Suhyun Park

Photoacoustic imaging and temperature measurement for photothermal cancer therapy.

Photothermal therapy is a noninvasive, targeted, laser-based technique for cancer treatment. During photothermal therapy, light energy is converted to heat by tumor-specific photoabsorbers. The corresponding temperature rise causes localized cancer destruction. For effective treatment, however, the presence of photoabsorbers in the tumor must be ascertained before therapy and thermal imaging must be performed during therapy. This study investigates the feasibility of guiding photothermal therapy by using photoacoustic imaging to detect photoabsorbers and to monitor temperature elevation. Photothermal therapy is carried out by utilizing a continuous wave laser and metal nanocomposites broadly absorbing in the near-infrared optical range. A linear array-based ultrasound imaging system is interfaced with a nanosecond pulsed laser to image tissue-mimicking phantoms and ex-vivo animal tissue before and during photothermal therapy. Before commencing therapy, photoacoustic imaging identifies the presence and spatial location of nanoparticles. Thermal maps are computed by monitoring temperature-induced changes in the photoacoustic signal during the therapeutic procedure and are compared with temperature estimates obtained from ultrasound imaging. The results of our study suggest that photoacoustic imaging, augmented by ultrasound imaging, is a viable candidate to guide photoabsorber-enhanced photothermal therapy.

1E-5 Synergy and Applications of Combined Ultrasound, Elasticity, and Photoacoustic Imaging (Invited)

An advanced in-vivo imaging technology; namely, combined ultrasound, elasticity and photoacoustic imaging, capable of visualizing both structural and functional properties of living tissue, is presented. This hybrid imaging technology is based on the fusion of the complementary imaging modalities and takes full advantage of the many synergistic features of these systems. To highlight fundamental differences and similarities between the imaging systems and to appreciate advantages and limitations of each imaging system, the basic physics of each imaging system is described. The experimental aspects of combined imaging including hardware, signal and image processing algorithms, etc. are presented. Noise and primary artifacts associated with each imaging modality and combined imaging system are analyzed, and techniques to increase and optimize contrast-to-noise and signal-to-noise ratios in the images are discussed. Finally, biomedical and clinical applications of the combined ultrasound, elasticity and photoacoustic imaging ranging from macroscopic to microscopic imaging of pathology are demonstrated and discussed

Adaptive beamforming for photoacoustic imaging

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.

8B-2 Imaging of Iron Oxide Nanoparticles Using Magneto-Motive Ultrasound

Due to its excellent spatial resolution, fast and reliable performance, cost and wide availability, ultrasound should be considered the imaging modality of choice for many applications including molecular imaging. However, ultrasound imaging cannot image molecular content of tissue due to trade-off between spatial resolution and penetration depth. Consequently, contrast agents have been developed both to enhance the contrast of ultrasound images and to make the images molecularly specific. Most ultrasound contrast agents, however, are micrometer sized and may not be applicable to wide range of pathology-specific cellular and molecular imaging. We have developed an imaging technique - magneto-motive ultrasound (MMUS) imaging, capable of imaging magnetic nanoparticles subjected to time-varying magnetic field. The result of our studies indicate that magnetically excited nanoparticles can be used as contrast agents in magneto-motive ultrasound imaging thus expanding the role of ultrasound imaging to cellular scales and molecular sensitivity.

Adaptive beamforming for photoacoustic imaging using linear array transducer

Photoacoustic signals, detected by a transducer array, need to be beamformed for subsequent use in a limited view angle tomography such as B-scan imaging. In the presence of the light scattering or phase aberration, the spatial resolution and contrast in the photoacoustic images are degraded. Phase aberration due to tissues with inhomogeneous acoustic speeds is a major source for image degradation. However, a constant speed of sound (e.g., 1540 m/s) is typically assumed in photoacoustic imaging. Such an assumption can affect the quality of photoacoustic image since changes in sound velocity cause significant phase errors in beamforming. An adaptive weighting method such as coherence factor (CF) technique can improve the ultrasound and photoacoustic image quality significantly. In addition, photoacoustic images can be further improved by applying adaptive beamforming techniques developed for ultrasound imaging. In this study, an adaptive photoacoustic image reconstruction technique that combines an adaptive weighting factor (CF) and an adaptive apodization called minimum variance method (MV) is introduced. Although MV method calculates the optimal apodization weighting factors which minimize the variance of the beamformed signal, it can lead to unexpected weighting factors since it is data dependant. In this case, CF weighting can help to avoid this problem by weighting the output from the MV method based on signal coherence. Simulations were performed to analyze the spatial resolution using a point targets and to demonstrate improvement in phase aberration correction. Numerical studies demonstrated the superior performance of MV adaptive method combined with CF weighting.

Subharmonic Contrast Microbubble Signals for Noninvasive Pressure Estimation under Static and Dynamic Flow Conditions

Our group has proposed the concept of subharmonic aided pressure estimation (SHAPE) utilizing microbubble-based ultrasound contrast agent signals for the noninvasive estimation of hydrostatic blood pressures. An experimental system for in vitro SHAPE was constructed based on two single-element transducers assembled confocally at a 60° angle to each other. Changes in the first, second and subharmonic amplitudes of five different ultrasound contrast agents were measured in vitro at static hydrostatic pressures from 0–186 mmHg, acoustic pressures from 0.35–0.60 MPa peak-to-peak and frequencies of 2.5–6.6 MHz. The most sensitive agent and optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Logiq 9 scanner (GE Healthcare, Milwaukee, WI). This implementation of SHAPE was then tested under dynamic-flow conditions and compared to pressure-catheter measurements. Over the pressure range studied, the first and second harmonic amplitudes reduced approximately 2 dB for all contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 9–14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r2 = 0.98, p < 0.001). Optimal sensitivity was achieved at a transmit frequency of 2.5 MHz and acoustic pressure of 0.35 MPa using Sonazoid (GE Healthcare, Oslo, Norway). A Logiq 9 scanner was modified to implement SHAPE on a convex transducer with a frequency range from 1.5–4.5 MHz and acoustic pressures from 0–3.34 MPa. Results matched the pressure catheter (r2 = 0.87). In conclusion, subharmonic contrast signals are a good indicator of hydrostatic pressure. Out of the five ultrasound contrast agents tested, Sonazoid was the most sensitive for subharmonic pressure estimation. Real-time SHAPE has been implemented on a commercial scanner and offers the possibility of allowing pressures in the heart and elsewhere to be obtained noninvasively.

Simultaneous grayscale and subharmonic ultrasound imaging on a modified commercial scanner

OBJECTIVE To demonstrate the feasibility of simultaneous dual fundamental grayscale and subharmonic imaging on a modified commercial scanner. MOTIVATION The ability to generate signals at half the insonation frequency is exclusive to ultrasound contrast agents (UCA). Thus, subharmonic imaging (SHI; transmitting at f(0) and receiving at f(0)/2) provides improved visualization of UCA within the vasculature via suppression of the surrounding tissue echoes. While this capability has proven useful in a variety of clinical applications, the SHI suppression of surrounding tissue landmarks (which are needed for sonographic navigation) also limits it use as a primary imaging modality. In this paper we present results using a commercial ultrasound scanner modified to allow imaging in both grayscale (f(0)=4.0 MHz) and SHI (f(0)=2.5 MHz, f(0)/2=1.25 MHz) modes in real time. METHODS A Logiq 9 ultrasound scanner (GE Healthcare, Milwaukee, WI) with a 4C curvilinear probe was modified to provide this capability. Four commercially available UCA (Definity, Lantheus Medical Imaging, North Billerica, MA; Optison, GE Healthcare, Princeton, NJ; SonoVue, Bracco Imaging, Milan, Italy; and Sonazoid, GE Healthcare, Oslo, Norway) were all investigated in vitro over an acoustic output range of 3.34 MPa. In vivo the subharmonic response of Sonazoid was investigated in the portal veins of four canines (open abdominal cavity) and four patients with suspected portal hypertension. RESULTS In vitro, the four UCA showed an average maximum subharmonic amplitude of 44.1±5.4 dB above the noise floor with a maximum subharmonic amplitude of 48.6±1.6 dB provided by Sonazoid. The average in vivo maximum signal above the noise floor from Sonazoid was 20.8±2.3 dB in canines and 33.9±5.2 dB in humans. Subharmonic amplitude as a function of acoustic output in both groups matched the S-curve behavior of the agent observed in vitro. The dual grayscale imaging provided easier sonographic navigation, while the degree of tissue suppression in SHI mode varied greatly on a case by case basis. CONCLUSIONS These results demonstrate the feasibility of dual grayscale and SHI on a modified commercial scanner. The ability to simultaneously visualize both imaging modes in real time should improve the applicability of SHI as a future primary clinical imaging modality.

Elasticity Imaging Using Conventional and High-Frame Rate Ultrasound Imaging: Experimental Study

High-frame rate ultrasound imaging is necessary to track fast deformation in ultrasound elasticity imaging, but the image quality may be degraded. Previously, we investigated the performance of strain imaging using numerical models of conventional and ultrafast ultrasound imaging techniques. In this paper, we performed experimental studies to quantitatively evaluate the strain images and elasticity maps obtained using conventional and high frame rate ultrasound imaging methods. The experiments were carried out using point target and tissue mimicking phantoms. The experimental results were compared with the results of numerical simulation. Our experimental studies confirm that the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and axial/lateral resolution of the displacement and strain images acquired using high-frame rate ultrasound imaging are slightly lower but comparable with those obtained using conventional imaging. Furthermore, the quality of elasticity images also exhibits similar trends. Thus, high-frame rate ultrasound imaging can be used reliably for static elasticity imaging to capture the internal tissue motion if the frame rate is critical.

Strain imaging using conventional and ultrafast ultrasound imaging: numerical analysis

In elasticity imaging, the ultrasound frames acquired during tissue deformation are analyzed to estimate the internal displacements and strains. If the deformation rate is high, high-frame-rate imaging techniques are required to avoid the severe decorrelation between the neighboring ultrasound images. In these high-frame-rate techniques, however, the broader and less focused ultrasound beam is transmitted and, hence, the image quality is degraded. We quantitatively compared strain images obtained using conventional and ultrafast ultrasound imaging methods. The performance of the elasticity imaging was evaluated using custom-designed, numerical simulations. Our results demonstrate that signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and spatial resolutions in displacement and strain images acquired using conventional and ultrafast ultrasound imaging are comparable. This study suggests that the high-frame-rate ultrasound imaging can be reliably used in elasticity imaging if frame rate is critical

Three-Dimensional Subharmonic Ultrasound Imaging In Vitro and In Vivo

RATIONALE AND OBJECTIVES Although contrast-enhanced ultrasound imaging techniques such as harmonic imaging (HI) have evolved to reduce tissue signals using the nonlinear properties of the contrast agent, levels of background suppression have been mixed. Subharmonic imaging (SHI) offers near complete tissue suppression by centering the receive bandwidth at half the transmitting frequency. The aims of this study were to demonstrate the feasibility of three-dimensional (3D) SHI and to compare it to 3D HI. MATERIALS AND METHODS Three-dimensional HI and SHI were implemented on a Logiq 9 ultrasound scanner with a 4D10L probe. Four-cycle SHI was implemented to transmit at 5.8 MHz and receive at 2.9 MHz, while two-cycle HI was implemented to transmit at 5 MHz and receive at 10 MHz. The ultrasound contrast agent Definity was imaged within a flow phantom and the lower pole of two canine kidneys in both HI and SHI modes. Contrast-to-tissue ratios and rendered images were compared offline. RESULTS SHI resulted in significant improvement in contrast-to-tissue ratios relative to HI both in vitro (12.11 ± 0.52 vs 2.67 ± 0.77, P< .001) and in vivo (5.74 ± 1.92 vs 2.40 ± 0.48, P = .04). Rendered 3D subharmonic images provided better tissue suppression and a greater overall view of vessels in a flow phantom and canine renal vasculature. CONCLUSIONS The successful implementation of SHI in 3D allows imaging of vascular networks over a heterogeneous sample volume and should improve future diagnostic accuracy. Additionally, 3D SHI provides improved contrast-to-tissue ratios relative to 3D HI.