@article{wang_martin_huang_dayton_jiang_2017, title={Contrast Enhanced Superharmonic Imaging for Acoustic Angiography Using Reduced Form-Factor Lateral Mode Transmitters for Intravascular and Intracavity Applications}, volume={64}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2016.2619687}, abstractNote={Techniques to image the microvasculature may play an important role in imaging tumor-related angiogenesis and vasa vasorum associated with vulnerable atherosclerotic plaques. However, the microvasculature associated with these pathologies is difficult to detect using traditional B-mode ultrasound or even harmonic imaging due to small vessel size and poor differentiation from surrounding tissue. Acoustic angiography, a microvascular imaging technique that utilizes superharmonic imaging (detection of higher order harmonics of microbubble response), can yield a much higher contrast-to-tissue ratio than second harmonic imaging methods. In this paper, two dual-frequency transducers using lateral mode transmitters were developed for superharmonic detection and acoustic angiography imaging in intracavity applications. A single element dual-frequency intravascular ultrasound transducer was developed for concept validation, which achieved larger signal amplitude, better contrast-to-noise ratio (CNR), and pulselength compared to the previous work. A dual-frequency [Pb(Mg<sub>1/3</sub>Nb<sub>2/3</sub>)O<sub>3</sub>]–x[PbTiO<sub>3</sub>] array transducer was then developed for superharmonic imaging with dynamic focusing. The axial and lateral sizes of the microbubbles in a 200-<inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> tube were measured to be 269 and <inline-formula> <tex-math notation="LaTeX">$200~\mu \text{m}$ </tex-math></inline-formula>, respectively. The maximum CNR was calculated to be 22 dB. These results show that superharmonic imaging with a low frequency lateral mode transmitter is a feasible alternative to thickness mode transmitters when the final transducer size requirements dictate design choices.}, number={2}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Wang, Zhuochen and Martin, K. Heath and Huang, Wenbin and Dayton, Paul A. and Jiang, Xiaoning}, year={2017}, month={Feb}, pages={311–319} }
 @article{lindsey_shelton_martin_ozgun_rojas_foster_dayton_2017, title={High Resolution Ultrasound Superharmonic Perfusion Imaging: In Vivo Feasibility and Quantification of Dynamic Contrast-Enhanced Acoustic Angiography}, volume={45}, ISSN={["1573-9686"]}, url={https://europepmc.org/articles/PMC5682933}, DOI={10.1007/s10439-016-1753-9}, abstractNote={Mapping blood perfusion quantitatively allows localization of abnormal physiology and can improve understanding of disease progression. Dynamic contrast-enhanced ultrasound is a low-cost, real-time technique for imaging perfusion dynamics with microbubble contrast agents. Previously, we have demonstrated another contrast agent-specific ultrasound imaging technique, acoustic angiography, which forms static anatomical images of the superharmonic signal produced by microbubbles. In this work, we seek to determine whether acoustic angiography can be utilized for high resolution perfusion imaging in vivo by examining the effect of acquisition rate on superharmonic imaging at low flow rates and demonstrating the feasibility of dynamic contrast-enhanced superharmonic perfusion imaging for the first time. Results in the chorioallantoic membrane model indicate that frame rate and frame averaging do not affect the measured diameter of individual vessels observed, but that frame rate does influence the detection of vessels near and below the resolution limit. The highest number of resolvable vessels was observed at an intermediate frame rate of 3 Hz using a mechanically-steered prototype transducer. We also demonstrate the feasibility of quantitatively mapping perfusion rate in 2D in a mouse model with spatial resolution of ~100 μm. This type of imaging could provide non-invasive, high resolution quantification of microvascular function at penetration depths of several centimeters.}, number={4}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Lindsey, Brooks D. and Shelton, Sarah E. and Martin, K. Heath and Ozgun, Kathryn A. and Rojas, Juan D. and Foster, F. Stuart and Dayton, Paul A.}, year={2017}, month={Apr}, pages={939–948} }
 @article{lindsey_martin_jiang_dayton_2016, title={Adaptive windowing in contrast-enhanced intravascular ultrasound imaging}, volume={70}, ISSN={["1874-9968"]}, DOI={10.1016/j.ultras.2016.04.022}, abstractNote={Intravascular ultrasound (IVUS) is one of the most commonly-used interventional imaging techniques and has seen recent innovations which attempt to characterize the risk posed by atherosclerotic plaques. One such development is the use of microbubble contrast agents to image vasa vasorum, fine vessels which supply oxygen and nutrients to the walls of coronary arteries and typically have diameters less than 200μm. The degree of vasa vasorum neovascularization within plaques is positively correlated with plaque vulnerability. Having recently presented a prototype dual-frequency transducer for contrast agent-specific intravascular imaging, here we describe signal processing approaches based on minimum variance (MV) beamforming and the phase coherence factor (PCF) for improving the spatial resolution and contrast-to-tissue ratio (CTR) in IVUS imaging. These approaches are examined through simulations, phantom studies, ex vivo studies in porcine arteries, and in vivo studies in chicken embryos. In phantom studies, PCF processing improved CTR by a mean of 4.2dB, while combined MV and PCF processing improved spatial resolution by 41.7%. Improvements of 2.2dB in CTR and 37.2% in resolution were observed in vivo. Applying these processing strategies can enhance image quality in conventional B-mode IVUS or in contrast-enhanced IVUS, where signal-to-noise ratio is relatively low and resolution is at a premium.}, journal={ULTRASONICS}, author={Lindsey, Brooks D. and Martin, K. Heath and Jiang, Xiaoning and Dayton, Paul A.}, year={2016}, month={Aug}, pages={123–135} }
 @article{li_ma_martin_yu_ma_dayton_jiang_shung_zhou_2016, title={An Integrated System for Superharmonic Contrast-Enhanced Ultrasound Imaging: Design and Intravascular Phantom Imaging Study}, volume={63}, ISSN={["1558-2531"]}, DOI={10.1109/tbme.2015.2506639}, abstractNote={Objective: Superharmonic contrast-enhanced ultrasound imaging, also called acoustic angiography, has previously been used for the imaging of microvasculature. This approach excites microbubble contrast agents near their resonance frequency and receives echoes at nonoverlapping superharmonic bandwidths. No integrated system currently exists could fully support this application. To fulfill this need, an integrated dual-channel transmit/receive system for superharmonic imaging was designed, built, and characterized experimentally. Method: The system was uniquely designed for superharmonic imaging and high-resolution B-mode imaging. A complete ultrasound system including a pulse generator, a data acquisition unit, and a signal processing unit were integrated into a single package. The system was controlled by a field-programmable gate array, on which multiple user-defined modes were implemented. A 6-, 35-MHz dual-frequency dual-element intravascular ultrasound transducer was designed and used for imaging. Result: The system successfully obtained high-resolution B-mode images of coronary artery ex vivo with 45-dB dynamic range. The system was capable of acquiring in vitro superharmonic images of a vasa vasorum mimicking phantom with 30-dB contrast. It could detect a contrast agent filled tissue mimicking tube of 200 μm diameter. Conclusion: For the first time, high-resolution B-mode images and superharmonic images were obtained in an intravascular phantom, made possible by the dedicated integrated system proposed. The system greatly reduced the cost and complexity of the superharmonic imaging intended for preclinical study. Significant: The system showed promise for high-contrast intravascular microvascular imaging, which may have significant importance in assessment of the vasa vasorum associated with atherosclerotic plaques.}, number={9}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Li, Yang and Ma, Jianguo and Martin, K. Heath and Yu, Mingyue and Ma, Teng and Dayton, Paul A. and Jiang, Xiaoning and Shung, K. Kirk and Zhou, Qifa}, year={2016}, month={Sep}, pages={1933–1943} }
 @article{wang_ma_jiang_martin_dayton_2014, title={An array transmitter for dual-frequency contrast enhanced intravascular ultrasound imaging}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0524}, abstractNote={Recent studies suggests that contrast ultrasound for molecular imaging or vasa vasorum (VV) assessment may be promising in identification of vulnerable plaques. However, conventional intravascular ultrasound (IVUS) transducers with frequency of 15 MHz - 60 MHz are not optimized for imaging with micro bubble contrast agents due to the ineffective micro bubble excitation at high frequencies and poor signal separation from tissue. This paper presents design and fabrication of a lateral mode transducer array with center frequency of 2 MHz for contrast enhanced IVUS (CE-IVUS) imaging, which can generate sufficient pressure to excite microbubbles more effectively and therefore could be used for dual-frequency microbubble superharmonic imaging, or `acoustic angiography'. Several commercial transducers with central frequency of 15 MHz, 20 MHz and 25 MHz were used as receivers to receive the contrast signal. In the contrast testing, the high frequency echo of the nonlinear response from microbubbles in a micro-tube with diameter of 0.2 mm was detected. The maximum contrast to noise ratio was 12.2 dB. The results show that superharmonic signals (over 9th harmonic) can be received; suggesting good resolution and signal separation in contrast enhanced IVUS imaging.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Wang, Zhuochen and Ma, Jianguo and Jiang, Xiaoning and Martin, Karl Heath and Dayton, Paul A.}, year={2014}, pages={2104–2107} }
 @misc{martin_lindsey_ma_lee_li_foster_jiang_dayton_2014, title={Dual-Frequency Piezoelectric Transducers for Contrast Enhanced Ultrasound Imaging}, volume={14}, ISSN={["1424-8220"]}, DOI={10.3390/s141120825}, abstractNote={For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed.}, number={11}, journal={SENSORS}, author={Martin, K. Heath and Lindsey, Brooks D. and Ma, Jianguo and Lee, Mike and Li, Sibo and Foster, F. Stuart and Jiang, Xiaoning and Dayton, Paul A.}, year={2014}, month={Nov}, pages={20825–20842} }
 @article{lindsey_rojas_martin_shelton_dayton_2014, title={Optimization of Contrast-to-tissue Ratio and Role of Bubble Destruction in Dual-Frequency Contrast-Specific "Acoustic Angiography" Imaging}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0440}, abstractNote={Recently, dual-frequency transducers have enabled high-spatial resolution, high-contrast imaging of microvasculature by transmitting at a low frequency and receiving broadband superharmonic echoes from microbubble contrast agents at a higher frequency. In this work, we examine the imaging parameters for optimizing contrast-to-tissue ratio (CTR) for dual-frequency imaging and the relationship between bubble destruction and broadband harmonic signal production. CTR was assessed in vitro by acquiring scattered echoes by bubbles and beef muscle for transmit pressures up to 2 MPa, transmit frequencies from 1.5-8 MHz, and receive frequencies from 7.5 to 25 MHz. Optimum CTR (25.5 dB) was found to occur at the lowest transmit frequencies, though a broad peak exists within the 1.5-3.5 MHz range. At these frequencies, CTR is optimized when receiving at a center frequency of 10 - 15 MHz. A 4 μm-diameter microbubble population yielded ~5 dB higher CTR than a 1 μm population. Single bubble behavior was assessed with simultaneous acoustic and optical recordings. For n=250 single bubbles subjected to five consecutive single-cycle pulses (100-500 kPa), three primary categories of bubble behavior were observed optically: 1) no change in bubble diameter, 2) bubble shrinking (deflation), and 3) immediate bubble destruction (fragmentation). Matched acoustic data indicate that superharmonic signals having the broadest bandwidth and highest energy are associated with shell fragmentation. In the deflation case, a weaker superharmonic signal is produced with an amplitude approximately 25% of the signal in the shell fragmentation case. Similar regimes were observed in vivo, suggesting that bubble diameter, transmit frequency, peak negative pressure, and frame rate must be selected in light of the intended application, accounting for attenuation and local perfusion rate in the region of interest.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Lindsey, Brooks D. and Rojas, Juan D. and Martin, K. Heath and Shelton, Sarah E. and Dayton, Paul A.}, year={2014}, pages={1774–1777} }