Prospective tissue-mimicking materials for use in NMR imaging phantoms

Water-based proteinaceous gels, which—with appropriate additives—are stable with time and possess a high melting point, have been used as base materials in ultrasonically tissue-mimicking materials. In the present work, versions of these gels having various concentrations of glycerol and graphite particles were studied regarding their NMR T₁ and T₂ dependencies at a proton Larmor frequency of 10.7 MHz. It has been found that T₁ depends primarily on the concentration of glycerol and T₂ depends primarily on the graphite particle concentration. Also, the ranges of T₁ and T₂ likely span those which exist for soft tissue parenchymae. Thus, these materials are good candidates for use as NMR tissue-mimicking materials. T₁ and T₂ also vary with gelatin concentration. The latter fact, together with the strong dependence of T₂ on graphite concentration, mean that effective contrast-resolution phantoms and anthropomorphic phantoms with stable T₁ and T₂ distributions can be produced.     

Enhanced peptide molecular imaging using aqueous droplets

A new method in time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging, the droplet-enhanced method, was developed for the molecular analysis of biomaterials. To facilitate the ionization of biomolecules, a small amount of aqueous solution containing a variety of protonation agents as ionization-enhancing agents was dropped onto peptide samples before ToF-SIMS measurement. Using trifluoroacetic acid (TFA) as an enhancing agent, protonated insulin (MW 5733) ions were detected as not only [M + H]⁺ but also [M + 2H]²⁺ and [M + 3H]³⁺ from its film sample, using a Ga⁺ primary beam. TFA promoted the ionization of the large molecules much more effectively than did the other acids, and this peculiarity is related to both Na⁺ and Au₃⁺ intensities. We also demonstrated the visualization of dot-patterned insulin drawn with our bubble jet (BJ) printing technology using insulin molecular ion signals.     

Sizing of emulsion droplets under flow using flow-compensating NMR-PFG techniques

Using the nuclear magnetic resonance (NMR) pulsed field gradient (PFG) technique, it is possible to determine the size distribution of emulsion droplets. This method is extended so that the same measurements can be performed in the presence of flow. The resultant flow-compensating NMR-PFG technique is used to determine the oil droplet-size distribution of an oil-in-water emulsion flowing in a narrow tube at various flow rates. Comparison with the nonflowing oil droplet-size distribution enables the effect of velocity shear on the oil droplet-size distribution to be quantified.     

Absolute backscatter coefficient estimates of tissue-mimicking phantoms in the 5-50 MHz frequency range

Absolute backscatter coefficients in tissue-mimicking phantoms were experimentally determined in the 5-50 MHz frequency range using a broadband technique. A focused broadband transducer from a commercial research system, the VisualSonics Vevo 770, was used with two tissue-mimicking phantoms. The phantoms differed regarding the thin layers covering their surfaces to prevent desiccation and regarding glass bead concentrations and diameter distributions. Ultrasound scanning of these phantoms was performed through the thin layer. To avoid signal saturation, the power spectra obtained from the backscattered radio frequency signals were calibrated by using the signal from a liquid planar reflector, a water-brominated hydrocarbon interface with acoustic impedance close to that of water. Experimental values of absolute backscatter coefficients were compared with those predicted by the Faran scattering model over the frequency range 5-50 MHz. The mean percent difference and standard deviation was 54%?±?45% for the phantom with a mean glass bead diameter of 5.40 μm and was 47%?±?28% for the phantom with 5.16 μm mean diameter beads.     

Study of ultrasound stiffness imaging methods using tissue mimicking phantoms

A pilot study was carried out to investigate the performance of ultrasound stiffness imaging methods namely Ultrasound Elastography Imaging (UEI) and Acoustic Radiation Force Impulse (ARFI) Imaging. Specifically their potential for characterizing different classes of solid mass lesions was analyzed using agar based tissue mimicking phantoms. Composite tissue mimicking phantom was prepared with embedded inclusions of varying stiffness from 50 kPa to 450 kPa to represent different stages of cancer. Acoustic properties such as sound speed, attenuation coefficient and acoustic impedance were characterized by pulse echo ultrasound test at 5 MHz frequency and they are ranged from (1564 ± 88 to 1671 ± 124 m/s), (0.6915 ± 0.123 to 0.8268 ± 0.755 db cm^-1 MHz^-1) and (1.61×10⁶ ± 0.127 to 1.76 × 10⁶ ± 0.045 kg m^-2 s^-1) respectively. The elastic property Young’s Modulus of the prepared samples was measured by conducting quasi static uni axial compression test under a strain rate of 0.5 mm/min upto 10 % strain, and the values are from 50 kPa to 450 kPa for a variation of agar concentration from 1.7% to 6.6% by weight. The composite phantoms were imaged by Siemens Acuson S2000 (Siemens, Erlangen, Germany) machine using linear array transducer 9L4 at 8 MHz frequency; strain and displacement images were collected by UEI and ARFI. Shear wave velocity 4.43 ± 0.35 m/s was also measured for high modulus contrast (18 dB) inclusion and X.XX m/s was found for all other inclusions. The images were pre processed and parameters such as Contrast Transfer Efficiency and lateral image profile were computed and reported. The results indicate that both ARFI and UEI represent the abnormalities better than conventional US B mode imaging whereas UEI enhances the underlying modulus contrast into improved strain contrast. The results are corroborated with literature and also with clinical patient images.     

Quantitative imaging of mixing dynamics in microfluidic droplets using two-photon fluorescence lifetime imaging

Droplet-based microfluidic systems enable miniaturization of chemical reactions in femtoliter to picoliter volume compartments. Quantifying mixing dynamics of the reagents in droplets is critical to determine the system performance. In this Letter, we developed a two-photon excitation fluorescence lifetime imaging technique to quantitatively image the mixing dynamics in micro?uidic droplets. A cross/autocorrelation method was used to reconstruct a high-quality fluorescence lifetime image of the droplet. The fluorescence decay was analyzed for accurate determination of the mixing ratio at each pixel of the image.     

光声成像技术的最新进展

光声成像技术是生物医学领域中新兴的无损检测技术,具有对比度高、分辨率好、穿透能力强等优点.本文介绍了光声成像技术近年来的进展状况,主要涉及成像探测方式的改进、成像速度的加快、成像分辨率的提高以及图像重构算法的发展等.以该项技术在现代临床诊断中的应用为例,描述了其在生物医学领域中应用范围的拓宽.最后,总结了该项技术现存的...     

Remote photoacoustic imaging on solid material using a two-wave mixing interferometer

We report on remote and contactless photoacoustic imaging (PAI) for the inspection of solid materials using a two-wave mixing interferometer. In this Letter, a semitransparent sample was excited with picosecond laser pulses. The local absorption of the electromagnetic radiation led to generation of broadband ultrasonic waves inside the sample. Ultrasonic waves arriving at the sample surface were detected utilizing a two-wave mixing interferometer. After data acquisition, the initial pressure distribution was reconstructed using a Fourier space synthetic aperture technique algorithm. We show the potential of PAI for the inspection of semitransparent solid materials.     

生物医学光声成像的研究进展

光声成像是21世纪初发展起来的新兴的生物医学成像技术,它同时具备光学成像和声学成像两者的优点,因而备受关注。本文对生物医学光声成像的发展进行了综述。首先,介绍了光声成像的特点以及相对于广泛应用的光学成像技术和声学成像技术的优点;其次,在成像原理上解释了光声成像优点的成因,并介绍了光声断层成像和光声显微镜这两种典型的光声成像技术;再次,详细介绍了多尺度的光声图像分辨率和成像深度,以及多信息维度的光声成像参数;最后,展望了光声成像在生物医学领域的应用潜力并讨论了其局限性。     

Fundamental precision limitations for measurements of frequency dependence of backscatter: applications in tissue-mimicking phantoms and trabecular bone.

Various models for ultrasonic scattering from trabecular bone have been proposed. They may be evaluated to a certain extent by comparison with experimental measurements. In order to appreciate limitations of these comparisons, it is important to understand measurement precision. In this article, an approach proposed by Lizzi and co-workers is adapted to model precision of estimates of frequency-dependent backscatter for scattering targets (such as trabecular bone) that contain many scatterers per resolution cell. This approach predicts uncertainties in backscatter due to the random nature of the interference of echoes from individual scatterers as they are summed at the receiver. The model is validated in experiments on a soft-tissue-mimicking phantom and on 24 human calcaneus samples interrogated in vitro. It is found that while random interference effects only partially explain measured variations in the magnitude of backscatter, they are virtually entirely responsible for observed variations in the frequency dependence (exponent of a power law fit) of backscatter.     

Nonlinear imaging of isoechogenic phantoms using phase conjugation of the second acoustic harmonic

Experiments on nonlinear C-scan acoustic imaging were performed using phase conjugation of the second harmonic of a focused incident beam. This method made it possible to obtain images of objects with close linear properties but with different nonlinear parameters. Nonlinear backward propagation of the conjugate wave was also considered and improvement of the image contrast was demonstrated for this case. The results obtained were generally in agreement with the theoretical predictions.     

Imaging contrast effects in alginate microbeads containing trapped emulsion droplets

This study focuses on spherical microparticles made of cross-linked alginate gel and microcapsules composed of an oil-in-water emulsion where the continuous aqueous phase is cross-linked into an alginate gel matrix. We have investigated the use of these easily manufactured microbeads as contrast agents for the study of the flow properties of fluids using nuclear magnetic resonance imaging. Results demonstrate that combined spin-spin (T(2)) relaxation and diffusion contrast in proton NMR imaging can be used to distinguish among rigid polymer particles, plain alginate beads, and alginate emulsion beads. Multi-echo CPMG spin-echo imaging indicates that the average spin-lattice (T(1)) and spin-spin (T(2)) relaxation times of the plain alginate and alginate emulsion beads are comparable. Meanwhile, diffusion-weighted imaging produces sharp contrast between the two types of alginate beads, due to restricted diffusion inside the embedded oil droplets of the alginate emulsion beads. While the signal obtained from most materials is severely attenuated under applied diffusion gradients, the alginate emulsion beads maintain signal strength. The alginate emulsion beads were added to a suspension and imaged in an abrupt, annular expansion flow. The emulsion beads could be clearly distinguished from the surrounding suspending fluid and rigid polystyrene particles, through either T(2) relaxation or diffusion contrast. Such a capability allows future use of the alginate emulsion beads as tracer particles and as one particle type among many in a multimodal suspension where detailed concentration profiles or particle size separation must be quantified during flow.     

Lensless high-resolution photoacoustic imaging scanner for in vivo skin imaging

We previously launched a high-resolution photoacoustic (PA) imaging scanner based on a unique lensless design for in vivo skin imaging. The design, imaging algorithm and characteristics of the system are described in this paper. Neither an optical lens nor an acoustic lens is used in the system. In the imaging head, four sensor elements are arranged quadrilaterally, and by checking the phase differences for PA waves detected with these four sensors, a set of PA signals only originating from a chromophore located on the sensor center axis is extracted for constructing an image. A phantom study using a carbon fiber showed a depth-independent horizontal resolution of 84.0 ± 3.5 µm, and the scan direction-dependent variation of PA signals was about ± 20%. We then performed imaging of vasculature phantoms: patterns of red ink lines with widths of 100 or 200 μm formed in an acrylic block co-polymer. The patterns were visualized with high contrast, showing the capability for imaging arterioles and venues in the skin. Vasculatures in rat burn models and healthy human skin were also clearly visualized in vivo.     

Simulation of light delivery for photoacoustic breast imaging using the handheld probe

The photoacoustic tomography by using the handheld probe has a great potential in clinical breast imag- ing. However, tile shape of the probe limits the choice of light delivery in this setup. In this letter, we study two commonly used illumination types for handheld probe： bright-field illumination and dark-field illumination. Our results demonstrate several parameters have important impact on the photon fluence in deep breast tissue. The results will help to optimize the design of the photoaeoustie breast imaging system with a handheld probe.     

2D-temperature imaging of single droplets and sprays using thermographic phosphors

A novel 2D-technique for temperature visualization of single droplets and sprays is presented. Laser induced emission from thermographic phosphor seeded to the investigated liquid was detected by a fast framing camera. The subsequent phosphorescence images measured by seven consecutively gated CCD detectors allowed pixel-to-pixel lifetime evaluation of the phosphorescence emission. The temperature at each pixel position was evaluated using a calibration procedure of temperature against lifetime. These measurements were applied first to a free falling water based droplet, then to a suspended droplet in an ultrasonic levitator. Finally, the technique was applied to spray. PACS 07.20.Dt; 46.65.Fi; 32.50.+d; 43.25.Uv; 34.50.Gb     

Laser Doppler imaging through tissues phantoms by using self-mixing interferometry with a laser diode

Laser Doppler imaging has been widely used for the evaluation of cutaneous blood flow. We report on how the self-mixing interferometry configuration with a laser diode is explored for what is believed to be the first time to generate flow maps. The experiment was carried out by sensing the laser intensity power spectrum at each pixel as the laser was scanned over a model that mimics the properties of skin and circulating blood.     

Noncontact photoacoustic imaging achieved by using a low-coherence interferometer as the acoustic detector

We report on a noncontact photoacoustic imaging (PAI) technique in which a low-coherence interferometer [(LCI), optical coherence tomography (OCT) hardware] is utilized as the acoustic detector. A synchronization approach is used to lock the LCI system at its highly sensitive region for photoacoustic detection. The technique is experimentally verified by the imaging of a scattering phantom embedded with hairs and the blood vessels within a mouse ear in vitro. The system's axial and lateral resolutions are evaluated at 60 and 30?μm, respectively. The experimental results indicate that PAI in a noncontact detection mode is possible with high resolution and high bandwidth. The proposed approach lends itself to a natural integration of PAI with OCT, rather than a combination of two separate and independent systems.     

Three-dimensional photoacoustic imaging of blood vessels in tissue

We applied photoacoustics as a tissue tomography technique for the detection of blood concentrations, e.g., angiogenesis around tumors. We imaged blood vessels in highly scattering samples, using 532-nm light, to depths of ~1 cm . The samples were real tissue (chicken breast) or 10% dilutions of Intralipid-10%. The blood flowed through nylon capillaries. Polyvinylidene difluoride (PVdF) piezoelectric detectors were used in a surface-scanning mode. We demonstrate the sensitivity of the technique by photoacoustic detection of single red blood cells upon a glass plate. Lateral resolution is limited by the detector diameter (200 microm). The depth resolution is ~10 microm.     

Utility of biodegradable plasmonic nanoclusters in photoacoustic imaging

Plasmonic metal nanoparticles are used in photoacoustic imaging as contrast agents because of their resonant optical absorption properties in the visible and near-IR regions. However, the nanoparticles could accumulate and result in long-term toxicity in vivo, because they are generally not biodegradable. Recently, biodegradable plasmonic gold nanoclusters, consisting of sub-5 nm primary gold nanoparticles and biodegradable polymer stabilizer, were introduced. In this Letter, we demonstrate the feasibility of biodegradable nanoclusters as a photoacoustic contrast agent. We performed photoacoustic and ultrasound imaging of a tissue-mimicking phantom with inclusions containing nanoclusters at various concentrations. The results indicate that the biodegradable gold nanoclusters can be used as effective contrast agents in photoacoustic imaging.     

多参量光声成像及其在生物医学领域的应用

光声成像兼具声学成像和光学成像两者的优点, 因而成为近十年来发展最迅速的生物医学成像技术之一. 本文介绍了光声成像的特点及其相对于广泛应用的光学成像技术和声学成像技术的优点; 其次, 解释了光声成像的成像原理, 在此基础上介绍了光声断层成像和光声显微镜这两种典型的光声成像方案, 并介绍了它们的技术特点; 然后, 介绍了光声成像对生物组织的生化特性、组织力学特性、血液流速分布、温度分布参数、微结构特性等多信息参量的提取能力, 及其在生物系统的结构成像、功能成像、代谢成像、分子成像、基因成像等多领域的应用; 最后, 展望了光声成像在生物医学领域的应用潜力并讨论了其局限性.