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Biomedical subjects

K T Schomacker

Publications and source records attributed to K T Schomacker.

27 records · Page 2Linked to original sources

Laser induced autofluorescence diagnosis of bladder cancer.

PURPOSE: We assessed the ability of laser induced autofluorescence to differentiate malignant from nonmalignant bladder lesions. MATERIALS AND METHODS: We studied 53 patients with bladder cancer undergoing mucosal biopsies or transurethral resection of a bladder tumor. A quartz optical fiber was advanced through the working channel of a cystoscope and placed in gentle contact with the bladder. Tissue fluorescence was excited by 337 nm. light pulses (nitrogen laser). One fiber was used for transmission of the excitation and emission (fluorescence) light. An optical multichannel analyzer system was used to record fluorescence spectra of the sites of interest. RESULTS: We analyzed the fluorescence spectra of 114 bladder areas (1 carcinoma in situ as well as 28 malignant, 35 inflammatory, 7 dysplastic, 1 squamous metaplastic and 42 normal areas). These lesions included 44 difficult to diagnose suspicious tumors (11 malignant and 33 nonmalignant). We developed an algorithm that used the I385:I455 nm. fluorescence ratio to distinguish malignant from nonmalignant lesions, including inflammatory areas. By analyzing the data on all 114 lesions, we noted the sensitivity, specificity, and positive and negative predictive values of this method for differentiating malignant from nonmalignant bladder lesions to be 97, 98, 93 and 99%, respectively. CONCLUSIONS: Under excitation with 337 nm. light a clear differentiation between malignant and nonmalignant bladder tissues can be made using the I385:I455 nm. autofluorescence ratio.

Aged↗

Intraoperative myocardial ischemia detection with laser-induced fluorescence.

Myocardial ischemia can be detected at the mitochondrial level by measuring shifts in nicotinamide adenine dinucleotide and its reduced form. Using a pulsed nitrogen laser and an optical multichannel analyzer, we monitored myocardial metabolism by measuring laser-induced nicotinamide adenine dinucleotide (reduced form) fluorescence in a large animal model of acute ischemia. Eight opened-chest sheep underwent occlusion of branches of the left anterior descending coronary artery, establishing a 15% infarct of the left ventricle. For the simulation of the clinical scenario, after 60 minutes of occlusion, the animals were supported by cardiopulmonary bypass, the aorta was crossclamped, and cold crystalloid cardioplegic solution was administered. The occlusion was removed after 10 minutes, and two additional doses of cardioplegic solution were delivered at 10-minute intervals. The aortic crossclamp was released, and a 30-minute period of reperfusion on bypass ensued. The hearts were then weaned off bypass and allowed to recover. Laser-induced fluorescence was measured inside, outside, and along the border of the infarct. Baseline measurements were made before occlusion, immediately after occlusion, and then at 5, 10, and 20 minutes after occlusion. The results show that immediately after occlusion there is a 200% +/- 30% (mean +/- standard deviation) increase in laser-induced fluorescence in the infarct zone, a 110% +/- 30% increase along the border, and no significant change in the area outside the infarct. The fluorescence in the infarct reaches a plateau in 5 minutes at 270% +/- 30%, whereas along the border it reaches a peak near end ischemia of 110% +/- 40%. With the first dose of cardioplegic solution, fluorescence increases outside the infarct and decreases inside the infarct and along the border to 120% +/- 30%, where it remains for all areas until the aortic crossclamp is removed. Fluorescence then drops to 70% +/- 20% and finally returns to baseline after 5 minutes of recovery. All of these shifts in laser-induced fluorescence were statistically significant (p < 0.01). The changes noted with doses of cardioplegic solution reflect the hypothermic and hyperkalemic effects on the myocardium. Laser-induced fluorescence provides a sensitive and specific method of monitoring myocardial ischemia during the operation. It also provides instantaneous feedback of metabolic changes that may be useful in evaluating the effects of different cardioplegic regimens and in monitoring reperfusion injury.

Animals↗

Pharmacokinetics of a fluorescent drug using laser-induced fluorescence.

Laser-induced fluorescence has been used to measure tissue levels of chloroaluminum sulfonated phthalocyanine in vivo in an implanted hamster cheek pouch carcinoma tumor model. The drug was excited at 610 nm via a pulsed nitrogen laser-pumped dye laser, and fluorescence intensity was monitored at 684 nm for up to 30 days after drug administration. Data were acquired noninvasively with high temporal and spatial resolution using the laser-induced fluorescence apparatus and were analyzed with a multicompartment pharmacokinetic model. In addition, our published data on a C6-BAG glioma rat brain tumor model were analyzed to illustrate the effect of different tumor models on the rates. The rates extracted from the pharmacokinetic model elucidate the mechanisms of drug uptake and retention in the cheek pouch and brain tumor models. The laser-induced fluorescence approach should lead to better drug dosimetry for photochemotherapy and allow quick characterization of the pharmacokinetics of new photosensitizers in tissue.

Animals↗

Chloroaluminum sulfonated phthalocyanine partitioning in normal and intimal hyperplastic artery in the rat. Implications for photodynamic therapy.

Photodynamic therapy, the light activation of photosensitizers into cytotoxic mediators, has been a successful treatment for experimental intimal hyperplasia (IH). To understand the basis of the photosensitizer chloroaluminum sulfonated phthalocyanine (CASPc)-mediated photoinhibition of intimal hyperplasia in the rat common carotid artery model, we studied photosensitizer partitioning in hyperplastic as compared to normal arterial tissue. Serum clearance of CASPc is exponential with, a half-life of 300 minutes. Laser-induced fluorescence and spectrofluorimetric analyses of artery tissue demonstrated an approximately 60% lower uptake and retention of CASPc by normal arterial tissue as compared to arteries with IH; the differences become more pronounced at 24 h. Fluorescent microscopy of arterial tissue demonstrated increased uptake of the CASPc by the artery with IH. However, by 24 h it is primarily the IH tissue that has retained the CASPc, with clearance of the dye from the media of normal or hyperplastic arteries. These data demonstrate that IH, like neoplastic tissue, has an increased accumulation of CASPc compared to normal artery. The preferential partitioning into hyperplastic tissue has implications for therapeutic targeting of this cellular population with photodynamic therapy.

Animals↗

Ultraviolet laser-induced fluorescence of colonic tissue: basic biology and diagnostic potential.

Laser-induced fluorescence (LIF) of colonic tissue was examined both in vitro and in vivo to assess the ability of the technique to distinguish neoplastic from hyperplastic and normal tissue and to relate the LIF spectra to specific constituents of the colon. Spectra from 86 normal colonic sites, 35 hyperplastic polyps, 49 adenomatous polyps, and 7 adenocarcinomas were recorded both in vivo and in vitro. With 337-nm excitation, the fluorescence spectra all had peaks at 390 and 460 nm, believed to arise from collagen and NADH, and a minimum at 425 nm, consistent with absorption attributable to hemoglobin. The spectra of colonic tissue recorded both in vivo and in vitro are different, primarily in the NADH fluorescence component, which decays exponentially with time after resection. When normal colonic tissue is compared to hyperplastic or adenomatous polyps, the predominant changes in the fluorescence spectra are a decrease in collagen fluorescence and a slight increase in hemoglobin reabsorption. A multivariate linear regression (MVLR) analysis was used to distinguish neoplastic tissue from non-neoplastic tissue with a sensitivity, specificity, predictive value positive, and predictive value negative toward neoplastic tissue of 80%, 92%, 82%, and 91%, respectively. When the MVLR technique was used to distinguish neoplastic polyps from non-neoplastic polyps, values of 86%, 77%, 86%, and 77% respectively, were obtained. The data suggest that the LIF measurements sense changes in polyp morphology, rather than changes in fluorophores specific to polyps, and it is this change in morphology that leads indirectly to discrimination of polyps.

Adenocarcinoma↗

Laser-induced fluorescence: experimental intraoperative delineation of tumor resection margins.

The ability of laser-induced fluorescence spectroscopy to delineate tumor margins intraoperatively was studied using a rat intracerebral glioma model. A fluorescent dye, chloro-aluminum phthalocyanine tetrasulfonate (ClAlPcS4), was injected intravenously 24 hours before tumor resection. The animals underwent tumor resection under the operating microscope, guided by laser-induced fluorescence measurement in one group (Group 1) and visual assessment in the other (Group 2). The Group 1 rats had a significantly reduced volume of residual tumor following resection (0.5 +/- 0.2 cu mm vs. 13.7 +/- 4.0 cu mm, mean +/- standard error of the mean, p less than 0.02). Three of the nine animals in Group 1 were tumor-free at 2 weeks following resection, compared with none of the 10 rats in Group 2 (p less than 0.05). Interference from brain autofluorescence was minimized using spectrally resolved detection and the ClAlPcS4 dye, which has a 680-nm fluorescence peak significantly higher than the 470-nm autofluorescence peak of normal brain. Contrast ratios of up to 40:1 were found for glioma:normal brain fluorescence signals. Spatially-resolved spectra were acquired in approximately 5 seconds using a fiberoptic probe. This study demonstrates the ability of an intraoperative laser-induced fluorescence system to detect tumor margins that could not be identified with the operating microscope.

Animals↗

Ultraviolet laser-induced fluorescence of colonic polyps.

Ultraviolet laser-induced fluorescence was examined in vivo to determine whether the technique can reliably distinguish between hyperplastic and adenomatous polyps of the colon. Spectra from 86 normal colonic sites, 35 hyperplastic polyps, and 49 adenomatous polyps were recorded in vivo. Polyp type was independently determined by two senior pathologists who were unaware of the fluorescence measurement. A multivariate linear regression analysis was used to differentiate spectra from hyperplastic and adenomatous polyps and resulted in a sensitivity, specificity, predictive value positive, and predictive value negative for identifying adenomatous polyps of 86%, 80%, 86%, and 80%, respectively. These values were not significantly different from the accuracy of routine clinical pathology. Thus, ultraviolet laser-induced fluorescence appears to show promise as a means for distinguishing tissue types. However, further experience is needed before its routine clinical use can be recommended. Significant changes in the fluorescence spectra occurred postmortem, suggesting that future studies of laser-induced fluorescence of colonic tissue must use data acquired in vivo.

Aged↗

Co:MgF2 laser ablation of tissue: effect of wavelength on ablation threshold and thermal damage.

The wavelength dependence of the ablation threshold of a variety of tissues has been studied by using a tunable pulsed Co:MgF2 laser to determine how closely it tracks the optical absorption length of water. The Co:MgF2 laser was tuned between 1.81 and 2.14 microns, a wavelength region in which the absorption length varies by a decade. For soft tissues the ablation threshold tracks the optical absorption length; for bone there is little wavelength dependence, consistent with the low water content of bone. Thermal damage vs. wavelength was also studied for cornea and bone. Thermal damage to cornea has a weak wavelength dependence, while that to bone shows little wavelength dependence. Framing-camera pictures of the ablation of both cornea and liver show explosive removal of material, but differ as to the nature of the explosion.

Animals↗

Thermal damage produced by high-irradiance continuous wave CO2 laser cutting of tissue.

Thermal damage produced by continuous wave (cw) CO2 laser ablation of tissue in vitro was measured for irradiances ranging from 360 W/cm2 to 740 kW/cm2 in order to investigate the extent to which ablative cooling can limit tissue damage. Damage zones thinner than 100 microns were readily produced using single pulses to cut guinea pig skin as well as bovine cornea, aorta, and myocardium. Multiple pulses can lead to increased damage. However, a systematic decrease in damage with irradiance, predicted theoretically by an evaporation model of ablation, was not observed. The damage-zone thickness was approximately constant around the periphery of the cut, consistent with the existence of a liquid layer which stores heat and leads to tissue damage, and with a model of damage and ablation recently proposed by Zweig et al.

Animals↗