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Light has been used to non-invasively alter the excitability of both neural and cardiac tissue. Recently, pulsed laser light has been shown to be capable of eliciting action potentials in peripheral nerves and in cultured cardiomyocytes. Here, for the first time, we demonstrate optical pacing of an intact heart in vivo. Pulsed 1.875-µm infrared laser light was used to lock the heart rate to the pulse frequency of the laser. A laser Doppler velocimetry signal was used to verify the pacing. At low radiant exposures, embryonic quail hearts were reliably paced in vivo without detectable damage to the tissue, indicating that optical pacing has great potential as a tool with which to study embryonic cardiac dynamics and development. In particular, optical pacing can be used to control the heart rate, thereby altering stresses and mechanically transduced signalling. [ABSTRACT FROM AUTHOR]

A survey of biophysical and biomedical applications of free-electron lasers (FELs) is presented. FELs are pulsed light sources, collectively operating from the microwave through the x-ray range. This accelerator-based technology spans gaps in wavelength, pulse structure, and optical power left by conventional sources. FELs are continuously tunable and can produce high-average and high-peak power. Collectively, FEL pulses range from quasicontinuous to subpicosecond, in some cases with complex superpulse structures. Any given FEL, however, has a more restricted set of operational parameters. FELs with high-peak and high-average power are enabling biophysical and biomedical investigations of infrared tissue ablation. A midinfrared FEL has been upgraded to meet the standards of a medical laser and is serving as a surgical tool in ophthalmology and human neurosurgery. The ultrashort pulses produced by infrared or ultraviolet FELs are useful for biophysical investigations, both one-color time-resolved spectroscopy and when coupled with other light sources, for two-color time-resolved spectroscopy. FELs are being used to drive soft ionization processes in mass spectrometry. Certain FELs have high repetition rates that are beneficial for some biophysical and biomedical applications, but confound research for other applications. Infrared FELs have been used as sources for inverse Compton scattering to produce a pulsed, tunable, monochromatic x-ray source for medical imaging and structural biology. FEL research and FEL applications research have allowed the specification of spin-off technologies. On the horizon is the next generation of FELs, which is aimed at producing ultrashort, tunable x rays by self-amplified spontaneous emission with potential applications in biology. [ABSTRACT FROM AUTHOR]

To evaluate the effect of treatment on forearm rotation, torque muscle strength can be assessed using an isokinetic device (IKD) or a wrist dynamometer (WD). The aims of this study were 1) to determine concurrent validity and intra- and inter-rater reliability using the WD, and to examine correlations between WD and IKD in different positions; and 2) subsequently, to establish the intermethod reproducibility between WD as a handheld (HHD) or fixed device. We conducted a cross-sectional study in which torque strength was measured in healthy participants by two observers using an IKD and a WD. Study endpoints were concurrent validity (Pearson's r), intra- and inter-rater reliability, intermethod reproducibility (intraclass correlation coefficient: ICC) and measurement error (limits of agreement: LoA). Concurrent validity ranged, in the 2 studies assessing it, from r 0.37 to 0.52 for pronation and from r 0.50 to 0.82 for supination, with wide 95% confidence intervals. ICC for intra-rater reliability for pronation ranged from 0.85 to 0.91 and for supination from 0.91 to 0.95. ICC for inter-rater reliability for pronation ranged from 0.84 to 0.96 and for supination from 0.92 to 0.96. Despite the excellent intra- and inter-rater reliability and intermethod reproducibility for the WD-HHD and fixed WD, validity was low when compared to IKD and wide LoA indicated a high measurement error of approximately 20%. These results suggest that the WD cannot replace the IKD isometric mode for pronation and supination. LEVEL OF EVIDENCE: 2., (Copyright © 2022 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

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.

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.

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.

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.

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.

The shielding effectiveness of laser-induced breakdown from focused, visible laser pulses from 5 ns to 125 fs is determined from measurements of transmission of energy through the focal volume. The shielding efficiency decreases as a function of pulse duration from 5 ns to 300 fs and increases from 300 fs to 125 fs. The results are compared with past studies at similar pulse durations. The results of the measurements support laser-induced breakdown models and may lead to an optimization of laser-induced breakdown in ophthalmic surgery by reduction of collateral effects.

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.

Because of the high absorption of near-infrared laser radiation in biological tissue, erbium lasers and holmium lasers emitting at 3 and 2 µm, respectively, have been proven to have optimal qualities for cutting or welding and coagulating tissue. To combine the advantages of both wavelengths, we realized a multiwavelength laser system by simultaneously guiding erbium and holmium laser radiation by means of a single zirconium fluoride (ZrF(4)) fiber. Laser-induced channel formation in water and poly(acrylamide) gel was investigated by the use of a time-resolved flash-photography setup, while pressure transients were recorded simultaneously with a needle hydrophone. The shapes and depths of vapor channels produced in water and in a submerged gel after single erbium and after combination erbium-holmium radiation delivered by means of a 400-µm ZrF(4) fiber were measured. Transmission measurements were performed to determine the amount of pulse energy available for tissue ablation. The effects of laser wavelength and the delay time between pulses of different wavelengths on the photomechanical and photothermal responses of meniscal tissue were evaluated in vitro by the use of histology. It was observed that the use of a short (200-µs, 100-mJ) holmium laser pulse as a prepulse to generate a vapor bubble through which the ablating erbium laser pulse can be transmitted (delay time, 100 µs) increases the cutting depth in meniscus from 450 to 1120 µm as compared with the depth following a single erbium pulse. The results indicate that a combination of erbium and holmium laser radiation precisely and efficiently cuts tissue under water with 20-50-µm collateral tissue damage.

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.

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.

The adjacent thermal and mechanical tissue damage after normal-mode Ho:YAG (pulse length = 250 mus, lambda = 2.09 mum), Q-switched Ho:YAG (pulse length = 200 ns, lambda= 2.09 mum), and excimer (pulse length = 120 ns, lambda = 308 nm) pulsed laser irradiation of human thoracic aorta samples was studied in vitro. Surface temperatures were monitored during laser irradiation with an IR camera in air or a thermocouple in saline. Histological analysis of the irradiated sites was performed to assess thermal and mechanical damage to tissue surrounding the crater. The ablation of aortic tissue with any of the lasers resulted in a temperature buildup inside the tissue; this effect was most significant for the IR wavelength. Mechanical damage was observed in all cases but was most pronounced for the Q-switched Ho:YAG laser. Excimer ablation in air left behind a smooth surface; however, under saline the result was a much rougher surface.