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Biomedical subjects

W S Grundfest

Publications and source records attributed to W S Grundfest.

At least 19 recordsLinked to original sources

Excimer laser (308 nm) based transmyocardial laser revascularization: effects of the lasing parameters on myocardial histology.

BACKGROUND AND OBJECTIVE: The effect of the excimer laser (308 nm) parameters on transmyocardial revascularization (TMR) channels is not well defined. This study investigates the influence of the pulse repetition rate, the size of the delivery catheter and its advancement speed on the morphology of TMR channels in vivo. STUDY DESIGN/MATERIALS AND METHODS: Myocardial ablation was performed in a porcine model (N = 27) using multifiber catheters of 1.0 and 1.4 mm in diameter. The catheters were advanced into the myocardium at different speeds (1.27 and 2.54 mm/sec) while ablating at various repetition rates (10-80 Hz). The radiant exposure was kept at 35 mJ/mm(2) throughout the experiments. The channel histology was quantified by digital microscopy. RESULTS: The channel cross-sectional area and the extent of the thermal damage decrease as the catheter advancement speed exceeds the ablation speed and vice versa. Within the parameters tested, advancement speed of about 1.3 mm/sec and pulse repetition rates of 40 Hz produce channels of size comparable to the catheter's diameter with moderate thermomechanical damage. CONCLUSIONS: The repetition rate, catheter size, and catheter advancement speed are closely intertwined and crucial to the histological outcome of excimer laser based TMR.

Animals↗

Excimer laser (308 nm) recanalisation of in-stent restenosis: thermal considerations.

Excimer laser recanalisation of in-stent restenosis may be a viable modality for improving coronary patency. However, the presence of arterial stents modifies the thermal properties of the irradiated area and may alter temperature patterns generated during ablation. The goal of this study was to evaluate, in vitro, temperature changes during excimer laser ablation of stented vessels and compare them with those obtained from unstented (control) vessels. Six different stent types (AVE Microstent-II, AVE-GFX, ACS Multi-link, JJ Palmaz-Schatz, JJ Crown, and NIR) were deployed in freshly excised porcine coronary vessels. Three control unstented samples were also measured. Blood or saline was infused through the vessels, while the tissue environment was kept at approximately 37 degrees C. A 308 nm excimer laser (Spectranetics, CVX300) with an eccentric 2.0 mm laser catheter (Spectranetics, EII) delivered two trains of 200 pulses each, 10 s apart, at 60 mJ/mm2, and 40 Hz, simulating maximum clinical exposure. The catheter was positioned midway in the stent, first coaxially parallel to the vessel wall, and then at an angle against the stent and vessel wall. Temperature measurements (n= 168 for blood, n=96 for saline) were performed with a approximately 210 microm diameter, fast-response thermocouple with 0.1 degrees C resolution. The probe was positioned to within approximately 250 microm from the inner surface of the vessels. Tissue temperature was measured at the catheter tip and at the distal and proximal edges of the stents. Maximum recorded temperatures for coaxial and angular alignment, did not exceed 42.2 degrees C (approximately 6 degrees C above baseline) and 54.2 degrees C (approximately 18.1 degrees C above baseline) respectively, for all stents types tested, controls, and all probe locations. Both stented and unstented vessels exhibited comparable temperature gradients. The observed maximum temperatures, obtained under extreme lasing conditions, indicated that 308 nm ablation, in the presence of stents under blood or saline infusion, produces clinically acceptable temperatures.

Angioplasty, Laser↗

Discrimination of human coronary artery atherosclerotic lipid-rich lesions by time-resolved laser-induced fluorescence spectroscopy.

Lesion composition plays a significant role in atherosclerotic lesion instability and rupture. Current clinical techniques cannot fully characterize lesion composition or accurately identify unstable lesions. This study investigates the use of time-resolved fluorescence spectroscopy for unstable atherosclerotic lesion diagnosis. The fluorescence of human coronary artery samples was induced with nitrogen laser and detected in the 360- to 510-nm wavelength range. The samples were sorted into 7 groups according to the AHA classification: normal wall and types I, II(a) (fatty streaks), III (preatheroma), IV (atheroma), V(a) (fibrous), and V(b) (calcified) lesions. Spectral intensities and time-dependent parameters [average lifetime tau(f); decay constants: tau(1) (fast-term), tau(2) (slow-term), A(1) (fast-term amplitude contribution)] derived from the time-resolved spectra of coronary samples were used for tissue characterization. We determined that a few intensity values at longer wavelengths (>430 nm) and time-dependent parameters at peak emission region (390 nm) discriminate between all types of arterial samples except between normal wall and type I lesions. The lipid-rich lesions (more unstable) can be discriminated from fibrous lesions (more stable) on the basis of time-dependent parameters (lifetime and fast-term decay). We inferred that features of lipid fluorescence are reflected on lipid-rich lesion emission. Our results demonstrate that analysis of the time-resolved spectra may be used to enhance the discrimination between different grades of atherosclerotic lesions and provide a means of discrimination between lipid-rich and fibrous lesions.

Adolescent↗

Time-resolved fluorescence of human aortic wall: use for improved identification of atherosclerotic lesions.

BACKGROUND AND OBJECTIVE: This study characterized aortic time-resolved fluorescence spectra for stratified levels of atherosclerosis and proposed interpretation of spectrotemporal variations in terms of histologic changes. STUDY DESIGN/MATERIALS AND METHODS: Fluorescence emission transients were measured at 370-510 nm (337 nm excitation) on 94 excised human aortic samples, ranging from normal to advanced fibrous atherosclerotic lesion. Global analysis yielded a three-exponential approximation of the time-resolved spectra from which average lifetime and decay-associated spectra were derived. RESULTS: Average lifetime at 390 nm gradually increased from 2.4+/-0.1 nsec (normal aorta) to 3.9+/-0.1 nsec (advanced lesion). Fluorescence intensity was markedly decreased above 430 nm in intermediate and advanced lesions. Spectral intensity associated with the intermediate decay increased at 470-490 nm for early and intermediate lipid-rich lesions. CONCLUSION: Time-resolved fluorescence spectra of aortic samples presented distinctive features for each atherosclerotic lesion type, which could serve as characteristic markers for optical analysis of the aortic wall.

Adolescent↗

Laser tissue interaction in direct myocardial revascularization.

This investigation examines the various laser choices used for transmyocardial laser revascularization (TMLR) with emphasis on the laser-tissue interaction. A series of in vivo (porcine model, n=27) and in vitro experiments were performed to study the effects of CO(2), holmium:YAG, and XeCl excimer lasers on the histological outcome of TMR channels. Computerized histopathological analysis has revealed that the CO(2) and holmium:YAG lasers produce substantial unpredictable thermal damage and differ predominantly in the amount of the mechanical injury or tissue shredding. In comparison, the excimer laser appears to produce the most uniform tissue ablation with the least thermal and shockwave damage.

Animals↗

Laser induced fluorescence attenuation spectroscopy: detection of hypoxia.

The development of a new laser-induced fluorescence (LIF) spectroscopy technique for the measurement of the attenuation spectrum of tissue is described. The technique, termed laser-induced fluorescence attenuation spectroscopy (LIFAS), has been applied to study the effects of hypoxia on the in vivo optical properties of renal and myocardial tissue in the 350-600-nm band. Excimer laser (Xe-Cl) is used to excite a small volume of the tissue (rabbit model, N = 20) and induce autofluorescence. The emitted LIF is monitored fiberoptically at two locations that are unevenly displaced about the fluorescing volume. The optical attenuation of the tissue is calculated from the dual LIF measurements by assuming an exponential decay of the fluorescence with distance. The results indicate that hypoxia modulates the attenuation spectrum leading to characteristic changes in its shape. Primarily, the spectral profile becomes more concave between 455 nm and 505 nm and two spectral peaks at about 540 and 580 nm disappear leaving in their place a single peak at about 555 nm. The attenuation spectra of normoxic and hypoxic tissue are used to train partial least squares multivariate model for spectral classification. The model detected acute renal and myocardial hypoxia with an accuracy greater than 90% (range: 90%-96%) and 74% (range: 74%-90%), respectively.

Animals↗

Consequences of scattering for spectral imaging of turbid biologic tissue.

Spectral imaging permits two-dimensional mapping of the backscattering properties of biological systems. Such mapping requires broadband illumination of the entire area of interest. However, imaging of turbid biological media under these conditions often involves mean photon path lengths that exceed the pixel size. Using a numerical Monte Carlo model, we have studied the effects of photon scattering in a hemoglobin-bearing model system. We find that photon migration and the resulting wavelength-dependent optical coupling between pixels can complicate the analysis of imaging spectroscopy data. In fact, the wavelength dependence of photon trajectories also alters the distribution of photon exit angles at the tissue surface. We therefore find that the finite optical field of view of an imaging spectrometer can affect the measured spectra in the absence of chromatic aberrations.

Hemoglobins↗

Time-resolved fluorescence spectra of arterial fluorescent compounds: reconstruction with the Laguerre expansion technique.

The time-resolved fluorescence spectra of the main arterial fluorescent compounds were retrieved using a new algorithm based on the Laguerre expansion of kernels technique. Samples of elastin, collagen and cholesterol were excited with a pulsed nitrogen laser and the emission was measured at 29 discrete wavelengths between 370 and 510 nm. The expansion of the fluorescence impulse response function on the Laguerre basis of functions was optimized to reproduce the observed fluorescence emission. Collagen lifetime (5.3 ns at 390 nm) was substantially larger than that of elastin (2.3 ns) and cholesterol (1.3 ns). Two decay components were identified in the emission decay of the compounds. For collagen, the decay components were markedly wavelength dependent and hydration dependent such that the emission decay became shorter at higher emission wavelengths and with hydration. The decay characteristics of elastin and cholesterol were relatively unchanged with wavelength and with hydration. The observed variations in the time-resolved spectra of elastin, collagen and cholesterol were consistent with the existence of several fluorophores with different emission characteristics. Because the compounds are present in different proportions in healthy and atherosclerotic arterial walls, characteristic differences in their time-resolved emission spectra could be exploited to assess optically the severity of atherosclerotic lesions.

Arteries↗

Photobleaching of arterial fluorescent compounds: characterization of elastin, collagen and cholesterol time-resolved spectra during prolonged ultraviolet irradiation.

To study the photobleaching of the main fluorescent compounds of the arterial wall, we repeatedly measured the time-resolved fluorescence of elastin, collagen and cholesterol during 560 s of excitation with nitrogen laser pulses. Three fluence rate levels were used: 0.72, 7.25 and 21.75 microW/mm2. The irradiation-related changes of the fluorescence intensity and of the time-resolved fluorescence decay constants were characterized for the emission at 390, 430 and 470 nm. The fluorescence intensity at 390 nm decreased by 25-35% when the fluence delivered was 4 mJ/mm2, a common value in fluorescence studies of the arterial wall. Cholesterol fluorescence photobleached the most, and elastin fluorescence photobleached the least. Photobleaching was most intense at 390 nm and least intense at 470 nm such that the emission spectra of the three compounds were markedly distorted by photobleaching. The time-resolved decay constants and the fluorescence lifetime were not altered by irradiation when the fluence was below 4 mJ/mm2. The spectral distortions associated with photobleaching complicate the interpretation of arterial wall fluorescence in terms of tissue content in elastin, collagen and cholesterol. Use of the time-dependent features of the emission that are not altered by photobleaching should increase the accuracy of arterial wall analysis by fluorescence spectroscopy.

Animals↗

Safety evaluation of laparoscopically applied clips.

We have evaluated in vitro, the security of laparoscopically applied clips, through two commercially available clip appliers: the Endo Clip II (US Surgical) and the Ligaclip (Ethicon). The clip performance was tested with respect to dislodgment and leakage. Dislodgment was attempted both transversely and at 45 degrees with respect to the main axis of the tubular structures tested. The mean maximum force (N = 24) necessary to dislodge a clip applied to silicone tubing (2.1, 2.4, 3.2 mm o.d.) and porcine vascular tissue was measured. The maximum force needed to transversely dislodge a clip applied to silicone tubing, ranged from 262 +/- 9 g (2.1 mm) to 315 +/- 11 g (3.2 mm) for the Endo Clip II applier, while the values for the Ligaclip were 220 +/- 28 g (2.1 mm) and 273 +/- 11 g (3.2 mm), respectively. To achieve dislodgment at 45 degrees pull, corresponding forces of 294 +/- 8 g (2.1 mm) and 369 +/- 14 g (3.2 mm) for the Endo Clip II, and 254 +/- 14 g (2.1 mm) and 297 +/- 13 g (3.2 mm) for the Ligaclip (N = 24) were required. Transverse dislodgment forces, for clips applied to tissue, were 556 +/- 146 g for the Endo Clip II and 356 +/- 170 for the Ligaclip (N = 6). Leakage tests were also performed under pulsatile blood circulation at mean pressure of approximately 800 mm Hg. No tested clips applied to either silicone tubing or tissue allowed for any blood leakage. The dislodgment test showed that the Endo Clip II exhibits superior performance compared to the Ligaclip, based on the fact that it requires more force for transverse and semiaxial dislodgment. In the leakage test, both clip appliers performed equivalently.

Animals↗

Spectro-temporal studies of Xe-Cl excimer laser-induced arterial wall fluorescence.

We report on spectro-temporal fluorescence studies of cadaver femoral arterial walls at different stages in the progression of atherosclerosis. After excitation with a Xe-Cl excimer pulse, the time course of the fluorescence spectrum was recorded over time, and time-resolved multispectral analysis was performed. Then, under the assumption of linearity, we derived a linear spectro-temporal kernel (a weighting function) which describes the temporal behavior of the fluorescence process independently of the pulse width of the photoexcitation. The data analysis revealed both static and dynamic fluorescence characteristics which exhibited a good correlation with histological findings.

Arteriosclerosis↗

Photodynamic therapy for the treatment of squamous cell carcinoma using benzoporphyrin derivative.

BACKGROUND: Photodynamic therapy (PDT) involves laser light excitation of a tumor-localizing photosensitizer to destroy neoplasms. Benzoporphyrin derivative (BPD) is a new photosensitizer with several favorable characteristics. OBJECTIVE: Studies were designed to: 1) assess the efficacy of BPD-mediated PDT in treating in vivo squamous cell carcinomas (SCC); 2) obtain dosimetry data for BPD and laser parameters; and 3) establish clinical and histologic correlates of BPD-induced tumor regression. METHODS: Human SCC was implanted into nude mice. One group received BPD followed by laser light of 150 J/cm2 from an argon-pumped dye laser at 690 nm. Three control groups included laser energy alone, BPD alone, and no treatment. RESULTS: At day 21 posttreatment only PDT-treated tumors showed a statistically significant decrease in tumor volume and complete cure rate. Clinical resolution (scar) correlated perfectly with histologic resolution (scar). CONCLUSION: Human SCC in a nude mouse model responds to BPD-mediated PDT.

Anaplasia↗

Effect of varying laser parameters on pulsed Ho:YAG ablation of bovine knee joint tissues.

We investigated the effect of varying laser parameters on ablation of fresh bovine knee joint tissues (fibrocartilage, hyaline cartilage, and bone) with a free-running Ho:YAG laser. Ablation rate was measured in saline for each tissue type as a function of laser fluence (160-950 J/cm2), pulse width (150-450 microseconds, full width at half maximum), and fiber core diameter (400 and 600 microns). A weight that was attached to the fiber end was used to exert a constant pressure of 40 g/mm2 to the tissue underneath to ensure a constant contact between the fiber tip and the tissue throughout the ablation process. All tissues could be efficiently ablated, and the ablation rate increased linearly with the fluence. Change in laser pulse width and fiber core diameter resulted in minor variations in the ablation rate for fibro- and hyaline cartilage. On the other hand, use of longer pulses and/or the larger fiber significantly accelerated bone ablation. Histology analysis revealed that zones of thermal damage in Ho:YAG irradiated bovine knee joint tissues differed by tissue types and ranged between 100 and 400 microns, but were independent of fluence, pulse width, and fiber size within the range tested.

Animals↗

Endoscopy of the lacrimal outflow system.

Management of obstructions in the lacrimal drainage system would be greatly aided by improvements in the ability to visualize the blockages. We describe a new method of observation using miniature fiberoptics to view the entire lacrimal excretory system. We employed flexible endoscopes of fiberoptic bundles with outside diameters of from 0.5 to 0.7 mm. These endoscopes were inserted through the puncta and canaliculi. Sixteen patients were examined. A range of pathologic conditions were found, including slightly stenosed passages and severely destroyed canalicular mucosal lining. Our results indicate that this technique is feasible and useful in the diagnosis of lacrimal excretory disease.

Endoscopes↗

Falloposcopic classification and treatment of fallopian tube lumen disease.

OBJECTIVE: To devise a diagnostic classification and scoring system for tubal lumen disease based on falloposcopy and to evaluate it against tuboplasty procedures and pregnancy outcomes. DESIGN: Prospective study approved by the hospital Institutional Review Board. SETTING: Academic tertiary infertility center. PATIENTS: Seventy-five women with hysterosalpingographic and laparoscopic evidence of endotubal disease had 112 tubes available for falloposcopic evaluation. INTERVENTION: Diagnostic and operative falloposcopy was performed, when indicated, using aquadissection, flexible wire cannulation, or direct balloon tuboplasty. RESULTS: The endotubal lumens were considered to be falloposcopically normal in 52 tubes (46%), to contain mild to moderate disease in 33 (29%), and severe to obstructive disease in 27 (25%) cases. Within a year of the procedure, 6 of the 28 women (21%) in whom at least 1 tube was normal conceived, in 2 of 22 (9%) with mild to moderate disease, and in 0 of 16 (0%) with severe endotubal disease. CONCLUSIONS: Falloposcopy provides a visual means of scoring endotubal disease and may be intrinsically therapeutic for dislodging intraluminal debris and breaking down filmy adhesions in normal or minimally diseased tubes. The presence of severe disease remains resistant to the use of current endotuboplasty treatments as reflected by poor pregnancy outcome, and such women should be provided the option of microsurgical tubal repair or in vitro fertilization and embryo transfer procedures.

Adult↗