Diffusing light modulated by focused ultrasound (FUS) or acousto optic (AO) sensing is a hybrid technique that utilizes ultrasound features, such as, deep penetration, localize and precise spatial resolution, to surpass optical scattering limitations in optical sensing and maintain the original optical contrast. In this paper, we compare the acousto-optic (AO) signal amplitude when using three different light sources; long coherence, laser diode (LD), and light emitting diode (LED). In recent years, there has been a growing trend towards the use of LEDs and laser diode LDs in optical applications because of their compact and small size, ease of use, safety features, and cost-effectiveness. Aim of this paper is to examine the capability of LDs and LEDs to be used in AO sensing. We evaluated differences in the tagging efficiency using detection of AO signal amplitude metrics. The results showed that particularly LDs are also capable of providing acceptable tagging efficiency in AO-based sensing compared with long coherent lasers and can be beneficial option for use in AO based techniques.
The multiwavelength focused ultrasound (FUS)-optic technique in development aims to provide application for spatially accurate measurements of tissue properties in the focus area in real-time. But setting up such a system is quite challenging due to several factors, for instance the integration of different optical sources, positioning of the optical and acoustic beams on the phantom, and synchronization. In this presentation, we present first steps towards designing a multiwavelength FUS-optic system that measures wavelength dependent changes in the focus area. As a test substance, we used intralipid solution, milk, and the mixture with different levels of concentration. The expected signal peak heights of tagged photons intensities of different wavelengths are partly dependent on the concentration due to the wavelength-dependent optical absorbance. Furthermore, detected FUS modulated amplitudes are in relation with the concentration of sample in focus area. The aim of this study is to characterize the relationship between FUS-optic signal peak heights and the different levels of sample concentration at different wavelengths.
Focusing Ultrasound (FUS) can be used to modulate diffusing light in tissue. In this method, diffused photons are modulated in the ultrasound focus area. Detecting these FUS modulated (or tagged) photons can provide spatially accurate information from the focus area. However, probably the biggest challenge in this method is to enable sufficient tagging photons since most of the illuminated and detected photons do not propagate thru the FUS target area resulting in a low number of tagged photons when compared to the background unmodulated light. Therefore, current applications utilizing such hybrid technique are still limited. Our study aims to optimize illumination and detection of photons that propagate through a FUS target area by adjusting the relative position and angle of a light source-detector pair. For the simulations, the K-wave toolbox was utilized to calculate the nonlinear acoustic pressure field in the discretized numerical model from the FUS source. Furthermore, light propagation in the model is simulated using an open-source Monte Carlo algorithm. The model design is a backward detection mode which is suitable for direct application to the human body.
Enhancing brain fluid movement across blood brain barrier (BBB) has been recognized as a potential treatment of neurodegenerative diseases. Moreover, BBB opening is of high interest also in brain drug delivery in the treatment of brain tumors/cancers. However, efficient therapies which are based on BBB opening are still limited because of insufficient understanding of mechanisms and safety issues. Currently, there are few promising methodologically diverse BBB opening approaches. In this paper, we use functional near-infrared spectroscopy (fNIRS) for the first time for monitoring cerebral hemoglobin and water concentration changes during BBB opening in mouse brain by using two different techniques: intra-arterial mannitol infusion (IAM) and focused ultrasound (FUS). Both of these BBB opening techniques are already in clinical use but their hemo- and hydrodynamic implications have not been investigated from comparative aspect. Two fibre detectors were attached on both sides of the mouse brain and the source fibre was attached on middle of forehead. Further, by using a combination of three wavelengths 690nm, 830nm and 980nm, that have sufficient light penetration in the mouse brain, we can show average dynamics of hemoglobin and water in the whole brain, synchronized with BBB opening. To validate the level of BBB opening we used Evans blue dye and show its accumulation in the brain parenchyma tissue with the corresponding fNIRS responses.
Photo-acoustic (PA) excitation was combined with skeletal quantitative ultrasound (QUS) for multi-mode ultrasonic assessment of human long bones. This approach permits tailoring of the ultrasonic excitation and detection so as to efficiently detect the fundamental flexural guided wave (FFGW) through a coating of soft tissue. FFGW is a clinically relevant indicator of cortical thickness. An OPO laser with tunable optical wavelength, was used to excite a photo-acoustic source in the shaft of a porcine femur. Ultrasonic signals were detected by a piezoelectric transducer, scanning along the long axis of the bone, 20-50 mm away from the source. Five femurs were measured without and with a soft coating. The coating was made of an aqueous gelatin-intralipid suspension that optically and acoustically mimicked real soft tissue. An even coating thickness was ensured by using a specific mold. The optical wave length of the source (1250 nm) was tuned to maximize the amplitude of FFGW excitation at 50 kHz frequency. The experimentally determined FFGW phase velocity in the uncoated samples was consistent with that of the fundamental antisymmetric Lamb mode (A0). Using appropriate signal processing, FFGW was also identified in the coated bone samples, this time with a phase velocity consistent with that theoretically predicted for the first mode of a fluid-solid bilayer waveguide (BL1). Our results suggest that photo-acoustic quantitative ultrasound enables assessment of the thickness-sensitive FFGW in bone through a layer of soft tissue. Photo-acoustic characterization of the cortical bone thickness may thus become possible.
A tunable pulsed laser with nano-second pulse duration is used to generate microbubbles in highly diluted nanoparticle
(Au, TiO2 and ZnO) suspensions. The microbubble explosion may produce shock wave which is in-phase detected by a
low-frequency piezoelectric transducer. The effects of particle size and category on the threshold laser fluence of shock
wave generation and the wave intensity are investigated. The interaction between laser and nanoparticles has significant
application in biomedicine such as photothermal diagnostic and therapy, as well as cosmetic or drug delivery in skin.
The laser photoacoustic spectroscopy (LPAS) can be applied analytically to determine the concentration of an analyte in
samples and its absorption variation as a function of time. The LPAS has advantages of higher detection sensitivity, pure
absorption measurement and much less interference by background scattering in comparison with traditional optical
spectroscopy. On the other hand, the apparatus is simpler and more generally useful than that of fluorescent
spectroscopy. In this study, we built a photoacoustic setup of a Q-switched Nd:YAG laser excited at the third harmonic
wavelength and a wideband piezoelectric transducer clamped to the side of a cuvette. The samples included NADH
solutions, mitochondrial suspensions and Intralipid-ink mixtures. The experiment results show that the lowest detectable
absorption of the setup is in the order of 10-5 cm-1; the detectable concentration of NADH in a buffer is as low as 1.67
μM. When monitoring mitochondrial suspensions, the minimal concentration that can be detected is lower than 0.1
mg/mL and the absorption variation caused by full reduction of NAD+ to NADH in mitochondria can be detected.
This study involves measurements of pulp consistency in cuvette and by an online apparatus, by innovatively scattering photoacoustic (SPA) method. The theoretical aspects were described at first. Then, a few kinds of wood fiber suspensions with consistencies from 0.5% to 5% were studied in cuvette. After that, a pilot of online apparatus was built to measure suspensions with fiber consistency lower than 1% and filler content up to 3%. The results showed that although there were many fiber flocks in cuvette which strongly affected the measurement accuracy of samples consistencies, the apparatus can sense fiber types with different optical and acoustic properties. The measurement accuracy can be greatly improved in the online style apparatus, by pumping suspension fluids in a circulating system to improve the suspension homogeneity. The results demonstrated that wood fibers cause larger attenuation of acoustic waves but fillers do not. On the other hand, fillers cause stronger scattering of incident light. Therefore, our SPA apparatus has a potential ability to simultaneously determine fiber and filler fractions in pulp suspensions with consistency up to 5%.
Conventional photoacoustic techniques in composition determination and biomedical diagnose and imaging are
based on the optical absorption in target substance or objects from which the photons to be scattered are not
concerned. It is obvious that the intensities of scattered lights closely relate to the property of the interrogated
substance, therefore measuring the signals produced by them can give rise to more information of the substance.
Based on this idea, a novel method entitled scattering photoacoustic (SPA) method is put forward to study weak
absorption suspensions with highly scattering. In this method, a near infrared pulse laser irradiates the studied object
which contacts with external absorbers, resulting the generation of a few photoacoustic signals; one is produced in
the studied object as conventional case, others are in external absorbers which are produced by the scattered photons.
All these signals are successively received by a piezoelectric detector with short damping period. Analyzing these
signals is capable of determining reduced scattered coefficient and absorption coefficient, as well as acoustic
attenuation of studied suspensions. Some measurement results in intralipid and fibre (paper pulp) suspensions are
given rise to in the end.
Laser photoacoustics (PA) and optical coherence tomography (OCT) are versatile and sensitive techniques for
biomedical diagnostics, imaging, and measurements. In this paper, the fundamentals of PA and OCT are considered and
the applications in biomedicine reviewed. The properties of the two techniques are compared to find the proper technique
for a specific application. The problems and restrictions, dependent on the factors of the human body, which have to be
reduced before the clinical utilization of the techniques, are pointed out. The PA technique is more suitable for measuring
or imaging the objects located in deep tissue or organs and for sensing the physiological changes caused by compositions
with larger absorption variation, such as hemoglobin, blood oxygenation, and melanin. OCT is more suitable for imaging
tissue surface and subsurface structures and fine structures and for sensing the physiological changes caused by
compositions with larger scattering and refractive index variation, such as skin water, tissue glucose, and sweat.
The size distribution and total amount of the particles in paper pulp is vital information for the paper manufacturer in optimising process control and maintaining a high product quality. There is a further need for improving the on-line measurement methods to measure these parameters. It is known that fibre and fines fractions in the pulp have different optical and acoustic properties. In this study, we simultaneously use laser radar and laser generation of acoustic waves to further study optical and acoustic parameters, such as optical time delay, acoustic speed and attenuation. A near infrared pulse laser is used to illuminate the pulp suspensions and the time-of-flight of scattering photons is recorded; and at the same time, a high energy pulsed laser is applied to produce an acoustic wave. The acoustic wave propagates through the pulp suspensions and an acoustic transducer is used to detect the signals from which the attenuation and acoustic speed are determined. The results show that these combined optical techniques can potentially determine the content of fibres and fine particles simultaneously.
In this paper, optical measurement techniques, which enable non-invasive measurement, are superimposed to glucose sensing in scattering media. Used measurement techniques are Optical Coherence Tomography (OCT), Photoacoustic spectroscopy (PAS) and laser pulse Time-of-Flight (TOF) measurement using a streak camera. In parallel with measurements, a Monte-Carlo (MC) simulation models have been developed. Experimental in vitro measurements were performed using Intralipid fat emulsion as a tissue simulating phantom for OCT and TOF measurements. In PAS measurements, a pork meat was used as a subject but also preliminary in vivo measurements were done. OCT measurement results show that the slope of the OCT signal's envelope changes as a function of glucose content in the scattering media. TOF measurements show that the laser pulse full width of half maximum (FWHM) changes a little as function of glucose content. An agreement with MC-simulations and measurements with Intralipid was also found. Measurement results of PAS technique show that changes in glucose content in the pork meat tissue can be measured. In vivo measurements with a human volunteer show that other factors such as physiological change, blood circulation and body temperature drift may interfere the PA response of glucose.
Peculiarities of light transport in IntralipidTM solutions and the effect of glucose on light scattering properties of the
solution at two different IntralipidTM concentrations were studied with optical coherence tomography (OCT) technique
in vitro. An open air OCT system using a superluminescent light source with center wavelength = 830 nm was used. 5% IntralipidTM
solutions were used to simulate a biological tissue (skin) in our experiment. Glucose concentrations at the
physiologically relevant level were added to IntralipidTM solutions. Increasing IntralipidTM concentration increases the scattering coefficient of the media meanwhile increasing glucose concentration increases the refractive index of the
media and reduces the scattering coefficient of the media. The experimental data were compared to Monte Carlo
simulations. We also made the simulations for 2% IntralipidTM solution. The results indicate that glucose added to 2 and 5% IntralipidTM solutions changes their scattering properties, which is manifested by a decrease in the slope of the OCT signal. This finding shows the ways of using OCT for sensing glucose and monitoring the alterations of its content in
biotissues. Some discrepancies between measurements and simulations were found, which need further investigation.
Non-invasive blood glucose determination has been investigated by more than 100 research groups in the world during the past fifteen years. The commonly optical methods are based on the capacity of near-IR light to penetrate a few hundreds micrometers or a few millimeters into human tissue where it interacts with glucose. A change of glucose concentration may modify the optical parameters in tissue, with the result that its glucose concentration can be extracted by analyzing the received optical signals. This paper demonstrates that glucose affects on the scattering coefficient of human blood, by applying the streak camera and pulsed photoacoustic techniques; and drinking water seems also affecting on PA signal from skin surface.
The near-infrared photoacoustic technique is recognized as a potential method for the non-invasive determination of human glucose, because near-infrared light can incident a few millimeters into human tissue, where it produces an acoustic wave capable of carrying information about the composition of the tissue. This paper demonstrates a photoacoustic glucose measurement in a blood sample as a step toward a non-invasive measurement. The experimental apparatus consists of a near-infrared laser diode operating with 4 micro joules pulse energy at 905 nm, a roller pump connected to a silicon plastic tube and a cuvette for circulating the blood sample. In addition, the apparatus comprises a PZT piezoelectric transducer integrated with a battery-powered preamplifier to receive the photoacoustic signal. During the experiment, a glucose solution is mixed into a human blood sample to change its concentration. Although the absorption coefficient of glucose is much smaller than that of blood in the near-infrared region, the osmotic and hydrophilic properties of glucose decrease the reduced scattering coefficient of blood caused by the dissolved glucose surrounding the blood cells. This changes the distribution of the absorbed optical energy in blood, which, in turn, produces a change in the photoacoustic signal. Our experiment demonstrates that signal amplitudes in fresh and stored blood samples in crease about 7% and 10%, respectively, when the glucose concentration reaches the upper limit of the physiological region (500 mg/dl).
The photoacoustic technique (laser-induced acoustic waves), which is less affected by light scattering than the optical method, is based on optical absorption and the heat properties of illuminated media. Although photoacoustic techniques have been used to study tissues, only a few authors discuss the laser- induced photoacoustic source u the acoustic transmitter. This paper employs the Monte Carlo method to simulate a laser-induced acoustic transmitter in a two-layered tissue model. The shape and location of the transmitter is dependent not only on the optical parameters and heat properties of the tissue, but also on the diameter of the laser beam. A thin beam produces a cylindrical transmitter in a shallow layer of the tissue, whereas a sturdy beam tends to generate a plate-like transmitter and drive it deeply into the tissue. Studying the properties of the transmitter may provide useful insights in several respects: it may facilitate the reception of the acoustic signal, the measuring of the distribution of optical parameters, and the determination of layer thickness and the inner structure of tissues. The results of this paper also indicate that although a thin laser beam can produce a high transverse resolution in photoacoustic imaging, there may be a trade-off in imaging depth.
A NIR laser diode photoacoustic sensor is designed and used in tissue measurement. Laser diode is easy to carry out portable sensor. Because of low absorption of tissue in NIR region and the limited output power of the diode, the gain and SNR of the receiver should be high for measuring very low level signals. Developing higher pulse energy of laser diode and more sensitive transducer are the key for the diode sensor in application of biomedical measurement.
The so-called photoacoustic technique combines optical properties, such as absorption and scattering, with acoustic properties, such as sound velocity and absorption, to monitor and measure the physical properties of materials. This paper comprises a theoretical study on the properties of acoustic pulses and a discussion on earlier theories presented in literature. It also describes and analyzes the results of simulation tests based on the Monte-Carlo method, undertaken to examine the effects that absorption and scattering co-efficients of two-layer media have on the shape of the acoustic transmitter. Finally, the theoretical results are corroborated with measurements using a CO2 laser and a two-wavelength diode laser PA system, developed during the study.
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