In vivo endoscopic ultrasound imaging with a rotational-scanning, all-optical ultrasound probe.

All-optical ultrasound manipulates ultrasound waves based on laser and photonics technologies, providing an alternative approach for pulse-echo ultrasound imaging. However, its endoscopic imaging capability is limited ex vivo by the multifiber connection between the endoscopic probe and the console. Here, we report on all-optical ultrasound for in vivo endoscopic imaging using a rotational-scanning probe that relies on a small laser sensor to detect echo ultrasound waves. The acoustically induced lasing frequency change is measured via heterodyne detection by beating the two orthogonally polarized laser modes, enabling a stable output of ultrasonic responses and immunity to low-frequency thermal and mechanical disturbances. We miniaturize its optical driving and signal interrogation unit and synchronously rotate it with the imaging probe. This specialized design leaves a single-fiber connection to the proximal end and allows fast rotational scanning of the probe. As a result, we used a flexible, miniature all-optical ultrasound probe for in vivo rectal imaging with a B-scan rate of 1 Hz and a pullback range of ∼7 cm. This can visualize the gastrointestinal and extraluminal structures of a small animal. This imaging modality offers an imaging depth of 2 cm at a central frequency of ∼20 MHz, showing promise for high-frequency ultrasound imaging applications in gastroenterology and cardiology.

Butyrate prevents the migration and invasion, and aerobic glycolysis in gastric cancer via inhibiting Wnt/ß-catenin/c-Myc signaling.

Gastric cancer (GC) remains a common cause of cancer death worldwide. Evidence has found that butyrate exhibited antitumor effects on GC cells. However, the mechanism by which butyrate regulate GC cell proliferation, migration, invasion, and aerobic glycolysis remains largely unknown. The proliferation, migration, and invasion of GC cells were tested by EdU staining, transwell assays. Additionally, protein expressions were determined by western blot assay. Next, glucose uptake, lactate production, and cellular ATP levels in GC cells were detected. Furthermore, the antitumor effects of butyrate in tumor-bearing nude mice were evaluated. We found, butyrate significantly prevented GC cell proliferation, migration, and invasion (p < .01). Additionally, butyrate markedly inhibited GC cell aerobic glycolysis, as shown by the reduced expressions of GLUT1, HK2, and LDHA (p < .01). Moreover, butyrate notably decreased nuclear ß-catenin and c-Myc levels in GC cells (p < .01). Remarkably, through activating Wnt/ß-catenin signaling with LiCl, the inhibitory effects of butyrate on the growth and aerobic glycolysis of GC cells were diminished (p < .01). Moreover, butyrate notably suppressed tumor volume and weight in GC cell xenograft nude mice in vivo (p < .01). Meanwhile, butyrate obviously reduced nuclear ß-catenin, c-Myc, GLUT1, HK2 and LDHA levels in tumor tissues in GC cell xenograft mice (p < .01). Collectively, butyrate could suppress the growth and aerobic glycolysis of GC cells in vitro and in vivo via downregulating wnt/ß-catenin/c-Myc signaling. These findings are likely to prove useful in better understanding the role of butyrate in GC.

Compact polarimetric heterodyning DBR fiber laser sensor with high temperature resistance.

We report on a short-cavity polarization beat-frequency distributed Bragg reflector (DBR) fiber laser that can operate in an unprecedentedly wide range of temperatures from -200∘ C to 500°C. The beat-frequency signal inherited by the intrinsic fiber birefringence enables implementation of the laser as an eligible temperature or hydrostatic pressure sensor. Furthermore, type-IIa Bragg reflectors allow the annealing of high temperature on the laser cavity to suppress the phase noise of the lasing signal effectively. This research will guide future attempts to achieve high-precision sensing and high-performance signal generation using polarized beat-frequency DBR fiber lasers in harsh environments.

Photoacoustic computed tomography by using a multi-angle scanning fiber-laser ultrasound sensor.

Photoacoustic computed tomography (PACT) can ultrasonically image optical absorbers in biological tissues by using a linear piezoelectric transducer array, but some features can not be visualized as a result of the limited acceptance angle. The optical ultrasound sensors for photoacoustic imaging have received great interests, because of their compact sizes, comparable sensitivities to their electric counterparts, as well as the extended field/angle-of-view. In this work, we have developed a PACT system based on a fiber-laser based ultrasound sensor. Two-dimensional imaging was performed by horizontally scanning the sensor and image reconstruction via back projection, and three-dimensional imaging was further achieved by repeating such scanning process at multiple angles, based on inverse Radon transform. The axial and lateral resolutions are 93 and 220 µm in three-dimensional imaging. The fiber-based PACT can resolve more features than that with a piezoelectric transducer array, taking advantage of the dual-60-degree vision angles of the sensor.

Acoustic-spectrum-compensated photoacoustic microscopy.

Photoacoustic microscopy (PAM) can label-free image oxy- and deoxy-hemoglobin (${{\rm HbO}_2}$HbO2 and Hb) concentrations in vivo, providing useful information for metabolic researches and diagnostic applications. Conventional PAM assumes a linear relationship between the photoacoustic amplitude and the absorption coefficient. However, many factors, including absorber size, laser pulse width, and frequency response of the ultrasound transducer, may affect the measured acoustic spectrum and the shape of the temporal photoacoustic signal. The ultrasound transducer may weigh the blood vessels differently according to their diameters. In addition, the pulse width also affects the photoacoustic signal amplitude. These factors may cause inaccurate measurement of Hb and ${{\rm HbO}_2}$HbO2 concentrations. To address this issue, we develop an acoustic-spectrum-compensated optical-resolution PAM (OR-PAM) that corrects the nonuniform acoustic spectrum and makes the quantitative results to be independent of the vessel diameter and pulse width. In dual-wavelength OR-PAM, we demonstrate that the acoustic spectrum compensation can improve the accuracy of oxygen saturation imaging by $\sim{15}\% $∼15%.

Dual-Polarized Fiber Laser Sensor for Photoacoustic Microscopy.

Optical resolution photoacoustic microscopy (OR-PAM) provides high-resolution, label-free and non-invasive functional imaging for broad biomedical applications. Dual-polarized fiber laser sensors have high sensitivity, low noise, a miniature size, and excellent stability; thus, they have been used in acoustic detection in OR-PAM. Here, we review recent progress in fiber-laser-based ultrasound sensors for photoacoustic microscopy, especially the dual-polarized fiber laser sensor with high sensitivity. The principle, characterization and sensitivity optimization of this type of sensor are presented. In vivo experiments demonstrate its excellent performance in the detection of photoacoustic (PA) signals in OR-PAM. This review summarizes representative applications of fiber laser sensors in OR-PAM and discusses their further improvements.

Dual-color distributed Bragg reflector fiber laser with simultaneous emission at 1.06 µm and 1.55 µm wavebands.

A dual-wavelength fiber laser is proposed by the use of Er/Yb co-doped active fiber and a pair of novel Bragg-grating reflectors. The Bragg grating presents strong reflections of both third and second harmonics in accordance with the gain of ytterbium and erbium ion, respectively, enabling the laser emitted at 1.06 µm and 1.55 µm wavebands simultaneously with a short linear cavity structure. Adjusting reflectivity of the harmonics in the grating can influence the intensity contrast of the two lasing signals. Optimization on the compactness and brightness of the laser is achieved by adapting the harmonic wavelengths with the optimal gain windows of the ytterbium and erbium ions.

Sensitivity characteristics of broadband fiber-laser-based ultrasound sensors for photoacoustic microscopy.

High-frequency fiber laser sensor is a new acoustic detector for photoacoustic imaging. However, its performance has not been thoroughly studied. Here, we present a comprehensive characterization of a fiber laser sensor for photoacoustic imaging. Ultrasound waves deform the fiber laser cavity and induce frequency changes in the heterodyning output signal. The sensitivity peaks at 22 MHz, which is associated with an azimuthal mode number l = 2 and a radial mode number n = 1. The broadband acoustic sensitivity in terms of frequency shift is 2.25 MHz/kPa and the noise-equivalent pressure reaches 45 Pa with a sampling rate of 100 MHz. The 3-dB bandwidth is 18 MHz for spherical-wave detection. We characterized the spatial distribution of acoustic sensitivity. The sensitivity along the fiber longitudinal direction varies with the laser spatial mode and is determined by the grating and cavity parameters. The sensitivity at the azimuthal direction presents a |cos(2θ)| dependence as a result of fiber core asymmetry. In the radial direction, the sensitivity is inversely proportional to the square root of the distance between the source and the detector. The acoustic sensitivity can be enhanced by reducing the cavity length. We experimentally show that a short sensor can enhance the contrast and penetration depth of PAM than a long one.

2 MHz multi-wavelength pulsed laser for functional photoacoustic microscopy.

Fast functional photoacoustic microscopy requires multi-wavelength pulsed laser sources with high pulse repetition rates, short wavelength switching time, and sufficient pulse energies. Here, we report the development of a stimulated-Raman-scattering-based multi-wavelength pulsed laser source for fast functional photoacoustic imaging. The new laser source is pumped with a 532 nm 1 MHz pulsed laser. The 532 nm laser beam is split into two: one pumps a 5 m optical fiber to excite a 558 nm wavelength via stimulated Raman scattering; the other goes through a 50 m optical fiber to delay the 532 nm pulse by 220 ns. The two beams are combined and coupled into an optical fiber for photoacoustic excitation. As a result, the new laser source can generate 2 million pulses per second, switch wavelengths in 220 ns, and provide hundreds of nanojoules pulse energy for each wavelength. Using this laser source, we demonstrate optical-resolution photoacoustic imaging of microvascular structures and oxygen saturation in the mouse ear. The ultrashort wavelength switching time enables oxygen saturation imaging of flowing red blood cells, which is valuable for high-resolution functional imaging.

Response of an erbium-doped dual-polarization fiber laser to a perpendicular gradient magnetic field.

Direct interaction between fiber lasers and a magnetic field is useful but seldom explored because fiber is known as magnetic field insensitive. In this Letter, the response of an erbium-doped dual-polarization fiber laser to a perpendicular gradient magnetic field is investigated. Measured as beat note frequency change, significant response greater than 500 MHz has been observed that is within theoretical expectation, and translates to a birefringence change of about 4×10-6 and a potentially very high response to a magnetic field of about 12.8 pT/Hz. The response can be further enhanced by increasing the gradient of the gradient magnetic field.

Corrugated-Diaphragm Based Fiber Laser Hydrophone with Sub-100 µPa/Hz1/2 Resolution.

In this work, a beat-frequency encoded fiber laser hydrophone is developed for high-resolution acoustic detection by using an elastic corrugated diaphragm. The diaphragm is center-supported by the fiber. Incident acoustic waves deform the diaphragm and induce a concentrated lateral load on the laser cavity. The acoustically induced perturbation changes local optical phases and frequency-modulates the radio-frequency beat signal between two orthogonal lasing modes of the cavity. Theoretical analysis reveals that a higher corrugation-depth/thickness ratio or larger diaphragm area can provide higher transduction efficiency. The experimentally achieved average sensitivity in beat-frequency variation is 185.7 kHz/Pa over a bandwidth of 1 kHz. The detection capability can be enhanced by shortening the cavity length to enhance the signal-to-noise ratio. The minimum detectable acoustic pressure reaches 74 µPa/Hz1/2 at 1 kHz, which is comparable to the zeroth order sea noise.

Study of lateral-drilled DBR fiber laser and its responsivity to external refractive index.

We report a lateral-drilled DBR fiber laser which contains a defective parabola-like opening inside the cavity fabricated by the CO2-laser exposure and study the laser responsivity to external refractive index (RI). Surrounding materials can readily reach the vicinity of the fiber core via the opening and interact with the laser mode. Research shows that the laser emission power mainly relies on changes of external RI while the lasing wavelength on temperature. The effects of structural parameters, pump power, and external refractive index on the RI responsivity of the device are demonstrated. The lasing threshold condition is also concerned. This work provides an opportunity for controlling emission characteristics of the DBR fiber laser through modification of external RI value, of which the results are valuable for the potential applications in optical sensing, tunable lasing, and etc.

Highly sensitive fiber laser ultrasound hydrophones for sensing and imaging applications.

We have developed highly sensitive photonic ultrasound hydrophones based on polymer-packaged dual-polarization-mode fiber lasers. The incident ultrasound wave is scattered by the polymer cylinder due to the difference in elastic property. The scattered wave can drive harmonic vibration of the cylinder and result in optical response in terms of beat-frequency variation of the laser output. Experimental results exhibit a broadband ultrasound response at frequencies below 1 MHz. The individual vibration modes are excited by the ultrasound waves with different efficiencies, yielding a frequency-dependent response. A hydrophone with a diameter of 5 mm presents a detection limit of 2 mPa/Hz1/2 at 200 kHz. We further demonstrate its capability of ultrasound imaging for applications in underwater acoustics and sonar systems.

Highly sensitive fiber laser ultrasound hydrophones for sensing and imaging applications: publisher's note.

This note corrects the range of acoustic frequencies mentioned in the opening paragraph of Opt. Lett.41, 4530 (2016)OPLEDP0146-959210.1364/OL.41.004530 as having rarely been investigated.

Thermally triggered fiber lasers based on secondary-type-In Bragg gratings.

The secondary-type-In grating formed in a small-core photosensitivity active fiber is discovered and investigated. Due to the different grating types, the transmission dip of a secondary grating structure chases and integrates with the type-In grating structure as the temperature increases, which strengthens the reflectivity of the grating. By use of these secondary-type-In gratings as Bragg reflectors, a thermally activated distributed Bragg reflector (DBR) fiber laser is proposed, which can be potentially used in high-temperature alarms and sensors.

Type IIa Bragg grating based ultra-short DBR fiber laser with high temperature resistance.

We report on the fabrication of a thermally resistant ultra-short distributed Bragg reflector (DBR) fiber laser based on the photo inscription of two wavelength-matched type IIa gratings in a thin-core Er-doped fiber. With continuous UV exposure, each Bragg reflector initially grows as a type I grating, followed by decay in strength, and then re-grows as a type IIa grating with enhanced thermal resistance. The DBR laser, with an entire length of 13 mm, can stably operate at 600°C with single longitude mode, which provides potential applications in high temperature environments.

Implementation of a widely tunable microwave signal generator based on dual-polarization fiber grating laser.

In this paper, we demonstrate the implementation of a widely tunable microwave signal generator based on a dual-polarization fiber grating laser. The laser contains two strong, wavelength-matched Bragg gratings photoinscribed in an Er-doped fiber and emits two polarization modes when pumped with a 980 nm laser diode. By beating the two modes, a microwave signal with a signal-to-noise ratio over 60 dB can be obtained. For a free running laser the fluctuations in intensity and frequency of the microwave signal are ±1 dB and ±5 kHz, respectively, and the noise level is about -40 dBc/Hz at 1 kHz. The frequency can be continuously tuned from 1.8 to 15.1 GHz, by transversely loading the laser cavity and changing the intracavity birefringence by use of a piezoelectric transducer-based mechanical device. The measured response time rate of tuning is about 90 MHz/µs and the intensity fluctuation at different frequencies is less than ±1.5 dB. The frequency fluctuation under loading is controlled within 1 MHz by introducing an electrical feedback.

Stabilization of microwave signal generated by a dual-polarization DBR fiber laser via optical feedback.

Microwave signals can be generated by beating the two orthogonal polarization modes from a dual-frequency fiber grating laser. In this paper, we present that the phase noise of the microwave signal can be significantly reduced via optical feedback by cascading an external cavity. This is achieved as a result of the bandwidth narrowing of each polarization laser mode when introducing phase-matched feedbacks into the laser cavity. By optimizing the external cavity length and the feedback ratio, the noise level over low frequencies has been reduced by up to 30 dB, from -42 to -72 dBc/Hz at 1 kHz, and from -72 to -102 dBc/Hz at 10 kHz. Meanwhile the relaxation resonant peaks can be eliminated. Compared with the existing techniques, the present method can offer a cost-effective, low-noise microwave signal, without the requirement for complex electrical feedback system.

Health Interventions May Have Divergent Impacts on Health and Economic Equity: A Case Study of the Community-Based Hypertension Improvement Project in Ghana.

BACKGROUND AND OBJECTIVE: Improving health and economic equity are key objectives in priority setting, particularly in low-income and middle-income countries. This study aims to assess the distributional impacts of the Community-based Hypertension Improvement Project (ComHIP) on health and economic outcomes across wealth quintiles in Ghana. METHODS: We developed a decision analytical model to simulate a 30 million cohort of Ghanaians aged 15-49 years. The study specified health outcomes as the prevention of stroke cases and averting deaths among those with hypertension. Furthermore, we explored economic impacts, including savings in out-of-pocket costs for stroke patients and government spending. Financial risk protection against catastrophic and impoverishing health expenditures was also examined. We assessed these outcomes across wealth quintiles, and the corresponding concentration indexes (CIXs) were determined. RESULTS: It was estimated that ComHIP could prevent 1450 stroke cases and 564 related deaths annually. Health benefits were observed to be more significant among the wealthier quintiles (CIX 0.217), mainly attributed to a higher occurrence of hypertension within these groups. ComHIP was also projected to result in an annual saving of USD 49,885 in individuals' out-of-pocket costs (CIX 0.262) and USD 37,578 in government spending (CIX 0.146). These savings correspond to the prevention of 335 catastrophic health expenditure cases (CIX - 0.239) and 11 impoverishing health expenditure cases (CIX - 0.600). CONCLUSIONS: While ComHIP provides greater health benefits to wealthier groups, it offers substantial financial risk protection for the less wealthy. This study highlights the importance of considering equity in both health and financial risk when making priority-setting decisions.