Sergey A. Ermilov

Laser optoacoustic imaging system for detection of breast cancer

We designed, fabricated and tested the laser optoacoustic imaging system for breast cancer detection (LOIS-64), which fuses optical and acoustic imaging techniques in one modality by utilizing pulsed optical illumination and ultrawide-band ultrasonic detection of resulting optoacoustic (OA) signals. The system was designed to image a single breast slice in craniocaudal or mediolateral projection with an arc-shaped array of 64 ultrawide-band acoustic transducers. The system resolution on breast phantoms was at least 0.5 mm. The single-channel sensitivity of 1.66 mVPa was estimated to be sufficient for single-pulse imaging of 6 to 11 mm tumors through the whole imaging slice of the breast. The implemented signal processing using the wavelet transform allowed significant reduction of the low-frequency (LF) acoustic noise, allowed localization of the optoacoustic signals from tumors, and enhanced the contrast and sharpened the boundaries of the optoacoustic images of the tumors. During the preliminary clinical studies on 27 patients, the LOIS-64 was able to visualize 18 out of 20 malignant lesions suspected from mammography and ultrasound images and confirmed by the biopsy performed after the optoacoustic tomography (OAT) procedure.

Whole-body three-dimensional optoacoustic tomography system for small animals

We develop a system for three-dimensional whole-body optoacoustic tomography of small animals for applications in preclinical research. The tomographic images are obtained while the objects of study (phantoms or mice) are rotated within a sphere outlined by a concave arc-shaped array of 64 piezocomposite transducers. Two pulsed lasers operating in the near-IR spectral range (755 and 1064 nm) with an average pulsed energy of about 100 mJ, a repetition rate of 10 Hz, and a pulse duration of 15 to 75 ns are used as optical illumination sources. During the scan, the mouse is illuminated orthogonally to the array with two wide beams of light from a bifurcated fiber bundle. The system is capable of generating images of individual organs and blood vessels through the entire body of a mouse with spatial resolution of approximately 0.5 mm.

An Imaging Model Incorporating Ultrasonic Transducer Properties for Three-Dimensional Optoacoustic Tomography

Optoacoustic tomography (OAT) is a hybrid imaging modality that combines the advantages of optical and ultrasound imaging. Most existing reconstruction algorithms for OAT assume that the ultrasound transducers employed to record the measurement data are point-like. When transducers with large detecting areas and/or compact measurement geometries are utilized, this assumption can result in conspicuous image blurring and distortions in the reconstructed images. In this work, a new OAT imaging model that incorporates the spatial and temporal responses of an ultrasound transducer is introduced. A discrete form of the imaging model is implemented and its numerical properties are investigated. We demonstrate that use of the imaging model in an iterative reconstruction method can improve the spatial resolution of the optoacoustic images as compared to those reconstructed assuming point-like ultrasound transducers.

Real-time optoacoustic monitoring and three-dimensional mapping of a human arm vasculature

We present our findings from a real-time laser optoacoustic imaging system (LOIS). The system utilizes a Q-switched Nd:YAG laser; a standard 128-channel ultrasonic linear array probe; custom electronics and custom software to collect, process, and display optoacoustic (OA) images at 10 Hz. We propose that this system be used during preoperative mapping of forearm vessels for hemodialysis treatment. To demonstrate the real-time imaging capabilities of the system, we show OA images of forearm vessels in a volunteer and compare our results to ultrasound images of the same region. Our OA images show blood vessels in high contrast. Manipulations with the probe enable us to locate and track arteries and veins of a forearm in real time. We also demonstrate the ability to combine a series of OA image slices into a volume for spatial representation of the vascular network. Finally, we use frame-by-frame analysis of the recorded OA video to measure dynamic changes of the crossection of the ulnar artery.

Development of laser optoacoustic and ultrasonic imaging system for breast cancer utilizing handheld array probes

We describe two laser optoacoustic imaging systems for breast cancer detection based on arrays of acoustic detectors operated manually in a way similar to standard ultrasonic breast imaging. The systems have the advantages of standard light illumination (regardless of the interrogated part of the breast), the ability to visualize any part of the breast, and convenience in operation. The first system could work in both ultrasonic and optoacoustic mode, and was developed based on a linear ultrasonic breast imaging probe with two parallel rectangular optical bundles. We used it in a pilot clinical study to provide for the first time demonstration that the boundaries of the tumors visualized on the optoacoustic and ultrasonic images matched. Such correlation of coregistered images proves that the objects on both images represented indeed the same tumor. In the optoacoustic mode we were also able to visualize blood vessels located in the neighborhood of the tumor. The second system was proposed as a circular array of acoustic transducers with an axisymmetric laser beam in the center. It was capable of 3D optoacoustic imaging with minimized optoacoustic artifacts caused by the distribution of the absorbed optical energy within the breast tissue. The distribution of optical energy absorbed in the bulk tissue of the breast was removed from the image by implementing the principal component analysis on the measured signals. The computer models for optoacoustic imaging using these two handheld probes were developed. The models included three steps: (1) Monte Carlo simulations of the light distribution within the breast tissue, (2) generation of optoacoustic signals by convolving N-shaped pressure signals from spherical voxels with the shape of individual transducers, and (3) back-projecting processed optoacoustic signals onto spherical surfaces for image reconstruction. Using the developed models we demonstrated the importance of the included spatial impulse response of the optoacoustic imaging system.

Combining optical tweezers and patch clamp for studies of cell membrane electromechanics

We have designed and implemented a novel experimental setup which combines optical tweezers with patch-clamp apparatus to investigate the electromechanical properties of cellular plasma membranes. In this system, optical tweezers provide measurement of forces at piconewton scale, and the patch-clamp technique allows control of the cell transmembrane potential. A micron-size bead trapped by the optical tweezers is brought in contact with the membrane of a voltage-clamped cell, and subsequently moved away to form a plasma membrane tether. Bead displacement from the trapping center is monitored by a quadrant photodetector for dynamic measurements of tether force. Fluorescent beads and the corresponding fluorescence imaging optics are used to eliminate the shadow of the cell projected on the quadrant photodetector. Salient information associated with the mechanical properties of the membrane tether can thus be obtained. A unique feature of this setup is that the patch-clamp headstage and the manipulator for the recording pipette are mounted on a piezoelectric stage, preventing relative movements between the cell and the patch pipette during the process of tether pulling. Tethers can be pulled from the cell membrane at different holding potentials, and the tether force response can be measured while changing transmembrane potential. Experimental results from mammalian cochlear outer hair cells and human embryonic kidney cells are presented.

Acoustic signals generated by laser-irradiated metal nanoparticles

We present a physical model that explains several sequential stages of the conversion of optical to acoustical energy when irradiating diluted suspensions of metal nanoparticles with laser pulses. Optical absorption and scattering of a single particle driven by plasmon resonance interactions in an aqueous medium are considered. Thermal effects produced by laser-irradiated nanoparticles, dynamics of vapor bubble formation, and acoustic signals from expanding bubbles formed around heated nanoparticles are calculated. Stochastic features of the pressure magnitude emitted as a result of low-fluence irradiation of suspensions are also discussed. The probabilistic distribution of pressure magnitude from individual bubbles was found to obey Zipfs law for low concentrations of nanoparticles, while increasing their concentration brings the pressure magnitude distribution into conformance with the Gaussian law.

Optoacoustic imaging of the prostate: development toward image-guided biopsy.

Optoacoustic (OA) tomography has demonstrated utility in identifying blood-rich malignancies in breast tissue. We describe the development and characterization of a laser OA imaging system for the prostate (LOIS-P). The system consists of a fiber-coupled Q-switched laser operating at 757 nm, a commercial 128-channel ultrasonic probe, a digital signal processor, and software that uses the filtered radial back-projection algorithm for image reconstruction. The system is used to reconstruct OA images of a blood-rich lesion induced in vivo in a canine prostate. OA images obtained in vivo are compared to images acquired using ultrasound, the current gold standard for guiding biopsy of the prostate. Although key structural features such as the urethra could be identified with both imaging techniques, a bloody lesion representing a highly vascularized tumor could only be clearly identified in OA images. The advantages and limitations of both forward and backward illumination modes are also evaluated by collecting OA images of phantoms simulating blood vessels within tissue. System resolution is estimated to be 0.2 mm in the radial direction of the acoustic array. The minimum detectable pressure signal is 1.83 Pa. Our results encourage further development toward a dual-modality OA/ultrasonic system for prostate imaging and image-guided biopsy.

Three-dimensional optoacoustic imaging as a new noninvasive technique to study long-term biodistribution of optical contrast agents in small animal models

Abstract. We used a 3-D optoacoustic (OA) tomography system to create maps of optical absorbance of mice tissues contrasted with gold nanorods (GNRs). Nude mice were scanned before and after injection of GNRs at time periods varying from 1 to 192 h. Synthesized GNRs were purified from hexadecyltrimethylammonium bromide and coated with polyethylene glycol (PEG) to obtain GNR-PEG complexes suitable for in vivo applications. Intravenous administration of purified GNR-PEG complexes resulted in enhanced OA contrast of internal organs and blood vessels compared to the same mouse before injection of the contrast agent. Maximum enhancement of the OA images was observed 24 to 48 h postinjection, followed by a slow clearance trend for the remaining part of the studied period (eight days). We demonstrate that OA imaging with two laser wavelengths can be used for noninvasive, long-term studies of biological distribution of contrast agents.

Measurement of the spectral directivity of optoacoustic and ultrasonic transducers with a laser ultrasonic source

Comprehensive characterization of wideband ultrasonic transducers and specifically optoacoustic detectors is achieved through the analysis of their frequency response as a function of the incident angle. The tests are performed under well-defined, repeatable operating conditions. Backillumination of a blackened, acoustically matched planar surface with a short laser pulse creates an acoustic impulse which is used as a wideband ultrasonic source. Upon illumination with a short laser pulse, the bandwidth of our source shows a -6 dB point of 12 MHz and a low-frequency roll-off around 300 kHz. Using proprietary software, we examine thoroughly the planarity of the emitted wave front within a specified amplitude cutoff and phase incoherence. Analysis of the angular dependence of the frequency response yields invaluable directivity information about the detector under study: a necessary component toward accurate optoacoustic image reconstruction and quantitative tomography. The laser ultrasonic source we developed is the main feature of our directivity measurement setup. Due to its simplicity, it can easily be adapted to various calibration devices. This paper focuses on the development and characterization of the flatness and the bandwidth of our wideband ultrasonic source.