An endoscopic approach providing near-infrared laser-induced coagulation with accurate depth limits.

This article investigates an endoscopic approach that utilizes negative pressure to achieve laser-induced thermal coagulation limited to the esophageal wall's mucosal and superficial submucosal layers. The study was built upon a series of studies combining numerical simulation based on the Monte-Carlo technique and ex vivo porcine tissue experiments, including apparatus design and histology analysis. An endoscopy apparatus was developed using 3D printing to validate the tissue stretching-based approach. A fiber-pigtailed diode was used as the near-infrared source, emitting 208.8 W/cm2 laser irradiance at 1.5 µm. Simulation results suggested that the approach successfully created a local heat well to prevent residual thermal effects (>65°C) from penetrating the deeper submucosal layer. Histology analysis of ex vivo tissues showed that at a fluence of 5.22 kJ/cm2, the depth of thermal coagulation was reduced by half compared to the control. With further preclinical studies, including endoscopy apparatus design, the approach can be applied to the larger esophageal surface.

Low frequency neuromuscular electrical stimulation applied to the bulbospongiosus muscle prolongs the ejaculation latency in a rat model.

Premature ejaculation (PE) is common, but its true pathophysiology is not clear, and treatments are limited. We aimed to investigate the effect of neuromuscular electrical stimulation applied in different modes and frequencies to the bulbospongiosus muscle on ejaculation parameters. In this study, 24 male Wistar albino rats were used. The rats were equally divided into three groups: control, high-frequency burst (HFB) and low-frequency (LF) (n = 8 each). Neuromuscular electrical stimulation was applied to the rats for 30 min. In the HFB group, this stimulation was applied in the burst mode at 80 Hz frequency using 200 microseconds (µs) transition time. In the LF group, manual stimulation was applied using a 2 Hz frequency and 200 µs transition time. Following the intraperitoneal administration of para-chloroamphetamine at a dose of 5 mg/kg, ejaculation time, increase in basal seminal vesicle pressure, seminal vesicle maximum pressure, number and interval time of seminal vesicle contractions and bulbospongiosus muscle electromyography activities were evaluated over 30 min. There was a significant difference between the groups in terms of ejaculation time (p = 0.002). The ejaculation times of the LF, HFB and control groups were 1344.71 ± 105.9, 908 ± 62 and 672 ± 149.7 s, respectively. The post hoc analysis revealed that the ejaculation time of the LF group was significantly longer than that of the HFB and control groups (p = 0.033 and p = 0.001, respectively). The remaining parameters did not differ significantly between the groups. The results showed that low-frequency (2 Hz) electrical stimulation applied to the male rats significantly prolonged the ejaculation time. It is thus considered that applying neuromuscular electrical stimulation before planned sexual activity can prevent the rhythmic contractions necessary for completing the ejaculatory process by maintaining subtetanic continuous contraction and prolonging the ejaculation time in patients with premature ejaculation complaints.

Guide mapping for effective superficial photothermal coagulation of the esophagus using computer simulations with ex vivo sheep model validation study.

OBJECTIVES: The transfer and widespread acceptance of laser-induced thermal therapy into gastroenterology remain a topic of interest. However, a practical approach to the quantitative effect of photothermal injury in the esophagus needs further investigation. Here, we aim to perform computer simulations that simulate laser scanning and calculate the laser-induced thermal damage area. The simulation engine offers the results in a guide map for laser coagulation with a well-confined therapeutic area according to laser irradiance and surface scanning speed. The study also presents validation experiments that include histology analyses in an ex vivo sheep esophagus model. METHODS: The simulation engine was developed based on the Monte-Carlo method and the Arrhenius damage integral. The computational model mimicked laser scanning by shifting the position of the calculated heat source in the grating system along the axis to be scanned. The performance of the simulations was tested in an ex vivo sheep esophagus model at a laser wavelength of 1505 nm. Histological analysis, hematoxylin-eosin staining, light microscope imaging, and block-face scanning electron microscopy were used to assess thermal damage to the tissue model. RESULTS: The developed simulation engine estimated the photothermal coagulation area for a surface scanning speed range of 0.5-8 mm/second and laser power of up to 0.5 W at a 0.9-nm laser diameter in a tissue model with a volume of 4 × 4 × 4 mm3 . For example, the optimum laser irradiation for effective photothermal coagulation in the mucosa and superficial submucosa depths was estimated to be between 16.4 and 31.8 W/cm2 , 23.2 and 38.1 W/cm2 at 0.5 and 1 mm/second, respectively. The computational results, summarized as a guide map, were directly compared with the results of ex vivo tissue experiments. In addition, it was pointed out that the comparative theoretical and experimental data overlap significantly in terms of energy density. CONCLUSIONS: Our results suggest that the developed simulation approach could be a seed algorithm for further preclinical and clinical trials and a complementary tool to the laser-induced photothermal coagulation technique for superficial treatments in the gastrointestinal tract. In future preclinical studies, it is thought that the simulation engine can be enriched by combining it with an in vivo model for different laser wavelengths.

Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model.

Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42°C with acute nerve damage observed above 46°C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation.

Superficial photothermal laser ablation of ex vivo sheep esophagus using a cone-shaped optical fiber tip.

Superficial photothermal laser ablation (SPLA) may be useful as a therapeutic approach producing a depth of injury that is sufficient to eliminate mucosal lesion but not deep enough to induce thermal effects in deeper tissue layers. The purpose of this preliminary study is twofold: (a) to describe design steps of a fiber probe capable of delivering a tightly focused laser beam, including Monte-Carlo-based simulations, and (b) to complete the initial testing of the probe in a sheep esophagus model, ex vivo. The cone-shaped (tapered) fiber tip was obtained by chemical etching of the optical fiber. A 1505 nm diode laser providing power up to 500 mW was operated in continuous wave. The successful SPLA of the sheep mucosa layer was demonstrated for various speed-power combinations, including 300 mW laser power at a surface scanning rate of 0.5 mm/s and 450 mW laser power at a surface scanning rate of 2.0 mm/s. Upon further development, this probe may be useful for endoscopic photothermal laser ablation of the mucosa layer using relatively low laser power.

High-speed optical coherence tomography by circular interferometric ranging.

Existing three-dimensional optical imaging methods excel in controlled environments but are difficult to deploy over large, irregular and dynamic fields. This has limited imaging in areas such as material inspection and medicine. To better address these applications, we developed methods in optical coherence tomography (OCT) to efficiently interrogate sparse scattering fields, i.e., those in which most locations (voxels) do not generate meaningful signal. Frequency comb sources are used to superimpose reflected signals from equispaced locations through optical subsampling. This results in circular ranging, and reduces the number of measurements required to interrogate large volumetric fields. As a result, signal acquisition barriers that have limited speed and field in OCT are avoided. With a new ultrafast, time-stretched frequency comb laser design operating with 7.6 MHz to 18.9 MHz repetition rates, we achieved imaging of multi-cm3 fields at up to 7.5 volumes per second.

Phase-stable Doppler OCT at 19 MHz using a stretched-pulse mode-locked laser.

We present a swept-wavelength optical coherence tomography (OCT) system with a 19 MHz laser source and electronic phase-locking of the source, acquisition clock, and beam scanning mirrors. The laser is based on stretched-pulse active mode-locking using an electro-optic modulator. Beam scanning in the fast axis uses a resonant micro-electromechanical systems (MEMS) -based mirror at ~23.8 kHz. Acquisition is performed at 1.78 Gigasamples per second using an external fixed clock. Phase sensitive imaging without need for k-clocking, A-line triggers, or phase-calibration methods is demonstrated. The system was used to demonstrate inter-frame and inter-volume Doppler imaging in the mouse ear and brain at 4D acquisition rates of 1, 30, 60 and 100 volumes/sec (V-scans/s). Angiography based on inter-frame and inter-volume methods are presented. The platform offers extremely fast and phase-stable measurements that can be used in preclinical angiographic and Doppler investigations of perfusion dynamics.

In-chip microstructures and photonic devices fabricated by nonlinear laser lithography deep inside silicon.

Silicon is an excellent material for microelectronics and integrated photonics1-3 with untapped potential for mid-IR optics4. Despite broad recognition of the importance of the third dimension5,6, current lithography methods do not allow fabrication of photonic devices and functional microelements directly inside silicon chips. Even relatively simple curved geometries cannot be realised with techniques like reactive ion etching. Embedded optical elements, like in glass7, electronic devices, and better electronic-photonic integration are lacking8. Here, we demonstrate laser-based fabrication of complex 3D structures deep inside silicon using 1 µm-sized dots and rod-like structures of adjustable length as basic building blocks. The laser-modified Si has a different optical index than unmodified parts, which enables numerous photonic devices. Optionally, these parts are chemically etched to produce desired 3D shapes. We exemplify a plethora of subsurface, i.e., "in-chip" microstructures for microfluidic cooling of chips, vias, MEMS, photovoltaic applications and photonic devices that match or surpass the corresponding state-of-the-art device performances.

Compensation of spectral and RF errors in swept-source OCT for high extinction complex demodulation.

We provide a framework for compensating errors within passive optical quadrature demodulation circuits used in swept-source optical coherence tomography (OCT). Quadrature demodulation allows for detection of both the real and imaginary components of an interference fringe, and this information separates signals from positive and negative depth spaces. To achieve a high extinction (∼60 dB) between these positive and negative signals, the demodulation error must be less than 0.1% in amplitude and phase. It is difficult to construct a system that achieves this low error across the wide spectral and RF bandwidths of high-speed swept-source systems. In a prior work, post-processing methods for removing residual spectral errors were described. Here, we identify the importance of a second class of errors originating in the RF domain, and present a comprehensive framework for compensating both spectral and RF errors. Using this framework, extinctions >60 dB are demonstrated. A stability analysis shows that calibration parameters associated with RF errors are accurate for many days, while those associated with spectral errors must be updated prior to each imaging session. Empirical procedures to derive both RF and spectral calibration parameters simultaneously and to update spectral calibration parameters are presented. These algorithms provide the basis for using passive optical quadrature demodulation circuits with high speed and wide-bandwidth swept-source OCT systems.

A rapid, dispersion-based wavelength-stepped and wavelength-swept laser for optical coherence tomography.

Optical-domain subsampling enables Fourier-domain OCT imaging at high-speeds and extended depth ranges while limiting the required acquisition bandwidth. To perform optical-domain subsampling, a wavelength-stepped rather than a wavelength-swept source is required. This preliminary study introduces a novel design for a rapid wavelength-stepped laser source that uses dispersive fibers in combination with a fast lithium-niobate modulator to achieve wavelength selection. A laser with 200 GHz wavelength-stepping and a sweep rate of 9 MHz over a 94 nm range at a center wavelength of 1550 nm is demonstrated. A reconfiguration of this source design to a continuous wavelength-swept light for conventional Fourier-domain OCT is also demonstrated.

Continuous-wave infrared subsurface optical stimulation of the rat prostate cavernous nerves using a 1490-nm diode laser.

OBJECTIVE: To optimize the infrared laser wavelength and optical nerve stimulation (ONS) parameters for both deep and rapid subsurface cavernous nerve (CN) stimulation in a rat model, in vivo. MATERIALS AND METHODS: A 150-mW, 1490-nm diode laser providing an optical penetration depth (OPD) of 518 µm in water was operated in continuous-wave mode during stimulation of the CNs in 8 rats for 15 seconds irradiation time through a custom-built, single-mode fiber optic probe capable of producing a collimated, 1-mm diameter laser beam. Successful ONS was judged by an intracavernous pressure response in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 nm and 1550 nm near-infrared diode laser wavelengths. RESULTS: Subsurface ONS of the rat CN was successful through fascia layers with a thickness up to 380 µm using an incident laser power of ∼50 mW. Intracavernous pressure response times as short as 4.6 ± 0.2 seconds were recorded using higher laser powers below the nerve damage threshold. CONCLUSION: The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper penetration than 1455-nm diode laser and more rapid and efficient nerve stimulation than 1550-nm diode laser.

Temperature-controlled optical stimulation of the rat prostate cavernous nerves.

Optical nerve stimulation (ONS) may be useful as a diagnostic tool for intraoperative identification and preservation of the prostate cavernous nerves (CN), responsible for erectile function, during prostate cancer surgery. Successful ONS requires elevating the nerve temperature to within a narrow range (~42 to 47°C) for nerve activation without thermal damage to the nerve. This preliminary study explores a prototype temperature-controlled optical nerve stimulation (TC-ONS) system for maintaining a constant (±1°C) nerve temperature during short-term ONS of the rat prostate CNs. A 150-mW, 1455-nm diode laser was operated in continuous-wave mode, with and without temperature control, during stimulation of the rat CNs for 15 to 30 s through a fiber optic probe with a 1-mm-diameter spot. A microcontroller opened and closed an in-line mechanical shutter in response to an infrared sensor, with a predetermined temperature set point. With TC-ONS, higher laser power settings were used to rapidly and safely elevate the CNs to a temperature necessary for a fast intracavernous pressure response, while also preventing excessive temperatures that would otherwise cause thermal damage to the nerve. With further development, TC-ONS may provide a rapid, stable, and safe method for intraoperative identification and preservation of the prostate CNs.

Subsurface near-infrared laser stimulation of the periprostatic cavernous nerves.

Successful identification and preservation of the cavernous nerves (CN), which are responsible for sexual function and vulnerable to damage during prostate cancer surgery, will require subsurface detection of the CN's beneath a thin fascia layer. This study explores the feasibility of optical nerve stimulation (ONS) in the rat with a fascia layer placed over the CN. Two near-infrared diode lasers with wavelengths of 1455 and 1550 nm were operated in continuous-wave mode for stimulation of the CN in 8 rats, in vivo. Successful ONS was confirmed by an intracavernous pressure (ICP) response in the rat penis at 1455 nm through fascia with a thickness up to 110 µm and at 1550 nm through fascia with a thickness up to 450 µm. Higher incident laser power was required to produce an ICP response as fascia thickness was increased. Also, weaker and slower ICP responses were observed as fascia thickness was increased. Subsurface ONS of the rat CN at a depth of 450 µm using a 1550 nm laser is feasible as an intermediate step towards developing ONS as an intra-operative diagnostic tool for identification and preservation of the cavernous nerves during prostate cancer surgery.

Continuous-wave laser stimulation of the rat prostate cavernous nerves using a compact and inexpensive all single mode optical fiber system.

BACKGROUND AND PURPOSE: Laser stimulation of the rat cavernous nerve (CN) recently has been demonstrated as an alternative to electrical stimulation for potential application in nerve mapping during nerve-sparing radical prostatectomy. Advantages include noncontact stimulation and improved spatial selectivity. Previous studies, however, have used large and/or expensive laser sources for stimulation. This study demonstrates the feasibility of optical stimulation of the rat CN, in vivo, using a compact, inexpensive all-single-mode fiberoptic system. MATERIALS AND METHODS: A 1455-nm wavelength infrared diode laser beam was coupled into a 9-µm-core single-mode fiber for delivery through a 10F laparoscopic probe and used for laser stimulation of the CN in a total of eight rats, in vivo. RESULTS: Laser stimulation of the CN was observed at threshold temperatures of 41°C, with intracavernous pressure response times as short as 4 s, and magnitudes up to 50 mm Hg, compared with baselines of 10 mm Hg. CONCLUSION: This novel, all-single-mode-fiber laser nerve stimulation system introduces several advantages including: (1) lower cost laser; (2) more robust fiberoptic design, eliminating alignment and cleaning of bulk optical components; and (3) improved Gaussian spatial beam profile for simplified alignment of the laser beam with the nerve. With further development, laser nerve stimulation may be useful for identification and preservation of the CN during prostate cancer surgery.

Continuous-wave infrared optical nerve stimulation for potential diagnostic applications.

Optical nerve stimulation using infrared laser radiation has recently been developed as a potential alternative to electrical nerve stimulation. However, recent studies have focused primarily on pulsed delivery of the laser radiation and at relatively low pulse rates. The objective of this study is to demonstrate faster optical stimulation of the prostate cavernous nerves using continuous-wave (cw) infrared laser radiation for potential diagnostic applications. A thulium fiber laser (λ=1870 nm) is used for noncontact optical stimulation of the rat prostate cavernous nerves in vivo. Optical nerve stimulation, as measured by an intracavernous pressure (ICP) response in the penis, is achieved with the laser operating in either cw mode, or with a 5-ms pulse duration at 10, 20, 30, 40, 50, and 100 Hz. Successful optical stimulation is observed to be primarily dependent on a threshold nerve temperature (42 to 45 °C), rather than an incident fluence, as previously reported. cw optical nerve stimulation provides a significantly faster ICP response time using a lower power (and also less expensive) laser than pulsed stimulation. cw optical nerve stimulation may therefore represent an alternative mode of stimulation for intraoperative diagnostic applications where a rapid response is critical, such as identification of the cavernous nerves during prostate cancer surgery.