Micromachined Silicon Parallel Acoustic Delay Lines as Time Delayed Ultrasound Detector Array for Real-Time Photoacoustic Tomography.

This paper reports the development of a new 16-channel parallel acoustic delay line (PADL) array for real-time photoacoustic tomography (PAT). The PADLs were directly fabricated from single-crystalline silicon substrates using deep reactive ion etching. Compared with other acoustic delay lines (e.g., optical fibers), the micromachined silicon PADLs offer higher acoustic transmission efficiency, smaller form factor, easier assembly, and mass production capability. To demonstrate its real-time photoacoustic imaging capability, the silicon PADL array was interfaced with one single-element ultrasonic transducer followed by one channel of DAQ electronics to receive 16 channels of photoacoustic signals simultaneously. A PAT image of an optically-absorbing target embedded in an optically-scattering phantom was reconstructed, which matched well with the actual size of the imaged target. Because the silicon PADL array allows a signal-to-channel reduction ratio of 16:1, it could significantly simplify the design and construction of ultrasonic receivers for real-time PAT.

High-Transmission-Efficiency and Side-Viewing Micro OIDRS Probe for Fast and Minimally-Invasive Tumor Margin Detection.

The determination of a cancer free margin I organs is a difficult and time consuming process, with an unmet need for rapid determination of tumor margin at surgery. In this paper, we report the design, fabrication and testing of a novel miniaturized optical sensor probe with "side-viewing" capability. Its unprecedented small size, unique "side-viewing" capability and high optical transmission efficiency enable the agile maneuvering and efficient data collection even in the narrow cavities inside the human body. The sensor probe consists of four micromachined substrates with optical fibers for oblique light incidence and collection of spatially resolved diffuse reflectance from the contacted tissues. The optical sensor probe has been used to conduct the oblique incidence diffuse reflectance spectroscopy (OIDRS) on a human pancreatic specimen. Based on the measurement results, the margin of the malignant tumor has been successfully determined optically, which matches well with the histological results.

Micromachined "Side-Viewing" Optical Sensor Probe for Detection of Esophageal Cancers.

In this paper, we report the design, fabrication and testing of a new miniaturized optical sensor probe with "side viewing" capability for oblique incidence diffuse reflectance spectrometry. The sensor probe consists of a lithographically patterned polymer waveguides chip and two micromachined positioning substrates and source/collection fibers to achieve 45° light incidence and collection of spatially resolved diffuse reflectance. Diffuse reflectance of human esophageal surface has been successfully measured for differentiation of cancerous tissues from normal ones.

Realtime photoacoustic microscopy of murine cardiovascular dynamics.

Non-invasive visualization of cardiovascular dynamics in small animals is challenging due to their rapid heart-rates. We present a realtime photoacoustic imaging system consisting of a 30-MHz ultrasound array transducer, receive electronics, a high-repetition-rate laser, and a multicore-computer, and demonstrate its ability to image optically-absorbing structures of the beating hearts of young athymic nude mice at rates of approximately 50 frames per second with 100 microm x 25 microm spatial resolution. To our knowledge this is the first report of realtime photoacoustic imaging of physiological dynamics.

Microwave-induced thermoacoustic tomography using multi-sector scanning.

A study of microwave-induced thermoacoustic tomography of inhomogeneous tissues using multi-sector scanning is presented. A short-pulsed microwave beam is used to irradiate the tissue samples. The microwave absorption excites time-resolved acoustic waves by thermoelastic expansion. The amplitudes of the acoustic waves are strongly related to locally absorbed microwave-energy density. The acoustic waves may propagate in all spatial directions. A focused ultrasonic transducer is employed to acquire temporal acoustic signals from multiple directions. Each detected signal is converted into a one-dimensional (1D) image along the acoustic axis of the transducer. The cross-sectional images of the tissue samples are calculated by combining all of the 1D images acquired in the same planes.

Signal processing in scanning thermoacoustic tomography in biological tissues.

Microwave-induced thermoacoustic tomography was explored to image biological tissues. Short microwave pulses irradiated tissues to generate acoustic waves by thermoelastic expansion. The microwave-induced thermoacoustic waves were detected with a focused ultrasonic transducer to obtain two-dimensional tomographic images of biological tissues. The dependence of the axial and the lateral resolutions on the spectra of the signals was studied. A reshaping filter was applied to the temporal piezoelectric signals from the transducer to increase the weight of the high-frequency components, which improved the lateral resolution, and to broaden the spectrum of the signal, which enhanced the axial resolution. A numerical simulation validated our signal-processing approach.

Mechanisms of ultrasonic modulation of multiply scattered coherent light: an analytic model.

An analytic model of the ultrasonic modulation of multiply scattered coherent light in scattering media is developed based on two mechanisms: the ultrasonic modulation of the index of refraction and the ultrasonic modulation of the displacements of Rayleigh scatterers. In water solutions, for example, the first mechanism is slightly less important than the second mechanism when the scattering mean free path is less than a critical fraction (0.0890) of the acoustic wavelength, and it becomes increasingly more important beyond this point. This model agrees well with an independent Monte Carlo model.

Optical-thermal simulation of tonsillar tissue irradiation.

BACKGROUND AND OBJECTIVE: Despite laser applications targetted toward tonsillar tissue, there has been no characterization of underlying optical and thermal events during laser irradiation of tonsillar tissue. STUDY DESIGN/MATERIALS AND METHODS: The optical properties of canine and human tonsils were determined at 805 nm (diode laser) and 1,064 nm (Nd:YAG laser). An optical-thermal simulation was developed to predict the temperature rise in irradiated human tonsils. RESULTS: The optical properties of human and canine tonsillar tissue are similar at both wavelengths. The optical-thermal simulation was validated and predicts that at 10 W and 1 minute of irradiation, the heat will be contained within the human tonsil. The diode laser causes more superficial heating than the Nd:YAG laser. CONCLUSIONS: The safety of irradiating human tonsils was shown. The diode laser is superior to the Nd:YAG laser because less heat affects collateral structures. The optical-thermal simulation detailed in this study can be used to predict the temperature rise in tissues undergoing irradiation.

Scanning microwave-induced thermoacoustic tomography: signal, resolution, and contrast.

Scanning thermoacoustic tomography was explored in the microwave region of the electromagnetic spectrum. Short microwave pulses were used to induce acoustic waves by thermoelastic expansion in biological tissues. Cross sections of tissue samples were imaged by a linear scan of the samples while a focused ultrasonic transducer detected the time-resolved thermoacoustic signals. Based on the microwave-absorption properties of normal and cancerous breast tissues, the piezoelectric signals in response to the thermoacoustic contrast were investigated over a wide range of electromagnetic frequencies and depths of tumor locations. The axial resolution is related to the temporal profile of the microwave pulses and to the impulse response of the ultrasonic transducer. The lateral resolution is related to the numerical aperture of the ultrasonic transducer as well as to the frequency spectra of the piezoelectric signals in the time window corresponding to the axial resolution. Gain compensation, counteracting the microwave attenuation, was applied to enhance the image contrast.

Microwave-induced thermoacoustic tomography: reconstruction by synthetic aperture.

We have applied the synthetic-aperture method to linear-scanning microwave-induced thermoacoustic tomography in biological tissues. A nonfocused ultrasonic transducer was used to receive thermoacoustic signals, to which the delay-and-sum algorithm was applied for image reconstruction. We greatly improved the lateral resolution of images and acquired a clear view of the circular boundaries of buried cylindrical objects, which could not be obtained in conventional linear-scanning microwave-induced thermoacoustic tomography based on focused transducers. Two microwave sources, which had frequencies of 9 and 3 GHz, respectively, were used in the experiments for comparison. The 3 GHz system had a much larger imaging depth but a lower signal-noise ratio than the 9 GHz system in near-surface imaging.

Mechanisms of ultrasonic modulation of multiply scattered coherent light: a Monte Carlo model.

A Monte Carlo model of the ultrasonic modulation of multiply scattered coherent light in scattering media is provided. The model is based on two mechanisms: the ultrasonic modulation of the index of refraction, which causes a modulation of the optical path lengths between consecutive scattering events, and the ultrasonic modulation of the displacements of scatterers, which causes a modulation of optical path lengths with each scattering event. Multiply scattered light accumulates modulated optical path lengths along its path. Consequently, the intensity of the speckles that are formed by the multiply scattered light is modulated. The contribution from the index of refraction is comparable with the contribution from displacement when the acoustic-wave vector is less than a critical fraction of the transport mean free path and becomes increasingly greater than the contribution from displacement beyond this critical point. This Monte Carlo model agrees well with an independent analytical model for isotropically scattering media. Both mechanisms are coherent phenomena, requiring the use of a coherent light source.

Optical-thermal simulation of human tonsillar tissue irradiation: clinical implications.

BACKGROUND AND OBJECTIVE: Mucosa intact laser tonsillar ablation is an alternative to conventional tonsillectomy. The efficacy of this procedure was demonstrated in canines, but establishing the safety of irradiating human tonsils is paramount. STUDY DESIGN/MATERIALS AND METHODS: An optical-thermal simulation of tonsillar tissue irradiation was previously developed, but the effect of varying parameters was not investigated. The tissue response to irradiation at 5-25 watts for 1 minute and 10 watts for 10 seconds to 162 seconds is simulated. RESULTS: At 15 watts and greater, the peak temperature is over 100 degrees C and the mucosal temperature is over 70 degrees C. At the depth of the tonsil, the temperature does not vary significantly. The peak temperature is at 1 mm. The radial temperature profile is not significantly altered by longer irradiation times. CONCLUSIONS: The optimal dosimetry parameters for irradiation of human tonsillar tissue at 805 nm with the MILTA technique is under 15 watts for approximately 1 minute.

Scanning thermoacoustic tomography in biological tissue.

Microwave-induced thermoacoustic tomography was explored to image biological tissue. Short microwave pulses irradiated tissue to generate acoustic waves by thermoelastic expansion. The microwave-induced thermoacoustic waves were detected with a focused ultrasonic transducer. Each time-domain signal from the ultrasonic transducer represented a one-dimensional image along the acoustic axis of the ultrasonic transducer similar to an ultrasonic A-scan. Scanning the system perpendicularly to the acoustic axis of the ultrasonic transducer would generate multi-dimensional images. Two-dimensional tomographic images of biological tissue were obtained with 3-GHz microwaves. The axial and lateral resolutions were characterized. The time-domain piezo-electric signal from the ultrasonic transducer in response to the thermoacoustic signal was simulated theoretically, and the theoretical result agreed with the experimental result very well.

Source of error in calculation of optical diffuse reflectance from turbid media using diffusion theory.

Diffusion theory and similarity relations were used to calculate the optical diffuse reflectance of an infinitely narrow laser beam incident upon a semi-infinite turbid medium. The results were analyzed by comparison with the accurate results from Monte Carlo simulations. Because a large number of photon packets were traced, the variance of the results from Monte Carlo simulations was small enough to reveal the detailed defects of the diffusion theory and the similarity relations, which are broadly used in photomedicine. We demonstrated that both diffusion theory and similarity relations provide very accurate results when the photon sources are isotropic and buried more deeply than one transport mean free path in turbid media. We found that the key factor affecting the accuracy of the diffusion theory application was the conversion from the infinitely narrow laser beam to an isotropic point source in turbid media.

Frequency-swept ultrasound-modulated optical tomography in biological tissue by use of parallel detection.

A frequency-swept ultrasonic beam was focused into a biological tissue sample to modulate the laser light passing through the ultrasonic beam inside the tissue. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and can be used for tomographic imaging of the tissue. Sweeping the ultrasonic frequency provides spatial resolution along the ultrasonic axis, which is scalable with the frequency span of the sweep. Two-dimensional images of biological tissue with buried objects were successfully obtained experimentally.

Theoretical and experimental studies of ultrasound-modulated optical tomography in biological tissue.

Ultrasound-modulated optical tomography in biological tissue was studied both theoretically and experimentally. An ultrasonic beam was focused into biological tissue samples to modulate the laser light passing through the ultrasonic beam inside the tissue. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and permits tomographic imaging of biological tissues by scanning. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. Two-dimensional images of biological tissues were successfully obtained experimentally with a laser beam at either normal or oblique incidence, which showed that ultrasound-modulated optical tomography depends on diffuse light rather than on ballistic light. Monte Carlo simulations showed that the modulation depth decreased much more slowly than the diffuse transmittance, which indicated the possibility that even thicker biological tissues can be imaged with this technique.

Depth-resolved two-dimensional stokes vectors of backscattered light and mueller matrices of biological tissue measured with optical coherence tomography.

Mueller matrices provide a complete characterization of the optical polarization properties of biological tissue. A polarization-sensitive optical coherence tomography (OCT) system was built and used to investigate the optical polarization properties of biological tissues and other turbid media. The apparent degree of polarization (DOP) of the backscattered light was measured with both liquid and solid scattering samples. The DOP maintains the value of unity within the detectable depth for the solid sample, whereas the DOP decreases with the optical depth for the liquid sample. Two-dimensional depth-resolved images of both the Stokes vectors of the backscattered light and the full Mueller matrices of biological tissue were measured with this system. These polarization measurements revealed some tissue structures that are not perceptible with standard OCT.

Full-field mapping of ultrasonic field by light-source-synchronized projection.

A simple method for imaging ultrasonic fields in clear media is introduced. A modulated laser source is used to project the ultrasonic field onto a CCD camera. By use of the source-synchronized lock-in detection scheme, 2D images of the amplitude and phase distributions can be determined simultaneously. This technique is experimentally demonstrated with a 1-MHz and a 3.5-MHz ultrasonic transducer operated in continuous-wave mode. This method is very straightforward to implement and can be combined with the traditional tomographic reconstruction technique to obtain the 3D distribution of an ultrasonic field.

Monte Carlo simulation of an optical coherence tomography signal in homogeneous turbid media.

The Monte Carlo technique with angle biasing is used to simulate the optical coherence tomography (OCT) signal from homogeneous turbid media. The OCT signal is divided into two categories: one is from a target imaging layer in the medium (Class I); the other is from the rest of the medium (Class II). These two classes of signal are very different in their spatial distributions, angular distributions and the numbers of experienced scattering events. Multiply scattered light contributes to the Class I signal as well as the Class II signal. The average number of scattering events increases linearly with the probing depth. The Class II signal decays much more slowly than the Class I signal whose decay constant is close to the total attenuation coefficient of the turbid medium. The effect of the optical properties of the medium on the Class I signal decay is studied.

Development of tissue-simulating optical phantoms: poly-N-isopropylacrylamide solution entrapped inside a hydrogel.

The average turbid optical properties of the N-isopropylacrylamide (NIPA) polymer solution entrapped inside a polyacrylamide hydrogel (called an NIPA/PAAM gel system) were studied using a multiwavelength oblique-incidence reflectometer. The turbidity of such a system can be drastically changed by simply switching the temperature from below the low critical solution temperature of the NIPA, around 33 degrees C, to above. The absorption coefficient and the reduced scattering coefficient were obtained as a function of wavelength for samples with selected NIPA and blue dextran concentrations. It is found that the scattering of the optical phantom comes from the NIPA polymer chains and the absorption from the blue dextran. The turbid optical properties of an NIPA/PAAM gel system can be tuned to simulate biological tissues at a specific wavelength by varying compositions of NIPA and blue dextran and further modified by controlling the temperature.