Russell S. Witte

Microwave-Induced Thermoacoustic Imaging Model for Potential Breast Cancer Detection

In this study, we develop a complete microwave-induced thermoacoustic imaging (TAI) model for potential breast cancer imaging application. Acoustic pressures generated by different breast tissue targets are investigated by finite-difference time-domain simulations of the entire TAI process including the feeding antenna, matching mechanism, fluidic environment, 3-D breast model, and acoustic transducer. Simulation results achieve quantitative relationships between the input microwave peak power and the resulting specific absorption rate as well as the output acoustic pressure. Microwave frequency dependence of the acoustic signals due to different breast tissues is established across a broadband frequency range (2.3-12 GHz), suggesting key advantages of spectroscopic TAI compare to TAI at a single frequency. Reconstructed thermoacoustic images are consistent with the modeling results. This model will contribute to design, optimization, and safety evaluation of microwave-induced TAI and spectroscopy.

Ultrasound Current Source Density Imaging

Surgery to correct severe heart arrhythmias usually requires detailed maps of the cardiac activation wave prior to ablation. The pinpoint electrical mapping procedure is laborious and limited by its spatial resolution (5-10 mm). We propose ultrasound current source density imaging (UCSDI), a direct 3-D imaging technique that potentially facilitates existing mapping procedures with superior spatial resolution. The technique is based on a pressure-induced change in resistivity known as the acoustoelectric (AE) effect, which is spatially confined to the ultrasound focus. AE-modulated voltage recordings are used to map and reconstruct current densities. In this preliminary study, we tested UCSDI under controlled conditions and compared it with conventional electrical mapping techniques. A 2-D dipole field was produced by a pair of electrodes in a bath of 0.9% NaCl solution. Boundary electrodes detected the AE signal while a 7.5-MHz focused ultrasound transducer was scanned across the bath. UCSDI located the current source and sink to within 1 mm of their actual positions. A future UCSDI system potentially provides real-time 3-D images of the cardiac activation wave coregistered with anatomical ultrasound and would greatly facilitate corrective procedures for heart abnormalities.

Self-Organizing Maps

Self-organizing map (SOM) has been applied in many different fields of science and engineering. In this chapter it is shown how the SOM can be used to decode neural spike trains of an awake animal and associate external auditory stimuli with spike patterns of the brain. This chapter begins with an introduction of the SOM and highlights advantages of the SOM when compared to other multivariate statistical data analysis tools commonly used to analyze similar data sets. In this study, simultaneous multichannel recording from guinea pig auditory cortex is examined using the SOM to assess the effectiveness and potential of the SOM in neurophysiological studies.

Real-time photoacoustic and ultrasound imaging: a simple solution for clinical ultrasound systems with linear arrays

Recent clinical studies have demonstrated that photoacoustic imaging (PAI) provides important diagnostic information during a routine breast exam for cancer. PAI enhances contrast between blood vessels and background tissue, which can help characterize suspicious lesions. However, most PAI systems are either not compatible with commercial ultrasound systems or inefficiently deliver light to the region of interest, effectively reducing the sensitivity of the technique. To address and potentially overcome these limitations, we developed an accessory for a standard linear ultrasound array that optimizes light delivery for PAI. The photoacoustic enabling device (PED) exploits an optically transparent acoustic reflector to help direct laser illumination to the region of interest. This study compares the PED with standard fiber bundle illumination in scattering and non-scattering media. In scattering media with the same incident fluence, the PED enhanced the photoacoustic signal by 18 dB at a depth of 5 mm and 6 dB at a depth of 20 mm. To demonstrate in vivo feasibility, we also used the device to image a mouse with a pancreatic tumor. The PED identified blood vessels at the periphery of the tumor, suggesting that PAI provides complementary contrast to standard pulse echo ultrasound. The PED is a simple and inexpensive solution that facilitates the translation of PAI technology to the clinic for routine screening of breast cancer.

Real-time, contrast enhanced photoacoustic imaging of cancer in a mouse window chamber.

A clinical ultrasound scanner and 14 MHz linear array collected real-time photoacoustic images (PAI) during an injection of gold nanorods (GNRs) near the region of a mature PC-3 prostate tumor in mice implanted with a skin flap window chamber. Three dimensional spectroscopic PAI (690-900 nm) was also performed to investigate absorption changes near the tumor and enhance specific detection of GNRs. Whereas GNRs improved PAI contrast (+18 dB), the photoacoustic spectrum was consistent with the elevated near infrared absorption of GNRs. The versatile imaging platform potentially accelerates development of photoacoustic contrast agents and drug delivery for cancer imaging and therapy.

Thin polymer etalon arrays for high-resolution photoacoustic imaging

Thin polymer etalons are demonstrated as high-frequency ultrasound sensors for three-dimensional (3-D) high-resolution photoacoustic imaging. The etalon, a Fabry-Perot optical resonator, consists of a thin polymer slab sandwiched between two gold layers. It is probed with a scanning continuous-wave (CW) laser for ultrasound array detection. Detection bandwidth of a 20-microm-diam array element exceeds 50 MHz, and the ultrasound sensitivity is comparable to polyvinylidene fluoride (PVDF) equivalents of similar size. In a typical photoacoustic imaging setup, a pulsed laser beam illuminates the imaging target, where optical energy is absorbed and acoustic waves are generated through the thermoelastic effect. An ultrasound detection array is formed by scanning the probing laser beam on the etalon surface in either a 1-D or a 2-D configuration, which produces 2-D or 3-D images, respectively. Axial and lateral resolutions have been demonstrated to be better than 20 microm. Detailed characterizations of the optical and acoustical properties of the etalon, as well as photoacoustic imaging results, suggest that thin polymer etalon arrays can be used as ultrasound detectors for 3-D high-resolution photoacoustic imaging applications.

Cardiac activation mapping using ultrasound current source density imaging (UCSDI)

We describe the first mapping of biological current in a live heart using ultrasound current source density imaging (UCSDI). Ablation procedures that treat severe heart arrhythmias require detailed maps of the cardiac activation wave. The conventional procedure is time-consuming and limited by its poor spatial resolution (5-10 mm). UCSDI can potentially improve on existing mapping procedures. It is based on a pressure-induced change in resistivity known as the acousto-electric (AE) effect, which is spatially confined to the ultrasound focus. Data from 2 experiments are presented. A 540 kHz ultrasonic transducer (f/# = 1, focal length = 90 mm, pulse repetition frequency = 1600 Hz) was scanned over an isolated rabbit heart perfused with an excitation-contraction decoupler to reduce motion significantly while retaining electric function. Tungsten electrodes inserted in the left ventricle recorded simultaneously the AE signal and the low-frequency electrocardiogram (ECG). UCSDI displayed spatial and temporal patterns consistent with the spreading activation wave. The propagation velocity estimated from UCSDI was 0.25 plusmn 0.05 mm/ms, comparable to the values obtained with the ECG signals. The maximum AE signal-to-noise ratio after filtering was 18 dB, with an equivalent detection threshold of 0.1 mA/ cm2. This study demonstrates that UCSDI is a potentially powerful technique for mapping current flow and biopotentialsin the heart.

Arterial Vulnerable Plaque Characterization Using Ultrasound-Induced Thermal Strain Imaging (TSI)

Thermal strain imaging (TSI) is demonstrated in two model systems mimicking two potential clinical applications. First, a custom ultrasound (US) microscope produced high-resolution TSI images of an excised porcine coronary artery. Samples were placed in a temperature-controlled water chamber and scanned transversely and longitudinally. Phase-sensitive, correlation-based speckle tracking was applied to map the spatial distribution of temporal strain across the sample. TSI differentiated fatty tissue from water-based arterial wall and muscle with high contrast and a spatial resolution of 60 mum for a 50-MHz transducer. Both transverse and longitudinal TSI images compared well with B-scans of arterial wall structures, including intima, media, adventitia, and overlying fatty tissue. A second model system was used to test the hypothesis that US can produce the heating pattern required for TSI of internal structures. A 2-D phased array with independent drive electronics was combined with a conventional US scanner (iU22, Philips, Bothell, WA) for these studies. This 513-element array, originally designed for the US therapy, acted as the US heat source. To quantify the temporal strain induced by this system, TSI was performed on a homogeneous rubber phantom. TSI temperature estimates were within 3% error for a 3.2degC temperature rise produced within 2 s using a specially designed beamformer and pulse sequencer. The system was then used to produce TSI scanning of an excised kidney containing an intact piece of fat below the collecting system. These images were validated using an magnetic resonance imaging (MRI) pulse sequence designed for lipid quantification. TSI scans matched well MRI scans and histology both anatomically and quantitatively. Finally, to test the potential of US-induced TSI for a significant clinical problem, images were obtained on an excised canine aorta with fatty tissue inside the lumen. Both longitudinal and transversal TSI agreed well with anatomy. These in vitro results demonstrate the potential of high-resolution US-induced TSI with a small temperature change (<1degC) for plaque characterization.

Imaging current flow in lobster nerve cord using the acoustoelectric effect

Ultrasound traversing a biologic fluid or tissue generates a local change in electrical conductivity known as the acoustoelectric effect. The authors exploit this interaction to image ionic current injected into the abdominal segment of the lobster nerve cord. A pair of recording electrodes detected the acoustoelectric signal induced by pulses of focused ultrasound (1.4 or 7.5MHz). The signal was linear with injected current at 2MPa (0.7μV∕mAcm2) and pressure at 75mA∕cm2 (23μV∕MPa). Acoustoelectric imaging of biocurrents potentially enhances spatial resolution of traditional electrophysiology and merits further study as an imaging modality for neural applications.

Identification of vulnerable atherosclerotic plaque using IVUS-based thermal strain imaging

Pathology and autopsy studies have demonstrated that sudden disruption of vulnerable atherosclerotic plaque is responsible for most acute coronary syndromes. These plaques are characterized by a lipid-rich core with abundant inflammatory cells and a thin fibrous cap. Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has been proposed for high-risk arterial plaque detection, in which image contrast results from the temperature dependence of sound speed. It has the potential to distinguish a lipid-laden lesion from the arterial vascular wall due to its strong contrast between water-bearing and lipid-bearing tissue. Initial simulations indicate plaque identification is possible for a 1/spl deg/C temperature rise. A phantom experiment using an IVUS imaging array further supports the concept, and results agree reasonably well with prediction.