Ivan Pelivanov

Optoacoustic imaging of absorbing objects in a turbid medium: ultimate sensitivity and application to breast cancer diagnostics

One of the major medical applications of optoacoustic (OA) tomography is in the diagnostics of early-stage breast cancer. A numerical approach was developed to characterize the following parameters of an OA imaging system: resolution, maximum depth at which the tumor can be detected, and image contrast. The parameters of the 64-element focused array transducer were obtained. The results of numerical modeling were compared with known analytical solutions and further validated by phantom experiments. The OA images of a 3 mm piece of bovine liver immersed in diluted milk at various depths were obtained. Based on the results of modeling, a signal filtering algorithm for OA image contrast enhancement has been proposed.

Nonlinear contrast enhancement in photoacoustic molecular imaging with gold nanosphere encapsulated nanoemulsions

A composite contrast agent, a nanoemulsion bead with assembled gold nanospheres at the interface, is proposed to improve the specific contrast of photoacoustic molecular imaging. A phase transition in the beads core is induced by absorption of a nanosecond laser pulse with a fairly low laser fluence (∼3.5 mJ/cm2), creating a transient microbubble through dramatically enhanced thermal expansion. This generates nonlinear photoacoustic signals with more than 10 times larger amplitude compared to that of a linear agent with the same optical absorption. By applying a differential scheme similar to ultrasound pulse inversion, more than 40 dB contrast enhancement is demonstrated with suppression of background signals.

Trapping and Photoacoustic Detection of CTCs at the Single Cell per Milliliter Level with Magneto‐Optical Coupled Nanoparticles

Circulating tumor cells (CTCs) have been reported to correlate most closely with cancer development, and can serve as an important marker for metastatic malignancy, tumor recurrence, and prediction of prognosis and therapeutic effi cacy. Detecting and quantifying CTCs, however, have proven to be challenging due to their low abundance in blood. Based on magneto-optical coupled nanoprobes (made of gold nanorod and iron oxide nanoparticles) and photoacoustic (PA) imaging, we report the development of an enabling technology that can detect CTCs at single cell/mL level. Remarkably, at this low cell concentration, approximately 67% of circulating tumor cells can be captured and imaged with just one pass through the magnetic trapping zone. Compared to the conventional in vitro assays, this technology offers signifi cantly improved sensitivity, because it is inherently compatible with large sample volumes. Compared to more advanced in vivo CTC detection methods, this technology can solve the low throughput problem of optical imaging, and streamline the photoacoustic imaging process by combining magnetic enrichment and digital readout into a single step. Most cancer deaths are caused by metastasis, a process

Focused array transducer for two-dimensional optoacoustic tomography

Optoacoustic (OA) imaging utilizes short laser pulses to create acoustic sources in tissue and time resolved detection of generated pressure profiles for image reconstruction. The ultrasonic transients provide information on the distribution of optical absorption coefficient that can be useful for early cancer diagnostics. In this work a new design of wide-band array transducer is developed and tested. The array consists of 32 focused piezo-elements made of PVDF slabs imposed on a cylindrical surface. A single array element response to an OA signal coming from arbitrarily located point source is investigated theoretically and experimentally. The measured signals correspond well to numerically calculated ones. Focal zone maps of the elements with aperture angles 30 degrees and 60 degrees are presented and discussed; the resolution in direction perpendicular to the imaging plane is determined. Point spread function of the whole array is calculated using experimentally obtained signals from the sources located at different distances from the array. Backprojection algorithm is employed for reconstruction of the optoacoustic images. It is shown that the spatial resolution of the images yielded by the proposed array increases significantly compared to previous transducer designs.

Laser ultrasonic diagnostics of residual stress.

Ultrasonic NDE is one of the most promising methods for non-destructive diagnostics of residual stresses. However the relative change of sound velocity, which is directly proportional to applied stress, is extremely small. An initial stress of 100 MPa produces the result of deltaV/V approximately 10(-4). Therefore measurements must be performed with high precision. The required accuracy can be achieved with laser-exited ultrasonic transients. Radiation from a Nd-YAG laser (pulse duration 7 ns, pulse energy 100 microJ) was absorbed by the surface of the sample. The exited ultrasonic transients resembled the form of laser pulses. A specially designed optoacoustic transducer was used both for the excitation and detecting of the ultrasonic pulses. The wide frequency band of the piezodetector made it possible to achieve the time-of-flight measurements with an accuracy of about 0.5 ns. This technique was used for measuring of plane residual stress in welds and for in-depth testing of subsurface residual stresses in metals. Plane stress distribution for welded metallic plates of different thicknesses (2-8 mm) and the subsurface stress distribution for titanium and nickel alloys were obtained. The results of conventional testing are in good agreement with the laser ultrasonic method.

Real-time integrated photoacoustic and ultrasound (PAUS) imaging system to guide interventional procedures: ex vivo study

Because of depth-dependent light attenuation, bulky, low-repetition-rate lasers are usually used in most photoacoustic (PA) systems to provide sufficient pulse energies to image at depth within the body. However, integrating these lasers with real-time clinical ultrasound (US) scanners has been problematic because of their size and cost. In this paper, an integrated PA/US (PAUS) imaging system is presented operating at frame rates >30 Hz. By employing a portable, low-cost, low-pulse-energy (~2 mJ/pulse), high-repetition-rate (~1 kHz), 1053-nm laser, and a rotating galvo-mirror system enabling rapid laser beam scanning over the imaging area, the approach is demonstrated for potential applications requiring a few centimeters of penetration. In particular, we demonstrate here real-time (30 Hz frame rate) imaging (by combining multiple single-shot sub-images covering the scan region) of an 18-gauge needle inserted into a piece of chicken breast with subsequent delivery of an absorptive agent at more than 1-cm depth to mimic PAUS guidance of an interventional procedure. A signal-to-noise ratio of more than 35 dB is obtained for the needle in an imaging area 2.8 × 2.8 cm (depth × lateral). Higher frame rate operation is envisioned with an optimized scanning scheme.

Sono-photoacoustic imaging of gold nanoemulsions: Part I. Exposure thresholds

Integrating high contrast bubbles from ultrasound imaging with plasmonic absorbers from photoacoustic imaging is investigated. Nanoemulsion beads coated with gold nanopsheres (NEB-GNS) are excited with simultaneous light (transient heat at the GNSs) and ultrasound (rarefactional pressure) resulting in a phase transition achievable under different scenarios, enhancing laser-induced acoustic signals and enabling specific detection of nanoprobes at lower concentration. An automated platform allowed dual parameter scans of both pressure and laser fluence while recording broadband acoustic signals. Two types of NEB-GNS and individual GNS were investigated and showed the great potential of this technique to enhance photoacoustic/acoustic signals. The NEB-GNS size distribution influences vaporization thresholds which can be reached at both permissible ultrasound and light exposures at deep penetration and at low concentrations of targets. This technique, called sono-photoacoustics, has great potential for targeted molecular imaging and therapy using compact nanoprobes with potentially high-penetrability into tissue.

Laser-induced cavitation in nanoemulsion with gold nanospheres for blood clot disruption: in vitro results

Optically activated cavitation in a nanoemulsion contrast agent is proposed for therapeutic applications. With a 56°C boiling point perfluorohexane core and highly absorptive gold nanospheres at the oil-water interface, cavitation nuclei in the core can be efficiently induced with a laser fluence below medical safety limits (70 mJ/cm2 at 1064 nm). This agent is also sensitive to ultrasound (US) exposure and can induce inertial cavitation at a pressure within the medical diagnostic range. Images from a high-speed camera demonstrate bubble formation in these nanoemulsions. The potential of using this contrast agent for blood clot disruption is demonstrated in an in vitro study. The possibility of simultaneous laser and US excitation to reduce the cavitation threshold for therapeutic applications is also discussed.

Temperature dependence of the optoacoustic transformation efficiency in ex vivo tissues for application in monitoring thermal therapies

The calibration dependencies of the optoacoustic (OA) transformation efficiency on tissue temperature are obtained for the application in OA temperature monitoring during thermal therapies. Accurate measurement of the OA signal amplitude versus temperature is performed in different ex vivo tissues in the temperature range 25°C to 80°C. The investigated tissues were selected to represent different structural components: chicken breast (skeletal muscle), porcine lard (fatty tissue), and porcine liver (richly perfused tissue). Backward mode of the OA signal detection and a narrow probe laser beam were used in the experiments to avoid the influence of changes in light scattering with tissue coagulation on the OA signal amplitude. Measurements were performed in heating and cooling regimes. Characteristic behavior of the OA signal amplitude temperature dependences in different temperature ranges were described in terms of changes in different structural components of the tissue samples. The accuracy of temperature reconstruction from the obtained calibration dependencies for the investigated tissue types is evaluated.

Thickness Measurement for Submicron Metallic Coatings on a Transparent Substrate by Laser Optoacoustic Technique

A new nondestructive technique for determining the thicknesses of submicron metallic coatings on transparent substrates is developed. The technique is based on measuring the frequency dependence of the efficiency of thermooptical conversion on the thickness of a metallic film in the case of its contact with a transparent fluid. Experiments were conducted with three chromium coatings of different thicknesses (0.2, 0.3, and 0.6 μm) on quartz substrates. Two different experimental schemes were used: a direct scheme (laser radiation hits the film from the side of the substrate) and an indirect one (the laser action upon the film occurs from the side of the fluid). The film thickness is determined by approximating the experimental frequency dependences of thermooptical conversion efficiency by theoretical curves with the use of the least-squares method. The optoacoustic method can be used for determination of coating thicknesses in the range from 50 nm to 5 μm with an error of about 50 nm.