Papers by Andrei Karpiouk
Journal of Biomedical Optics, Sep 6, 2012
Pilot studies of in vivo combined intravascular ultrasound (IVUS) and intravascular photoacoustic... more Pilot studies of in vivo combined intravascular ultrasound (IVUS) and intravascular photoacoustic (IVPA) imaging are reported. A recently introduced prototype of an integrated IVUS/IVPA imaging catheter consisting of a single-element ultrasound transducer and a light delivery system based on a single optical fiber was adapted and used for in vivo imaging of a coronary stent deployed in a rabbit's thoracic aorta in the presence of luminal blood. The results suggest that in vivo IVUS/IVPA imaging is feasible using the integrated IVUS/IVPA imaging catheter. The challenges of in vivo combined IVUS/IVPA imaging are discussed, and further improvements on the design of the catheter and the clinical imaging system are proposed.
Combined ultrasound and photoacoustic imaging

Proceedings of SPIE, Feb 12, 2009
Coronary atherosclerosis is a complex disease accompanied by the development of plaques in the ar... more Coronary atherosclerosis is a complex disease accompanied by the development of plaques in the arterial wall. Since the vulnerability of the plaques depends on their composition, the appropriate treatment of the arteriosclerosis requires a reliable characterization of the plaques' geometry and content. The intravascular ultrasound (IVUS) imaging is capable of providing structural details of the plaques as well as some functional information. In turn, more functional information about the same plaques can be obtained from intravascular photoacoustic (IVPA) images since the optical properties of the plaque's components differ from that of their environment. The combined IVUS/IVPA imaging is capable of simultaneously detecting and differentiating the plaques, thus determining their vulnerability. The potential of combined IVUS/IVPA imaging has already been demonstrated in phantoms and ex-vivo experiments. However, for in-vivo or clinical imaging, an integrated IVUS/IVPA catheter is required. In this paper, we introduce two prototypes of integrated IVUS/IVPA catheters for in-vivo imaging based on a commercially available single-element IVUS imaging catheter. The light delivery systems are developed using multimode optical fibers with custom-designed distal tips. Both prototypes were tested and compared using an arterial mimicking phantom. The advantages and limitations of both designs are discussed. Overall, the results of our studies suggest that both designs of integrated IVUS/IVPA catheter have a potential for in-vivo IVPA/IVUS imaging of atherosclerotic plaques.

Biomedical Optics Express, Jul 12, 2011
Brachytherapy seed therapy is an increasingly common way to treat prostate cancer through localiz... more 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.

Journal of Biomedical Optics, 2008
Treatment of deep venous thrombosis ͑DVT͒-a primary cause of potentially fatal pulmonary embolism... more Treatment of deep venous thrombosis ͑DVT͒-a primary cause of potentially fatal pulmonary embolism ͑PE͒-depends on the age of the thrombus. The existing clinical imaging methods are capable of visualizing a thrombus but cannot determine the age of the blood clot. Therefore, there is a need for an imaging technique to reliably diagnose and adequately stage DVT. To stage DVT ͑i.e., to determine the age of the thrombus, and therefore, to differentiate acute from chronic DVT͒, we explored photoacoustic imaging, a technique capable of noninvasive measurements of the optical absorption in tissue. Indeed, optical absorption of the blood clot changes with age, since maturation of DVT is associated with significant cellular and molecular reorganization. The ultrasound and photoacoustic imaging studies were performed using DVT-mimicking phantoms and phantoms with embedded acute and chronic thrombi obtained from an animal model of DVT. The location and structure of the clots were visualized using ultrasound imaging, while the composition, and therefore age, of thrombi were related to the magnitude and spatiotemporal characteristics of the photoacoustic signal. Overall, the results of our study suggest that combined ultrasound and photoacoustic imaging of thrombi may be capable of simultaneous detection and staging of DVT.

Biomedical Optics Express, Aug 29, 2018
A major obstacle in the monitoring and treatment of neurological diseases is the blood brain barr... more A major obstacle in the monitoring and treatment of neurological diseases is the blood brain barrier (BBB), a semipermeable barrier that prevents the delivery of many therapeutics and imaging contrast agents to the brain. In this work, we explored the possibility of laser-activated perfluorocarbon nanodroplets (PFCnDs) to open the BBB and deliver agents to the brain tissue. Specifically, near infrared (NIR) dye-loaded PFCnDs comprised of a perfluorocarbon (PFC) core with a boiling point above physiological temperature were repeatedly vaporized and recondensed from liquid droplet to gas bubble under pulsed laser excitation. As a result, this pulse-to-pulse repeated behavior enabled the recurring interaction of PFCnDs with the endothelial lining of the BBB, allowing for a BBB opening and extravasation of dye into the brain tissue. The blood brain barrier opening and delivery of agents to tissue was confirmed on the macro and the molecular level by evaluating Evans Blue staining, ultrasound-guided photoacoustic (USPA) imaging, and histological tissue analysis. The demonstrated PFCnD-assisted pulsed laser method for BBB opening, therefore, represents a tool that has the potential to enable non-invasive, cost-effective, and efficient image-guided delivery of contrast and therapeutic agents to the brain.

The goal of this study was to investigate the dynamic behavior of a rigid sphere in viscoelastic ... more The goal of this study was to investigate the dynamic behavior of a rigid sphere in viscoelastic medium in response to the impulsive acoustic radiation force. Theoretical and numerical studies were carried out first. Then, to verify our theoretical and numerical models, the experiments were performed using rigid spheres of various diameters and densities embedded into tissue-like gel-based phantoms of varying mechanical properties. A 1.5 MHz single-element focused transducer was used to apply the desired radiation force. Another single-element focused transducer operating at 25 MHz was used to track the displacements of the sphere. The results of this study demonstrate good agreement between theoretical predictions and experimental measurements. The developed theoretical model accurately describes the displacement of the solid spheres in viscoelastic medium in response to the acoustic radiation force and thus can be used to evaluate mechanical properties of tissue.
Nanoparticle-augmented ultrasound and photoacoustic imaging to track stem cells in the anterior eye
Investigative Ophthalmology & Visual Science, Jul 22, 2019

Journal of Biomedical Optics, Oct 27, 2018
Accurate measurements of microelastic properties of soft tissues in-vivo using optical coherence ... more Accurate measurements of microelastic properties of soft tissues in-vivo using optical coherence elastography can be affected by motion artifacts caused by cardiac and respiratory cycles. This problem can be overcome using a multielement ultrasound transducer probe where each ultrasound transducer is capable of generating acoustic radiation force (ARF) and, therefore, creating shear waves in tissue. These shear waves, produced during the phase of cardiac and respiratory cycles when tissues are effectively stationary, are detected at the same observation point using phase-sensitive optical coherence tomography (psOCT). Given the known distance between the ultrasound transducers, the speed of shear wave propagation can be calculated by measuring the difference between arrival times of shear waves. The combined multitransducer ARF/psOCT probe has been designed and tested in phantoms and ex-vivo studies using fresh rabbit heart. The measured values of shear moduli are in good agreement with those reported in literature. Our results suggest that the developed multitransducer ARF/psOCT probe can be useful for many in-vivo applications, including quantifying the microelasticity of cardiac muscle.

Proceedings of SPIE, Feb 12, 2009
Current biomedical imaging tools have limitations in accurate assessment of the severity of open ... more Current biomedical imaging tools have limitations in accurate assessment of the severity of open and deep burn wounds involving excess bleeding and severe tissue damage. Furthermore, sophisticated imaging techniques are needed for advanced therapeutic approaches such as noninvasive monitoring of stem cells seeded and applied in a biomedical 3D scaffold to enhance wound repair. This work introduces a novel application of combined ultrasound (US) and photoacoustic (PA) imaging to assess both burn injury and skin tissue regeneration. Tissue structural damage and bleeding throughout the epidermis and dermis till the subcutaneous skin layer were imaged noninvasively by US/PA imaging. Gold nanoparticle-labeled adipose-derived stem cells (ASCs) within a PEGylated fibrin 3D gel were implanted in a rat model of cutaneous burn injury. ASCs were successfully tracked till 2 weeks and were distinguished from host tissue components (e.g., epidermis, fat, and blood vessels) through spectroscopic PA imaging. The structure and function of blood vessels (vessel density and perfusion) in the wound bed undergoing skin tissue regeneration were monitored both qualitatively and semi-quantitatively by the developed imaging approach. Imaging-based analysis demonstrated ASC localization in the top layer of skin and a higher density of regenerating blood vessels in the treated groups. This was corroborated with histological analysis showing localization of fluorescently labeled ASCs and smooth muscle alpha actinpositive blood vessels. Overall, the US/PA imaging-based strategy coupled with gold nanoparticles has a great potential for stem cell therapies and tissue engineering due to its noninvasiveness, safety, selectivity, and ability to provide long-term monitoring. Departments of 1 Electrical and Computer Engineering and
IEEE Photonics Journal, 2021
Laser photoacoustic detection of oil hydrocarbons in water emulsions
Laser Physics, 2001
It was found experimentally that the proportionality between photoacoustic response magnitude and... more It was found experimentally that the proportionality between photoacoustic response magnitude and crude oil emulsion concentrations may be lost in natural conditions. In order to understand it the affect of sound velocity, sound attenuation and absorption coefficients of crude oil and water on photoacoustic response were cleaned up. It was found that the light scattering plays an unexpectedly sufficient role in photoacoustic response forming. It has been shown that this problem can be solved by the choice of excitation conditions. The method of selective crude oil (and oil products) detection (1-1500 ppms) in natural water has been proposed.

IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 2016
Combined intravascular ultrasound and photoacoustic imaging (IVUS/IVPA) is an emerging hybrid mod... more Combined intravascular ultrasound and photoacoustic imaging (IVUS/IVPA) is an emerging hybrid modality being explored as a means of improving the characterization of atherosclerotic plaque anatomical and compositional features. While initial demonstrations of the technique have been encouraging, they have been limited by catheter rotation and data acquisition, displaying and processing rates on the order of several seconds per frame as well as the use of off-line image processing. Herein, we present a complete IVUS/IVPA imaging system and method capable of real-time IVUS/IVPA imaging, with online data acquisition, image processing and display of both IVUS and IVPA images. The integrated IVUS/IVPA catheter is fully contained within a 1 mm outer diameter torque cable coupled on the proximal end to a custom-designed spindle enabling optical and electrical coupling to system hardware, including a nanosecond-pulsed laser with a controllable pulse repetition frequency capable of greater than 10kHz, motor and servo drive, an ultrasound pulser/receiver, and a 200 MHz digitizer. The system performance is characterized and demonstrated on a vessel-mimicking phantom with an embedded coronary stent intended to provide IVPA contrast within content of an IVUS image.

Optical coherent elastography method for stiffness assessment of heart muscle tissues (Conference Presentation)
Many complex diseases such as diastolic dysfunction and some types of cardiomyopathy are often ch... more Many complex diseases such as diastolic dysfunction and some types of cardiomyopathy are often characterized by an increased stiffness of heart muscles which can potentially cause heart failure. While changes of heart muscle’s geometry could be detected by various imaging methods, non-invasive measurements of stiffness of the heart muscle are desired to assess such areas of the heart tissues without invasive surgery. A novel minimally-invasive method of stiffness assessment of heart muscle – optical coherent elastography (OCE) – is based on a combination of applied acoustic radiation force for mechanical excitation of tissue with subsequent phase-sensitive optical coherence tomography (psOCT) measurements of spatio-temporal response of tissue. A minimally invasive probe comprising a small, 2x2 mm size, low-frequency (<5MHz) ultrasound transducer and a clinically approved psOCT imaging fiber was incorporated into a single housing such that psOCT beam and acoustic excitation beam w...

Dual-Illumination Ultrasound/Photoacoustic Endoscopic System
2020 IEEE International Ultrasonics Symposium (IUS), 2020
The high mortality rate of cervical cancer can be minimized by early-stage cancer detection or pr... more The high mortality rate of cervical cancer can be minimized by early-stage cancer detection or providing functional information about the tissue to provide an effective treatment. Such clinical procedures require the need for a safe, low-cost, and high-resolution functional diagnostic system. Previously, we proposed a dual-modal ultrasound and photoacoustic imaging endoscope with a miniaturized footprint for imaging the cervical tissue through the cervical canal. Since the light delivery system in our endoscope can carry a limited amount of light fluence (restricted to ANSI safety limits), we proposed to develop a dual, co-planar illumination system to irradiate cervical tissue both from inside and outside. The proposed endoscopic system was developed by coupling the external illumination system to the developed US/PA imaging endoscope. The external illumination system can provide additional illumination to the cervical tissue through the vaginal fornix area. The total diameter of t...

Laser-activated perfluorocarbon nanodroplets as a new tool for image-guided blood brain barrier opening and delivery of imaging/therapeutic agents to the brain
2017 IEEE International Ultrasonics Symposium (IUS), 2017
Perfluorocarbon nanodroplets (PFCnDs) are a tool used in ultrasound (US) as a contrast agent and ... more Perfluorocarbon nanodroplets (PFCnDs) are a tool used in ultrasound (US) as a contrast agent and therapeutic delivery vehicle. When loaded with a photoabsorber, PFCnDs can also provide photoacoustic (PA) contrast, as they undergo a laser-triggered phase change from droplet to bubble. Utilizing this phase-changing behavior, we have investigated the ability of laser-activated PFCnDs to open the blood brain barrier (BBB) and deliver an encapsulated photoabsorber across the BBB. This method of BBB opening could enable non-invasive delivery of contrast or therapeutics to the brain tissue under US/PA image guidance, resulting in a safe, efficient, and cost-effective approach to studying neurological diseases.
Determining the laser damage threshold of tissues for the design of a clinical IVPA imaging protocol
2017 IEEE International Ultrasonics Symposium (IUS), 2017
Depth-resolved intravascular photoacoustic imaging has been shown to successfully image lipid in ... more Depth-resolved intravascular photoacoustic imaging has been shown to successfully image lipid in atherosclerotic plaques. During IVPA imaging, the level of laser irradiation and corresponding thermal dose depends on the imaging parameters (number of A-lines per frame, frame rate, pullback speed, pulse energy). It is unclear what level of laser irradiation will cause inadvertent tissue damage — the laser safety of IVPA imaging in relationship to imaging parameters has not been demonstrated. We investigated the safety of IVPA imaging by ascertaining the threshold beyond which tissue damage occurs. This will determine how parameters of IVPA imaging can be varied in order to achieve optimal image quality without damaging tissue.
Laser photoacoustic control of water quality
Laser Physics, 2001
Photoacoustic response in liquids after pulsed laser excitation usually has a complicated shape w... more Photoacoustic response in liquids after pulsed laser excitation usually has a complicated shape which cannot be explained in simple macroscopic description. It was found experimentally that spatial organization of absorbing analyte can affect on Fourier spectrum of photoacoustic response. It was supposed that the presence of non-absorbing ions in aqueous solution can also affect on photoacoustic response due to water molecules association. It was found in experiments that there is strong correlation between Raman scattering intensity of red part of OH vibrational line (connected with associated molecules) and high-frequency part of photoacoustic Fourier spectrum.
Laser photoacoustic probe of absorber spatial organization
Laser Physics, 2001
It was experimentally found that the Fourier spectra of acoustic responses (in pulsed laser photo... more It was experimentally found that the Fourier spectra of acoustic responses (in pulsed laser photoa-coustics) are different for emulsified and dissolved absorbers. The role of surface sound waves, acoustic dispersion, experimental geometry and macroscopic parameters (e.g., sound velocity, attenuation, thermal expansion etc.) has been cleared up in control experiment. It has been shown that all these parameters cannot explain the difference in Fourier spectra. Simple model of this phenomenon has been proposed and tested in experiment.
Elasticity Imaging and Sensing Using Targeted Motion: From Macro to Nano
Current Medical Imaging Reviews, Feb 1, 2012
Abstract: The methods used to estimate tissue elasticity based on the motion of local inhomogenei... more Abstract: The methods used to estimate tissue elasticity based on the motion of local inhomogeneities such as laser-induced gas microbubbles, magnetic nanoparticles and other targets under an externally applied force are reviewed. The theoretical bases of the motion of a target in a viscoelastic medium are described. Given various targets differing in size, these methods allow for elasticity measurements at different levels of spatial resolution. Short acoustic radiation force and magnetic field pulses were used to initiate the motion of ...
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Papers by Andrei Karpiouk