The employment of contrast agents in photoacoustic imaging has gained significant attention within the past few years
for their biomedical applications. In this study, the use of silica-coated superparamagnetic iron oxide (Fe3O4)
nanoparticles (SPION) was investigated as a contrast agent in biomedical photoacoustic imaging. SPIONs have been
widely used as Food-and-Drug-Administration (FDA)-approved contrast agents for magnetic resonance imaging (MRI)
and are known to have an excellent safety profile. Using our frequency-domain photoacoustic correlation technique
(“the photoacoustic radar") with modulated laser excitation, we examined the effects of nanoparticle size, concentration
and biological medium (e.g. serum, sheep blood) on its photoacoustic response in turbid media (intralipid solution).
Maximum detection depth and minimum measurable SPION concentration were determined experimentally. The
detection was performed using a single element transducer. The nanoparticle-induced optical contrast ex vivo in dense
muscular tissues (avian pectus) was evaluated using a phased array photoacoustic probe and the strong potential of silicacoated
SPION as a possible photoacoustic contrast agent was demonstrated. This study opens the way for future clinical
applications of nanoparticle-enhanced photoacoustic imaging in cancer therapy.
We report the development of a novel frequency-domain biomedical photoacoustic (PA) system that utilizes a
continuous-wave laser source with a custom intensity modulation pattern for spatially-resolved imaging of biological
tissues. The feasibility of using relatively long duration and low optical power laser sources for spatially-resolved PA
imaging is presented. We demonstrate that B-mode PA imaging can be performed using an ultrasonic phased array
coupled with multi-channel correlation processing and a
frequency-domain beamforming algorithm. Application of the
frequency-domain PA correlation methodology is shown using
tissue-like phantoms with embedded optical contrast,
tissue ex-vivo samples and a small animal model in-vivo.
A photoacoustic (PA) imaging methodology utilizing coded optical excitation and correlation signal processing has been
described. The basic principles of using relatively long coded waveforms and a matched filter signal compression to
increase signal-to-noise ratio (SNR) and axial resolution are common in conventional radar and sonar systems. To
emphasize these similarities, the proposed technique is called the photoacoustic sonar (or radar). We describe the
implementation of the PA sonar using a near-IR intensity modulated continuous wave laser source and frequency-domain
correlation processing of the acoustic response. Application of the PA sonar for imaging of biological materials with
discrete chromophores was studied using tissue mimicking phantoms. The SNR gain achieved with linear chirps is
analyzed and compared with conventional time-domain photoacoustics.
KEYWORDS: Acoustics, Tissues, Transducers, Signal processing, Signal to noise ratio, Modulation, Signal detection, Tissue optics, Chromophores, Absorption
The photothermoacoustic (PTA) or photoacoustic (PA) effect induced in light-absorbing materials can be observed either as a transient signal in time domain or as a periodic response to modulated optical excitation. Both techniques can be utilized for creating an image of subsurface light-absorbing structures (chromophores). In biological materials, the optical contrast information can be related to physiological activity and chemical composition of a test specimen. The present study compares experimentally the two PA imaging modalities with respect to the maximum imaging depth achieved in scattering media with optical properties similar to biological tissues. Depth profilometric measurements were carried out using a dual-mode laser system and a set of aqueous light-scattering solutions mimicking photon propagation in tissue. Various detection schemes and signal processing methods were tested to characterize the depth sensitivity of PA measurements. The obtained results demonstrate the capabilities of both techniques and can be used in specific PTA imaging applications for development of image reconstruction algorithms aimed at maximizing system performance. Our results demonstrate that submillimeter-resolution depth-selective PA imaging can be achieved without nanosecond-pulsed laser systems by appropriate modulation of a continuous laser source and a signal processing algorithm adapted to specific parameters of the PA response.
KEYWORDS: Acoustics, Signal detection, Transducers, Tissue optics, Tissues, Signal to noise ratio, Signal processing, Imaging systems, Modulation, Laser sources
A novel photothermoacoustic imaging modality utilizing a frequency-swept (chirped) intensity-modulated laser source and coherent frequency domain signal processing ("biophotoacoustics") was introduced for noninvasive imaging of biological tissues. The developed frequency-domain imaging system takes advantage of linear frequency modulation waveforms to relate depth of tissue chromophores to the frequency spectrum of the detected acoustic response and of a narrow signal detection bandwidth to improve signal-to-noise ratio (SNR). Application of frequency-domain photothermoacoustic (FD-PTA) imaging was demonstrated using turbid phantoms and ex-vivo specimens of chicken breast with embedded absorbing inclusions simulating tumors.
Recent trends in bioacoustophotonics and biothermophotonics of tissues are presented. The presentation is centered on the development of well-known frequency-domain photothermal and photoacoustic techniques to address issues associated with diffuse photon density waves during optical excitation of turbid media, both in hard tissues (teeth) and soft tissues. These methods have concrete advantages over the conventional pulsed-laser counterparts. In Part I we present biothermophotonic principles and applications to the detection of the carious state in human teeth as embodied
by laser photothermal radiometry supported by modulated luminescence. The emphasis is on the abilities of these techniques to approach important problems such as the diagnosis of occlusal pits and fissures and interproximal lesions between teeth which normally go undetected by x-ray radiographs. In Part II we present theoretical and experimental results in frequency-domain bioacoustophotonics of turbid media, such as soft tissues, and we describe the development of sensitive sub-surface imaging methodologies which hold the promise for sensitive diagnostics of cancerous lesions in e.g. a human breast. Results using tissue phantoms and ex-vivo specimens are discussed and the current level of subsurface lesion sensitivity compared to state-of-the-art pulsed photoacoustic techniques is examined. In summary, advances in coupled frequency-domain diffuse-photon-density-wave and thermal or thermoelastic responses of turbid media constitute new trends in bioacoustophotonics and biothermophotonics promising for their signal quality and high dynamic range.
KEYWORDS: Skin, Temperature metrology, Infrared cameras, Monte Carlo methods, Scattering, Absorption, Pulsed laser operation, Light scattering, Data modeling, Cameras
We have measured the Minimum Visible Lesion (MVL) thresholds for porcine skin and determined the ED50 for exposures at 1314 nm and 0.35 ms laser pulses. An in-vivo pigmented animal model, Yucatan mini-pig (Sus scrofa domestica), was used in this study. We also have measured the thermal response using a high-speed Infrared camera for single pulse temperature recordings for Gaussian beams of 1 mm diameter. Several 2-D measurements of temperature as a function of time were made with an IR array detector thermal camera using a sampling rate of 100 frames per second. In Vitro samples of the same pig skin were used for measurements of the optical properties (absorption coefficient, μa, and reduced scattering coefficient μs) as a function of wavelength around 1315 nm wavelength. A measured surface temperature distribution for one IR laser pulse of 0.37J at a spot size of 1.2 mm diameter gave approximately a 43° C rise at a hot spot. Temperature distributions as a function of time and space will be presented and compared with the measured thresholds.
Blood glucose monitoring is essential for management of diabetes especially for those patients who requires regular insulin injections. A reliable noninvasive technique may eliminate inconvenience associated with frequent skin puncture to draw blood for measurement by a standard meter. Laser-induced thermal waves in tissue and detection of resulting IR response may provide a valuable approach to development of noninvasive glucose sensor. The present report analyzes radiometric response of tissue at the two wavelengths in mid-IR spectral band with phase-sensitive detection to evaluate feasibility of differential phase radiometry for noninvasive glucose monitoring. Sensitivity of the differential phase method is computed using two models of laser-tissue interaction: homogeneous light absorption and a discrete chromophore heating.
We have developed a low-coherence optical sensor for detection of laser-induced thermoelastic deformations in biological materials. The presented optical sensor utilizes a birefringent fiber-based dual channel low-coherence Michelson interferometer capable of differential phase measurements. We demonstrate that the low-coherence sensor can be used for spatially-resolved measurements of laser-induced thermoelastic deformations in biological materials with high axial resolution. Experimental studies were carried out using gelatin-based tissue phantoms.
We demonstrate application of a thermal wave imaging technique to determine the physical dimensions and position of laser-heated chromophores in tissue. We demonstrate that utilization of a periodically modulated laser source for thermal wave excitation and coherent detection applied to each pixel may be used to compute images of thermal wave amplitude and phase at the laser modulation frequency and significantly improve quality of recorded radiometric images. A theoretical analysis utilizes solution of the three-dimensional heat conduction equation to simulate thermal wave images of amplitude and phase. Effects of non- specific laser excitation on the recorded thermal wave images have been analyzed. Results of numerical simulations are compared to that obtained from tissue phantoms and in- vivo samples.
Thermodynamic induced changes in birefringence of nasal septal cartilage following Nd:YAG laser irradiation were investigated using a polarization-sensitive optical coherence tomography (PSOCT) system. Birefringence in cartilage is due to the asymmetrical collagen fibril structure and may change if the underlying structure is disrupted due to local heat generation by absorption of laser radiation. A PSOCT instrument and an infrared imaging radiometer were used to record, respectively, depth-resolved images of the Stokes parameters of light backscattered from ex vivo porcine nasal septal cartilage and radiometric temperature following laser irradiation. PSOCT images of cartilage were recorded before (control), during, and after laser irradiation. From the measured Stokes parameters (I,Q,U, and V), an estimate of the relative phase retardation between two orthogonal polarizations was computed to determine birefringence in cartilage. Stokes parameter images of light backscattered from cartilage show significant changes due to laser irradiation. From our experiments we differentiate dehydration and thermal denaturation effects and observe the birefringence changes only in the dehydration effect. Therefore, a dynamic measurement of birefringence changes in cartilage using PSOCT as a feedback control methodology to monitor thermal denaturation is problematic in non-ablative surgical procedures such as laser assisted cartilage reshaping.
We demonstrate application of an IR imaging technique for non-contact determination of thermal diffusivity of biological materials. The IR method utilizes pulsed laser excitation to produce an initial 3D temperature distribution in tissue, and records IR images of subsequent heat diffusion. The theoretical model assumes the time-dependent temperature increase following pulsed laser exposure occurs due to independent heat diffusion in longitudinal and lateral directions. A nonlinear least-squares algorithm is used to compute the lateral point spread function for a pair of recorded IR images and determine thermal diffusivity of a test specimen. Application of the method was demonstrated using tissue phantom s and ex-vivo samples of hydrated cartilage.
In this study, we attempted to determine the critical temperature [Tc] at which accelerated stress relaxation occurred during laser mediated cartilage reshaping. During laser irradiation, mechanically deformed cartilage tissue undergoes a temperature dependent phase transformation which results in accelerated stress relaxation. When a critical temperature is attained, cartilage becomes malleable and may be molded into complex new shapes that harden as the tissue cools. Clinically, reshaped cartilage tissue can be used to recreate the underlying cartilaginous framework of structures such as the ear, larynx, trachea, and nose. The principal advantages of using laser radiation for the generation of thermal energy in tissue are precise control of both the space-time temperature distribution and time- dependent thermal denaturation kinetics. Optimization of the reshaping process requires identification of the temperature dependence of this phase transformation and its relationship to observed changes in cartilage optical, mechanical, and thermodynamic properties. Light scattering, infrared radiometry, and modulated differential scanning calorimetry (MDSC) were used to measure temperature dependent changes in the biophysical properties of cartilage tissue during fast (laser mediated) and slow (conventional calorimetric) heating. Our studies using MDSC and laser probe techniques have identified changes in cartilage thermodynamic and optical properties suggestive of a phase transformation occurring near 60 degrees Celsius.
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