Photoacoustic (PA) tomography can be useful to measure the hemoglobin concentration in blood vessels and tissues, and provide important information to determine the course of treatment for hypoxic malignant cancer which possesses the resistance to treatment. To image the hemoglobin concentration and oxygen saturation, the reconstruction of absorption coefficients at multiple wavelengths is required to correct the penetration depths of the multiple wavelengths of light. In this study, the authors tried the image reconstruction of the absorption coefficient for various concentration of photon absorber. Additionally, the effects of the regularizations minimizing 1-norm and p-norm (0<p<1) were compared to examine the improvement of the spatial resolution limited by the characteristics and configurations of the ultrasound transducer and illumination. The PA pressure waves were measured by the probe consisted of the optical fiber and the focused ultrasound transducer. The absorption coefficients of the tubes containing black ink in the phantom made of aqueous solution of Intralipid were from 0.2 to 1.0 mm-1 at a wavelength of 755 nm, corresponding to the range from normoxic to hypoxic condition of the whole blood. Although the tubes with various absorption coefficients were reconstructed with 1-norm regularization, the tube was reconstructed broadly. On the other hand, the regularization technique minimizing p-norm (0<p<1) localized the tube better than 1-norm regularization. The regularization minimizing p-norm (0<p<1) will improve the spatial resolution of the PA tomography.
By reconstructing the optical properties such as the absorption coefficient, quantitative photoacoustic tomography (QPAT) images the micro blood vessels and the hemoglobin concentration quantitatively. QPAT is accomplished by solving the inverse problem of the photoacoustic (PA) measurement based on the phenomena of the light and PA pressure wave propagation. The light propagation is described by the radiative transfer equation, which is approximately calculated with the Monte Carlo (MC) simulation. The propagation of the PA pressure wave is described by the PA wave equation. The authors have been studying the QPAT image reconstruction algorithm using MC simulation and linearization. Near-infrared light with a wavelength of 755 nm that penetrates deep inside the biological medium was used. The absorption coefficient was reconstructed from the PA signals measured by the probe, which was the combination of the optical fiber and the focused ultrasound transducer consisting of P(VDF-TrFE) piezo electric film. The QPAT image with 10-mm depth was reconstructed in the numerical and phantom experiments. Pursuing more realistic situation of the micro vessel imaging, we conducted animal experiment to validate the QPAT image reconstruction. In the animal experiments, we tried to image the blood vessels of rabbit’s ear. The rabbit ear was placed under the tissue-mimicking scattering layer. Through the numerical, phantom, and animal experiments, the instrumental and computational conditions for QPAT for pathological imaging will be investigated by comparing the QPAT images of the phantom and animal.
Visualization of small tumors inside biological tissue is important in cancer treatment because that promotes accurate surgical resection and enables therapeutic effect monitoring. For sensitive detection of tumor, we have been developing photoacoustic (PA) imaging technique to visualize tumor-specific contrast agents, and have already succeeded to image a subcutaneous tumor of a mouse using the contrast agents. To image tumors inside biological tissues, extension of imaging depth and improvement of sensitivity were required. In this study, to extend imaging depth, we developed a PA tomography (PAT) system that can image entire cross section of mice. To improve sensitivity, we discussed the use of the P(VDF-TrFE) linear array acoustic sensor that can detect PA signals with wide ranges of frequencies. Because PA signals produced from low absorbance optical absorbers shifts to low frequency, we hypothesized that the detection of low frequency PA signals improves sensitivity to low absorbance optical absorbers. We developed a PAT system with both a PZT linear array acoustic sensor and the P(VDF-TrFE) sensor, and performed experiment using tissue-mimicking phantoms to evaluate lower detection limits of absorbance. As a result, PAT images calculated from low frequency components of PA signals detected by the P(VDF-TrFE) sensor could visualize optical absorbers with lower absorbance.
We proposed a method of quantifying the effective attenuation coefficients of optical absorbers which uses the continuous wavelet transform to calculate the time-resolved frequency spectra of photoacoustic (PA) signals. In order to apply the method to blood oxygenation monitoring of blood vessels, this study discusses how to reduce the effects of blood vessel diameters, which influences on the time resolved frequency spectra of PA signals. Numerical simulations which calculate the PA signals produced from blood vessel phantoms with various diameters were performed. The simulations revealed that the frequency of PA signal became independent from the vessel diameters by measuring the PA signal from small area. The frequencies of simulated PA signals were proportional to the effective attenuation coefficients with a correlation coefficient of 0.99, and a slope of 0.035 MHz/cm-1 under condition that the measurement area was 4.0 mm at a frequency of 1.5 MHz. Thus we used the focused acoustic sensor of which focusing the foregoing measurement area. It consisted of a P(VDF-TrFE) film, which was characterized by broad frequency band. As results of experiments using the focused acoustic sensor, the frequencies of PA signals produced from blood vessel phantoms were proportional to the effective attenuation coefficients with correlation coefficient of 0.96 although the frequencies were suffered from deviations of 0.135 MHz, which corresponded to the effective attenuation coefficient of 3.46 cm-1. Since the large deviations were caused by experimental factors such as sensor alignment, it is required to improve robustness to the experimental factors.
Quantification of the optical absorption coefficients of optical absorbers using photoacoustic (PA) pressure waves with
broadband frequency was reported. We proposed to use continuous wavelet-transform (CWT) to obtain time-resolved
frequency spectra of PA signals and demonstrated the relationship between optical absorption coefficients of optical
absorbers and CWT of PA signals. However, the optical absorption coefficients of the optical absorbers were not
quantified. Thus, in this research, we quantified optical absorption coefficients of optical absorbers by using the
calibration curve which relates the optical absorption coefficients of optical absorbers and CWTs of PA signals. The
calibration curve is derived from the simulation. However, due to the frequency response of the acoustic sensor, the
simulated PA pressure waves differed from the measured PA signals. Thus, we measured the frequency response of the
acoustic sensor. By convolving the frequency response of the acoustic sensor to the simulated pressure waves, we
simulated the PA signals which were obtained by measuring the PA pressure wave using the acoustic sensor. The
calibration curve derived from the simulated PA signal enabled to quantify optical absorption coefficients of optical
absorbers. We verified the method by quantifying optical absorption coefficients of blood vessel phantoms which is
tubes filled with diluted inks with optical absorption coefficients from 10 to 40 cm-1. As results, the simulated PA
signals demonstrated close similarity with the measured PA signals, and the optical absorption coefficients of the blood
vessel phantoms were quantified with root mean square error of 2.42 cm-1.
KEYWORDS: Absorption, Continuous wavelet transforms, Wavelets, Tissue optics, Ultrasonography, Sensors, Signal attenuation, Signal generators, Signal to noise ratio, Scattering
In photo-acoustic (PA) imaging, valuable medical applications based on optical absorption spectrum such as contrast
agent imaging and blood oxygen saturation measurement have been investigated. In these applications, there is an
essential requirement to determine optical absorption coefficients accurately. In present, PA signal intensities have been
commonly used to determine optical absorption coefficients. This method achieves practical accuracy by combining with
radiative transfer analysis. However, time consumption of radiative transfer analysis and effects of signal generation
efficiencies were problems of this method. In this research, we propose a new method to determine optical absorption
coefficients using continuous wavelet transform (CWT). We used CWT to estimate instantaneous frequencies of PA
signals which reflects optical absorption distribution. We validated the effectiveness of CWT in determination of optical
absorption coefficients through an experiment. In the experiment, planar shaped samples were illuminated to generate
PA signal. The PA signal was measured by our fabricated PA probe in which an optical fiber and a ring shaped P(VDFTrFE)
ultrasound sensor were coaxially aligned. Optical properties of samples were adjusted by changing the
concentration of dye solution. Tunable Ti:Sapphire laser (690 - 1000 nm) was used as illumination source. As a result,
we confirmed strong correlation between optical absorption coefficients of samples and the instantaneous frequency of
PA signal obtained by CWT. Advantages of this method were less interference of light transfer and signal generation
efficiency.
Photoacoustics has been widely studied as a combined imaging modality of both optical and acoustical
methods. The merits of the photoacoustic imaging are realizing the full potentials of pulsed laser-tissue
interaction. As the photoacoustic waves can be induced at chromophores by pulsed lased irradiation
through a thermoelastic process, it covers a wide range of frequency. In order to take advantages of the
wide range frequency characteristics, we employed not PZT, but piezoelectronic copolymer film,
P(VDF/TrFE) film, with various thickness ranging from 20 to 100 μm as photoacoustic transducers.
Because blood vessels play a key role in homeostasis, we experimentally demonstrated blood vessels
phantom using second harmonic generation of Q-switched Nd:YAG laser and Ti:sapphire nanosecond
laser pulses through optical fiber transmission. The detected photoacoustic waveforms showed
distinctive time-of-flight signals. The photoacoustic signals were sensitive to temperature, absorption
coefficients of chromophores, and diameters of the phantom vessels. Hemoglobin oxygen saturation could
be easily derived from the multi wavelength photoacoustic signals using differential optical absorption
characteristics. These results proved the functional quantitative photoacoustic imaging using the signal
characteristics. A multivariate photoacoustic imaging approach must be promising to convenient
diagnosis.
Our goal is to develop a photo-acoustic imaging (PAI) system which offers functional image of living tissues and
organs with high resolution. In order to obtain high resolution image, we implemented the Fourier transform
reconstruction algorithm which determines an optical absorption distribution from photo-acoustic (PA) signals. However,
resolutions of reconstructed images were restricted by the sensor directionality, finite scan width and frequency band
width. There was an essential requirement to optimize the sensor specification. In this study, we demonstrated
relationship between image resolution and sensor specification by simulation and experiment. In our experimental
system, PA signals were acquired by line scanning of our fabricated P(VDF/TrFE) film sensor. As results of simulations
and experiments, lateral resolutions of PA images were restricted by the directionality of sensor. Furthermore, by
limiting scan width and frequency band width, lateral resolution is decreased at deep region. The optimum sensor
specification depends on the imaging region due to some trade-offs, for example, a sensor with wider directionality has
less sensitivity, wider scan in same step increases acquisition time. Therefore, the results could indicate the possibility of
optimizing sensor directionality, scan width and frequency band width for various depths and volumes of imaging region.
To develop the catheter-based laser vascular welding device against aortic dissection, we studied fundamental characteristics of the laser vascular welding for aorta dissection model in vitro with the scattering light monitoring to obtain welding proceedings. We employed the laser vascular welding by means of the combination of the diode laser irradiation and indocyanine green (ICG) stain to the dissected vessel surface in a swine aortic dissection model to obtain localized heat generation on the surface. The forward and backward scattering lights of the diode laser from the welding portion were measured during the laser irradiation. The breaking stresses of the welded aortic pieces were measured. The breaking stress of 170gf/cm2 obtained with the 425W/cm2, 2.4s irradiation may be strong enough to the successful therapy for aortic dissection regarding to the dissecting force caused by blood flow. By analyzing forward and backward scattering lights, we could observe the occurrence of water evaporation in the welding portion, the bleaching of the ICG and the carbonization of the welding portion. Then we could monitor the proceedings of the welding process. The temperature estimation of the welding portion and the microscopic observation revealed that the mechanism of our welding may be basically elastic fiber entwining. We think our vascular welding with the scattering light monitoring of the welding process has the potential to apply catheter-based therapy for aortic dissection.
This paper reports the burn diagnosis that is based on the measurement of photoacoustic waves from skin, where the acoustic waves originate from the absorption of light by blood. For this purpose, a transducer composed of a ring-shaped piezoelectric film and a quartz fiber was made. An optical parametric oscillator (500 - 650 nm) was used as a light source and its output pulses were coupled to the quartz fiber. To investigate the optimum light wavelength, we conducted experiments using rat burn models. We demonstrated that the superficial dermal burn (SDB), deep dermal burn (DDB), deep burn (DB), and control (healthy skin) could be clearly differentiated based on the photoacoustic signals induced by the light of 532 - 580nm.
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