl-1,4,7,10-tetraacetic acid (DOTMA4-).

Noninvasive techniques to monitor temperature have numerous useful biomedical applications. However, MR thermometry techniques based on the chemical shift, relaxation rates, and molecular diffusion rate of the water 1H signal suffer from poor thermal resolution. The feasibility of MR thermometry based on the strong temperature dependence of the hyperfine-shifted 1H signal from the paramagnetic lanthanide complex thulium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTA-) was recently demonstrated. The use of paramagnetic lanthanide complexes for MR thermometry can be further enhanced by improving the signal-to-noise ratio (SNR) of the observed signal. In this study, the use of lanthanide complexes of a methyl-substituted analog of DOTA4-, 1,4,7,10-tetramethyl 1,4,7,10-tetra azacyclodoecane-1,4,7,10-tetraacetic acetate (DOTMA4-) was evaluated. DOTMA4- complexes have 12 magnetically equivalent methyl protons, which provide an intense and sharper resonance compared to the corresponding DOTA- complexes. Experiments with paramagnetic Pr3+, Yb3+, Tb3+, Dy3+, and Tm3+ complexes of DOTMA4- showed that the Tm3+ complex is most favorable for MR thermometery because of the high temperature dependence of its chemical shift and its relatively narrow linewidth. The chemical shift of the methyl 1H signal from TmDOTMA- was approximately 60 times more sensitive to temperature than the water 1H shift and was insensitive to changes in concentration, pH, [Ca2+], or the presence of other ions and macromolecules. The application of TmDOTMA- for measuring temperature in a subcutaneously implanted tumor model was demonstrated. Lastly, the feasibility of obtaining 3D images from the methyl 1H resonance of TmDOTMA- was demonstrated in phantom and live animal experiments. Overall, TmDOTMA- appears to be a promising probe for MR thermometry in vivo.

Algorithms↗

Simultaneous measurements of temperature and pH in vivo using NMR in conjunction with TmDOTP5-.

NMR techniques for temperature and pH measurements have attracted increasing interest in recent years, motivated in part by the growing importance of medical hyperthermia for the treatment of cancer. The chemical shifts of thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetrakis(methylene phosphonate) (TmDOTP5-) have been studied as a function of temperature and pH. The results demonstrate that TmDOTP5- resonance shifts are highly sensitive to temperature (approximately 1.0 ppm/degrees C) and pH (approximately 3.2 ppm/pH unit) at clinically relevant field strengths. A new method is presented which utilizes two magnetically non-equivalent protons in TmDOTP5- for simultaneous NMR measurements of both temperature and pH. The difference in the chemical shift values of pairs of 1H resonances provides a temperature sensitivity of about 1.6 ppm/ degrees C. The technique is demonstrated in live rats undergoing ultrasound-induced hyperthermia therapy.

Animals↗

TmDOTA-: a sensitive probe for MR thermometry in vivo.

The lanthanide complex, thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (TmDOTA-), has been investigated as an agent for MR thermometry in vivo. The chemical shifts of the TmDOTA- protons were highly sensitive to temperature at a clinically relevant field strength, yet insensitive to pH and the presence of Ca2+. Given the excellent stability of lanthanide-DOTA complexes and high thermal sensitivity, TmDOTA- is expected to be a good candidate for MR thermometry in vivo.

Animals↗