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1.  Pulsed Magneto-motive Ultrasound Imaging Using Ultrasmall Magnetic Nanoprobes 
Molecular imaging  2011;10(2):102-110.
Nano-sized particles are widely regarded as a tool to study biologic events at the cellular and molecular levels. However, only some imaging modalities can visualize interaction between nanoparticles and living cells. We present a new technique, pulsed magneto-motive ultrasound imaging, which is capable of in vivo imaging of magnetic nanoparticles in real time and at sufficient depth. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce the motion within the magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. Our experiments demonstrated a sufficient contrast between normal and iron-laden cells labeled with ultrasmall magnetic nanoparticles. Therefore, pulsed magneto-motive ultrasound imaging could become an imaging tool capable of detecting magnetic nanoparticles and characterizing the cellular and molecular composition of deep-lying structures.
PMCID: PMC3101631  PMID: 21439255
2.  Ultrasound Guidance and Monitoring of Laser-Based Fat Removal 
Lasers in surgery and medicine  2008;40(10):680-687.
Background and Objectives
We report on a study to investigate feasibility of utilizing ultrasound imaging to guide laser removal of subcutaneous fat. Ultrasound imaging can be used to identify the tissue composition and to monitor the temperature increase in response to laser irradiation.
Study Design/Materials and Methods
Laser heating was performed on ex vivo porcine subcutaneous fat through the overlying skin using a continuous wave laser operating at 1,210 nm optical wavelength. Ultrasound images were recorded using a 10 MHz linear array-based ultrasound imaging system.
Results
Ultrasound imaging was utilized to differentiate between water-based and lipid-based regions within the porcine tissue and to identify the dermis-fat junction. Temperature maps during the laser exposure in the skin and fatty tissue layers were computed.
Conclusions
Results of our study demonstrate the potential of using ultrasound imaging to guide laser fat removal.
doi:10.1002/lsm.20726
PMCID: PMC2713932  PMID: 19065554
laser therapy; ultrasound imaging; thermal imaging; treatment monitoring; fat removal; body reshaping
3.  Ligand-Mediated Self-Assembly of Hybrid Plasmonic and Superparamagnetic Nanostructures 
Hybrid nanostructures with unique optical and magnetic properties have attracted considerable interest as effective mediators for medical imaging and therapy. An aqueous-based, self-assembly approach to synthesizing hybrid plasmonic-superparamagnetic nanostructures is presented. The building blocks of the hybrid nanostructure include plasmonic gold nanorods (AuNRs) and superparamagnetic iron oxide nanoparticles (SPIONs). The AuNRs were functionalized via carboxyl-bearing surface ligands, while the SPIONs were kept “bare” after synthesis via a surfactant-free, thermal decomposition reaction in triethylene glycol. Hybrid SPION-studded AuNR nanostructures were produced upon simple mixing of the components due to chemisorption of the AuNRs’ free carboxyl groups to the SPIONs’ surfaces. The reported synthesis strategy is modular in nature and can be expanded to build hybrid nanostructures with a multitude of other plasmonic nanoparticles. With tunable near-infrared absorption peaks and a sufficient number of bound SPIONs, the self-assembled hybrid nanostructures are suitable for biomedical imaging and therapy applications.
doi:10.1021/la3037549
PMCID: PMC3594096  PMID: 23362922
Hybrid nanostructures; self-assembly; gold nanoparticles; iron oxide; silica; plasmonic nanoparticles; superparamagnetic nanoparticles
4.  Thermal stability of biodegradable plasmonic nanoclusters in photoacoustic imaging 
Optics Express  2012;20(28):29479-29487.
The photothermal stability of plasmonic nanoparticles is critically important to perform reliable photoacoustic imaging and photothermal therapy. Recently, biodegradable nanoclusters composed of sub-5 nm primary gold particles and a biodegradable polymer have been reported as clinically-translatable contrast agents for photoacoustic imaging. After cellular internalization, the nanoclusters degrade into 5 nm primary particles for efficient excretion from the body. In this paper, three different sizes of biodegradable nanoclusters were synthesized and the optical properties and photothermal stability of the nanoclusters were investigated and compared to that of gold nanorods. The results of our study indicate that 40 nm and 80 nm biodegradable nanoclusters demonstrate higher photothermal stability compared to gold nanorods. Furthermore, 40 nm nanoclusters produce higher photoacoustic signal than gold nanorods at a given concentration of gold. Therefore, the biodegradable plasmonic nanoclusters can be effectively used for photoacoustic imaging and photothermal therapy.
doi:10.1364/OE.20.029479
PMCID: PMC3635696  PMID: 23388774
(170.5120) Photoacoustic imaging; (170.3880) Medical and biological imaging
5.  Photoacoustic imaging: a potential tool to detect early indicators of metastasis 
Expert review of medical devices  2013;10(1):125-134.
The metastasis of cancer is a multistage process involving complex biological interactions and difficult to predict outcomes. Accurate assessment of the extent of metastasis is critical for clinical practice; unfortunately, medical imaging methods capable of identifying the early stages of invasion and metastasis are lacking. Photoacoustic imaging is capable of providing noninvasive, real-time imaging of significant anatomical and physiological changes. indicating the progression of cancer invasion and metastasis. Preclinically, photoacoustic methods have been used to image lymphatic anatomy, including the sentinel lymph nodes, to identify circulating tumor cells within vasculature and to detect micrometastases. Progress has begun toward the development of clinically applicable photoacoustic imaging systems to assist with the determination of cancer stage and likelihood of metastatic invasion.
doi:10.1586/erd.12.62
PMCID: PMC3563674  PMID: 23278229
circulating tumor cells; lymphatic system; medical imaging; metastasis; photoacoustics; sentinel lymph node
6.  PHOTOACOUSTIC IMAGING FOR MEDICAL DIAGNOSTICS 
Acoustics today  2012;8(4):15-23.
doi:10.1121/1.4788648
PMCID: PMC3657843  PMID: 23704855
7.  Photoacoustic Imaging for Cancer Detection and Staging 
Current molecular imaging  2013;2(1):89-105.
Cancer is one of the leading causes of death in the world. Diagnosing a cancer at its early stages of development can decrease the mortality rate significantly and reduce healthcare costs. Over the past two decades, photoacoustic imaging has seen steady growth and has demonstrated notable capabilities to detect cancerous cells and stage cancer. Furthermore, photoacoustic imaging combined with ultrasound imaging and augmented with molecular targeted contrast agents is capable of imaging cancer at the cellular and molecular level, thus opening diverse opportunities to improve diagnosis of tumors, detect circulating tumor cells and identify metastatic lymph nodes. In this paper we introduce the principles of photoacoustic imaging, and review recent developments in photoacoustic imagingas an emerging imaging modality for cancer diagnosis and staging.
doi:10.2174/2211555211302010010
PMCID: PMC3769095  PMID: 24032095
Photoacoustic imaging; ultrasound; cancer; diagnosis; staging; exogenous contrast agents; spectroscopy
8.  Evaluation of gold nanotracers to track adipose-derived stem cells in a PEGylated fibrin gel for dermal tissue engineering applications 
Evaluating the regenerative capacity of a tissue-engineered device in a noninvasive and synchronous manner is critical to determining the mechanisms for success in clinical applications. In particular, directly tracking implanted cells in a three-dimensional (3D) scaffold is desirable in that it enables the monitoring of cellular activity in a specific and localized manner. The authors’ group has previously demonstrated that the PEGylation of fibrin results in a 3D scaffold that supports morphologic and phenotypic changes in mesenchymal stem cells that may be advantageous in wound healing applications. Recently, the authors have evaluated adipose-derived stem cells (ASCs) as a mesenchymal cell source to regenerate skin and blood vessels due to their potential for proliferation, differentiation, and production of growth factors. However, tracking and monitoring ASCs in a 3D scaffold, such as a PEGylated fibrin gel, have not yet been fully investigated. In the current paper, nanoscale gold spheres (20 nm) as cell tracers for ASCs cultured in a PEGylated fibrin gel were evaluated. An advanced dual-imaging modality combining ultrasound and photoacoustic imaging was utilized to monitor rat ASCs over time. The ASCs took up gold nanotracers and could be detected up to day 16 with high sensitivity using photoacoustic imaging. There were no detrimental effects on ASC morphology, network formation, proliferation, and protein expression/secretion (ie, smooth muscle α-actin, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9) associated with gold nanotracers. Therefore, utilization of gold nanotracers can be an effective strategy to monitor the regenerative process of a stem cell source in a 3D gel for vascular and dermal tissue engineering applications.
doi:10.2147/IJN.S36711
PMCID: PMC3551459  PMID: 23345978
gold nanoparticles; adipose-derived stem cells; fibrin; ultrasound and photoacoustic imaging; angiogenesis; tissue engineering
9.  Pulsed magneto-motive ultrasound imaging to detect intracellular trafficking of magnetic nanoparticles 
Nanotechnology  2011;22(41):415105.
As applications of nanoparticles in medical imaging and biomedicine rapidly expand, the interactions of nanoparticles with living cells have become an area of active interest. For example, intracellular trafficking of nanoparticles – an important part of cell-nanoparticle interaction, has been well studied using plasmonic nanoparticles and optical or optics-based techniques due to the change in optical properties of the nanoparticle aggregates. However, magnetic nanoparticles, despite their wide range of clinical applications, do not exhibit plasmonic-resonant properties and therefore their intracellular aggregation cannot be detected by optics-based imaging techniques. In this study, we investigated the feasibility of a novel imaging technique – pulsed magneto-motive ultrasound (pMMUS), to identify intracellular trafficking of endocytosed magnetic nanoparticles. In pulsed magneto-motive ultrasound imaging a focused, high intensity, pulsed magnetic field is used to excite the cells labeled with magnetic nanoparticles, and ultrasound imaging is then used to monitor the mechanical response of the tissue. We demonstrated previously that clusters of magnetic nanoparticles amplify the pMMUS signal in comparison to signal from individual nanoparticles. Here we further demonstrate that pMMUS imaging can identify interaction between magnetic nanoparticles and living cells, i.e. intracellular aggregation of nanoparticles within the cells. The results of our study suggest that pMMUS imaging can not only detect the presence of magnetic nanoparticles but also provides information about their intracellular trafficking non-invasively and in real-time.
doi:10.1088/0957-4484/22/41/415105
PMCID: PMC3471148  PMID: 21926454
Pulsed magneto-motive ultrasound imaging; superparamagnetic iron-oxide nanoparticles; macrophage; endocytosis; intracellular trafficking
10.  In vivo Ultrasound and Photoacoustic Monitoring of Mesenchymal Stem Cells Labeled with Gold Nanotracers 
PLoS ONE  2012;7(5):e37267.
Longitudinal monitoring of cells is required in order to understand the role of delivered stem cells in therapeutic neovascularization. However, there is not an imaging technique that is capable of quantitative, longitudinal assessment of stem cell behaviors with high spatial resolution and sufficient penetration depth. In this study, in vivo and in vitro experiments were performed to demonstrate the efficacy of ultrasound-guided photoacoustic (US/PA) imaging to monitor mesenchymal stem cells (MSCs) labeled with gold nanotracers (Au NTs). The Au NT labeled MSCs, injected intramuscularly in the lower limb of the Lewis rat, were detected and spatially resolved. Furthermore, our quantitative in vitro cell studies indicate that US/PA imaging is capable of high detection sensitivity (1×104 cells/mL) of the Au NT labeled MSCs. Finally, Au NT labeled MSCs captured in the PEGylated fibrin gel system were imaged in vivo, as well as in vitro, over a one week time period, suggesting that longitudinal cell tracking using US/PA imaging is possible. Overall, Au NT labeling of MSCs and US/PA imaging can be an alternative approach in stem cell imaging capable of noninvasive, sensitive, quantitative, longitudinal assessment of stem cell behaviors with high spatial and temporal resolutions at sufficient depths.
doi:10.1371/journal.pone.0037267
PMCID: PMC3353925  PMID: 22615959
11.  Advances in Clinical and Biomedical Applications of Photoacoustic Imaging 
Importance of the field
Photoacoustic imaging is an imaging modality that derives image contrast from the optical absorption coefficient of the tissue being imaged. The imaging technique is able to differentiate between healthy and diseased tissue with either deeper penetration or higher resolution than other functional imaging modalities currently available. From a clinical standpoint, photoacoustic imaging has demonstrated safety and effectiveness in diagnosing diseased tissue regions using either endogenous tissue contrast or exogenous contrast agents. Furthermore, the potential of photoacoustic imaging has been demonstrated in various therapeutic interventions ranging from drug delivery and release to image-guided therapy and monitoring.
Areas covered in this review
This article reviews the current state of photoacoustic imaging in biomedicine from a technological perspective, highlights various biomedical and clinical applications of photoacoustic imaging, and gives insights on future directions.
What the reader will gain
Readers will learn about the various applications of photoacoustic imaging, as well as the various contrast agents that can be used to assist photoacoustic imaging. This review will highlight both pre-clinical and clinical uses for photoacoustic imaging, as well as discuss some of the challenges that must be addressed to move photoacoustic imaging into the clinical realm.
Take home message
Photoacoustic imaging offers unique advantages over existing imaging modalities. The imaging field is broad with many exciting applications for detecting and diagnosing diseased tissue or processes. Photoacoustics is also used in therapeutic applications to identify and characterize the pathology and then to monitor the treatment. Although the technology is still in its infancy, much work has been done in the pre-clinical arena, and photoacoustic imaging is fast approaching the clinical setting.
doi:10.1517/17530059.2010.529127
PMCID: PMC3041963  PMID: 21344060
Atherosclerosis; cancer; contrast agents; drug delivery; molecular imaging; nanoparticles; optoacoustics; photoacoustics; therapy; ultrasound
12.  Tissue-mimicking phantoms for photoacoustic and ultrasonic imaging 
Biomedical Optics Express  2011;2(11):3193-3206.
In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin-based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid® 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies.
doi:10.1364/BOE.2.003193
PMCID: PMC3207386  PMID: 22076278
(110.3000) Image quality assessment; (160.4760) Optical properties; (170.5120) Photoacoustic imaging; (170.7170) Ultrasound; (290.5820) Scattering measurements
13.  In vivo three-dimensional spectroscopic photoacoustic imaging for monitoring nanoparticle delivery 
Biomedical Optics Express  2011;2(9):2540-2550.
Abstract
In vivo monitoring of nanoparticle delivery is essential to better understand cellular and molecular interactions of nanoparticles with tissue and to better plan nanoparticle-mediated therapies. We developed a three-dimensional ultrasound and photoacoustic (PA) imaging system and a spectroscopic PA imaging algorithm to identify and quantify the presence of nanoparticles and other tissue constituents. Using the developed system and approach, three-dimensional in vivo imaging of a mouse with tumor was performed before and after intravenous injection of gold nanorods. The developed spectroscopic PA imaging algorithm estimated distribution of nanoparticle as well as oxygen saturation of blood. Moreover, silver staining of excised tumor tissue confirmed nanoparticle deposition, and showed good correlation with spectroscopic PA images. The results of our study suggest that three-dimensional ultrasound-guided spectroscopic PA imaging can monitor nanoparticle delivery in vivo.
doi:10.1364/BOE.2.002540
PMCID: PMC3184863  PMID: 21991546
(170.5120) Photoacoustic imaging; (110.7170) Ultrasound; (170.3880) Medical and biological imaging
14.  Photoacoustic imaging of prostate brachytherapy seeds 
Biomedical Optics Express  2011;2(8):2243-2254.
Brachytherapy seed therapy is an increasingly common way to treat prostate cancer through localized radiation. The current standard of care relies on transrectal ultrasound (TRUS) for imaging guidance during the seed placement procedure. As visualization of individual metallic seeds tends to be difficult or inaccurate under TRUS guidance, guide needles are generally tracked to infer seed placement. In an effort to improve seed visualization and placement accuracy, the use of photoacoustic (PA) imaging, which is highly sensitive to metallic objects in soft tissue, was investigated for this clinical application. The PA imaging properties of bare (i.e., embedded in pure gelatin) and tissue-embedded (at depths of up to 13 mm) seeds were investigated with a multi-wavelength (750 to 1090 nm) PA imaging technique. Results indicate that, much like ultrasonic (US) imaging, an angular dependence (i.e., seed orientation relative to imaging transducer) of the PA signal exists. Despite this shortcoming, however, PA imaging offers improved contrast, over US imaging, of a seed in prostate tissue if sufficient local fluence is achieved. Additionally, although the PA signal of a bare seed is greatest for lower laser wavelengths (e.g., 750 nm), the scattering that results from tissue tends to favor the use of higher wavelengths (e.g., 1064 nm, which is the primary wavelength of Nd:YAG lasers) when the seed is located in tissue. A combined PA and US imaging approach (i.e., PAUS imaging) shows strong potential to visualize both the seed and the surrounding anatomical environment of the prostate during brachytherapy seed placement procedures.
doi:10.1364/BOE.2.002243
PMCID: PMC3149522  PMID: 21833361
(170.5120) Photoacoustic imaging; (170.7170) Ultrasound; (170.1610) Clinical applications; (170.7230) Urology; (170.3660) Light propagation in tissues; (110.0113) Imaging through turbid media
15.  An Autocorrelation-Based Method for Improvement of Sub-Pixel Displacement Estimation in Ultrasound Strain Imaging 
In ultrasound strain and elasticity imaging, an accurate and cost-effective sub-pixel displacement estimator is required because strain/elasticity imaging quality relies on the displacement SNR, which can often be higher if more computational resources are provided. In this paper, we introduce an autocorrelation-based method to cost-effectively improve sub-pixel displacement estimation quality. To quantitatively evaluate the performance of the autocorrelation method, simulated and tissue-mimicking phantom experiments were performed. The computational cost of the autocorrelation method is also discussed. The results of our study suggest the autocorrelation method can be used for a real-time elasticity imaging system.
doi:10.1109/TUFFC.2011.1876
PMCID: PMC3093758  PMID: 21507761
16.  Utility of biodegradable plasmonic nanoclusters in photoacoustic imaging 
Optics letters  2010;35(22):3751-3753.
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.
PMCID: PMC3071708  PMID: 21081985
17.  Assessment of Shear Modulus of Tissue Using Ultrasound Radiation Force Acting on a Spherical Acoustic Inhomogeneity 
An ultrasound-based method to locally assess the shear modulus of a medium is reported. The proposed approach is based on the application of an impulse acoustic radiation force to an inhomogeneity in the medium and subsequent monitoring of the spatio-temporal response. In our experimental studies, a short pulse produced by a 1.5-MHz highly focused ultrasound transducer was used to initiate the motion of a rigid sphere embedded into an elastic medium. Another 25 MHz focused ultrasound transducer operating in pulse-echo mode was used to track the displacement of the sphere. The experiments were performed in gel phantoms with varying shear modulus to demonstrate the relationship between the displacement of the sphere and shear modulus of the surrounding medium. Because the magnitude of acoustic force applied to sphere depends on the acoustic material properties and, therefore, cannot be used to assess the absolute value of shear modulus, the temporal behavior of the displacement of the sphere was analyzed. The results of this study indicate that there is a strong correlation between the shear modulus of a medium and spatio-temporal characteristics of the motion of the rigid sphere embedded in this medium.
doi:10.1109/TUFFC.2009.1326
PMCID: PMC3059155  PMID: 19942525
18.  Function of mesenchymal stem cells following loading of gold nanotracers 
Background:
Stem cells can differentiate into multiple cell types, and therefore can be used for cellular therapies, including tissue repair. However, the participation of stem cells in tissue repair and neovascularization is not well understood. Therefore, implementing a noninvasive, long-term imaging technique to track stem cells in vivo is needed to obtain a better understanding of the wound healing response. Generally, we are interested in developing an imaging approach to track mesenchymal stem cells (MSCs) in vivo after delivery via a polyethylene glycol modified fibrin matrix (PEGylated fibrin matrix) using MSCs loaded with gold nanoparticles as nanotracers. The objective of the current study was to assess the effects of loading MSCs with gold nanoparticles on cellular function.
Methods:
In this study, we utilized various gold nanoparticle formulations by varying size and surface coatings and assessed the efficiency of cell labeling using darkfield microscopy. We hypothesized that loading cells with gold nanotracers would not significantly alter cell function due to the inert and biocompatible characteristics of gold. The effect of nanoparticle loading on cell viability and cytotoxicity was analyzed using a LIVE/DEAD stain and an MTT assay. The ability of MSCs to differentiate into adipocytes and osteocytes after nanoparticle loading was also examined. In addition, nanoparticle loading and retention over time was assessed using inductively coupled plasma mass spectrometry (ICP-MS).
Conclusion:
Our results demonstrate that loading MSCs with gold nanotracers does not alter cell function and, based on the ICP-MS results, long-term imaging and tracking of MSCs is feasible. These findings strengthen the possibility of imaging MSCs in vivo, such as with optical or photoacoustic imaging, to understand better the participation and role of MSCs in neovascularization.
doi:10.2147/IJN.S16354
PMCID: PMC3075906  PMID: 21499430
neovascularization; gold nanoparticles; cell tracking; stem cells; fibrin gel; optical imaging
19.  Photoacoustics for molecular imaging and therapy 
Physics today  2009;62(8):34-39.
Sound waves generated by light are the basis of a sensitive medical imaging technique with applications to cancer diagnosis and treatment.
PMCID: PMC2879661  PMID: 20523758
20.  Adaptive beamforming for photoacoustic imaging 
Optics letters  2008;33(12):1291-1293.
An adaptive photoacoustic image reconstruction technique that combines coherence factor (CF) weighting and the minimum variance (MV) method is introduced. The backprojection method is widely used to reconstruct photoacoustic tomography images. Owing to the scattering of light, the quality of the photoacoustic imaging can be degraded. CF, an adaptive weighting technique, is known to improve the lateral resolution of photoacoustic images. In addition, an MV adaptive beamforming method can further improve the image quality by suppressing signals from off-axis directions. Experimental studies are performed to quantify the spatial resolution and contrast of the adaptive photoacoustic beamforming methods.
PMCID: PMC2713818  PMID: 18552935
21.  Ultrasound measurements of cavitation bubble radius for femtosecond laser-induced breakdown in water 
Optics letters  2008;33(12):1357-1359.
A recently developed ultrasound technique is evaluated by measuring the behavior of a cavitation bubble that is induced in water by a femtosecond laser pulse. The passive acoustic emission during optical breakdown is used to estimate the location of the cavitation bubble’s origin. In turn, the position of the bubble wall is defined based on the active ultrasonic pulse-echo signal. The results suggest that the developed ultrasound technique can be used for quantitative measurements of femtosecond laser-induced microbubbles.
PMCID: PMC2459242  PMID: 18552957
22.  Quantitative ultrasound method to detect and monitor laser-induced cavitation bubbles 
Journal of biomedical optics  2008;13(3):034011.
An ultrasound technique to measure the spatial and temporal behavior of the laser-induced cavitation bubble is introduced. The cavitation bubbles were formed in water and in gels using a nanosecond pulsed Nd:YAG laser operating at 532 nm. A focused, single-element, 25-MHz ultrasound transducer was employed both to detect the acoustic emission generated by plasma expansion and to acoustically probe the bubble at different stages of its evolution. The arrival time of the passive acoustic emission was used to estimate the location of the cavitation bubble’s origin and the time of flight of the ultrasound pulse-echo signal was used to define its spatial extent. The results of ultrasound estimations of the bubble size were compared and found to be in agreement with both the direct optical measurements of the stationary bubble and the theoretical estimates of bubble dynamics derived from the well-known Rayleigh model of a cavity collapse. The results of this study indicate that the proposed quantitative ultrasound technique, capable of detecting and accurately measuring laser-induced cavitation bubbles in water and in a tissue-like medium, could be used in various biomedical and clinical applications.
doi:10.1117/1.2937478
PMCID: PMC2562569  PMID: 18601556
ultrasonics; shock; emission; laser-induced damage; laser application; lasers in medicine
23.  Remote Temperature Estimation in Intravascular Photoacoustic Imaging 
Ultrasound in medicine & biology  2007;34(2):299-308.
Intravascular photoacoustic (IVPA) imaging is based on the detection of laser-induced acoustic waves generated within the arterial tissue under pulsed laser irradiation. Generally, laser radiant energy levels are kept low (20 mJ/cm2) during photoacoustic imaging to conform to general standards for safe use of lasers on biological tissues. However, safety standards in intravascular photoacoustic imaging are not yet fully established. Consequently, monitoring spatio-temporal temperature changes associated with laser-tissue interaction is important to address thermal safety of IVPA imaging. In this study we utilize the IVUS based strain measurements to estimate the laser induced temperature increase. Temporal changes in temperature were estimated in a phantom modeling a vessel with an inclusion. A cross-correlation based time delay estimator was used to assess temperature induced strains produced by different laser radiant energies. The IVUS based remote measurements revealed temperature increases of 0.7±0.3°C, 2.9±0.2 °C and 5.0±0.2 °C, for the laser radiant energies of 30 mJ/cm2, 60 mJ/cm2 and 85 mJ/cm2 respectively. The technique was then used in imaging of ex vivo samples of a normal rabbit aorta. For arterial tissues, a temperature elevation of 1.1°C was observed for a laser fluence of 60 mJ/cm2 and lesser than 1°C for lower energy levels normally associated with IVPA imaging. Therefore, the developed ultrasound technique can be used to monitor temperature during IVPA imaging. Furthermore, the analysis based on the Arrhenius thermal damage model indicates no thermal injury in the arterial tissue; suggesting the safety of IVPA imaging
doi:10.1016/j.ultrasmedbio.2007.07.021
PMCID: PMC2267933  PMID: 17935861
Atherosclerosis; photoacoustic imaging; laser; vulnerable plaque; coronary artery; intravascular ultrasound; optoacoustic imaging; thermoacoustic imaging; temperature; Arrhenius thermal damage model
24.  Correspondence of Ultrasound Elasticity Imaging to Direct Mechanical Measurement in Aging DVT in Rats 
Ultrasound in medicine & biology  2005;31(10):1351-1359.
Previous ultrasound elasticity imaging experiments supported a generally accepted concept that the hardness of deep venous thrombi increases with thrombus aging. Results also showed that this non-invasive imaging technique can accurately predict thrombus age through strain estimates in a well controlled animal study. In the present study, as an alternative means to characterize elastic properties of thrombi, we employed a direct mechanical measurement system to estimate Young’s modulus of ex vivo thrombi. Unlike conventional indentation tests, the device utilizes a specific compression geometry for cylindrical tissue specimens. We also proposed an approximation scheme to retrieve Young’s modulus from force-displacement measurements made using the device. Finite element simulations and calibrations on tissue-mimicking phantoms validated the system. Then, using two groups of rats with surgically induced thrombi, we further investigated the correlation between Young’s modulus measured ex vivo and elasticity images reconstructed in vivo. This comparison was accomplished by converting the intra-thrombus strains measured in the in vivo studies into Young’s modulus estimates using a model based approach. Good agreement between time-dependent Young’s modulus estimates observed in vivo and direct measurements of Young’s modulus using the mechanical device helps to confirm the ability of elasticity imaging to age DVT for efficient treatment.
doi:10.1016/j.ultrasmedbio.2005.06.005
PMCID: PMC1343482  PMID: 16223638
Deep venous thrombosis; Mechanical measurement; Ultrasound elasticity imaging; Elasticity reconstruction; Young’s modulus
25.  Intravascular Photoacoustic Imaging 
Intravascular photoacoustic (IVPA) imaging is a catheter-based, minimally invasive, imaging modality capable of providing high-resolution optical absorption map of the arterial wall. Integrated with intravascular ultrasound (IVUS) imaging, combined IVPA and IVUS imaging can be used to detect and characterize atherosclerotic plaques building up in the inner lining of an artery. In this paper, we present and discuss various representative applications of combined IVPA/IVUS imaging of atherosclerosis, including assessment of the composition of atherosclerotic plaques, imaging of macrophages within the plaques, and molecular imaging of biomarkers associated with formation and development of plaques. In addition, imaging of coronary artery stents using IVPA and IVUS imaging is demonstrated. Furthermore, the design of an integrated IVUS/IVPA imaging catheter needed for in vivo clinical applications is discussed.
doi:10.1109/JSTQE.2009.2037023
PMCID: PMC3045110  PMID: 21359138
Atherosclerosis; contrast agent; imaging catheter; intravascular photoacoustic (IVPA) imaging; intravascular ultrasound (IVUS) imaging; molecular imaging; stent; vulnerable plaque

Results 1-25 (27)