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.

Matching the acoustic impedance of high-frequency (≥100 MHz) ultrasound transducers to an aqueous loading medium remains a challenge for fabricating high-frequency transducers. The traditional matching layer design has been problematic to establish high matching performance given requirements on both specific acoustic impedance and precise thickness. Based on both mass-spring scheme and microwave matching network analysis, we interfaced metal-polymer layers for the matching effects. Both methods hold promises for guiding the metal-polymer matching layer design. A 100 MHz LiNbO₃ transducer was fabricated to validate the performance of the both matching layer designs. In the pulse-echo experiment, the transducer echo amplitude increased by 84.4% and its −6dB bandwidth increased from 30.2% to 58.3% comparing to the non-matched condition, demonstrating that the matching layer design method is effective for developing high-frequency ultrasonic transducers.

Imaging of coronary vasa vasorum may lead to assessment of the vulnerable plaque development in diagnosis of atherosclerosis diseases. Dual frequency transducers capable of detection of microbubble super-harmonics have shown promise as a new contrast-enhanced intravascular ultrasound (CE-IVUS) platform with the capability of vasa vasorum imaging. Contrast-to-tissue ratio (CTR) in CE-IVUS imaging can be closely associated with low frequency transmitter performance. In this paper, transducer designs encompassing different transducer layouts, transmitting frequencies, and transducer materials are compared for optimization of imaging performance. In the layout selection, the stacked configuration showed superior super-harmonic imaging compared with the interleaved configuration. In the transmitter frequency selection, a decrease in frequency from 6.5 MHz to 5 MHz resulted in an increase of CTR from 15 dB to 22 dB when receiving frequency was kept constant at 30 MHz. In the material selection, the dual frequency transducer with the lead magnesium niobate-lead titanate (PMN-PT) 1–3 composite transmitter yielded higher axial resolution compared to single crystal transmitters (70 μ m compared to 150 μ m pulse length). These comparisons provide guidelines for the design of intravascular acoustic angiography transducers.

The ability to image tissue morphogenesis in real-time and in 3-dimensions (3-D) remains an optical challenge. The advent of light-sheet fluorescence microscopy (LSFM) has advanced developmental biology and tissue regeneration research. In this review, we introduce a LSFM system in which the illumination lens reshapes a thin light-sheet to rapidly scan across a sample of interest while the detection lens orthogonally collects the imaging data. This multiscale strategy provides deep-tissue penetration, high-spatiotemporal resolution, and minimal photobleaching and phototoxicity, allowing in vivo visualization of a variety of tissues and processes, ranging from developing hearts in live zebrafish embryos to ex vivo interrogation of the microarchitecture of optically cleared neonatal hearts. Here, we highlight multiple applications of LSFM and discuss several studies that have allowed better characterization of developmental and pathological processes in multiple models and tissues. These findings demonstrate the capacity of multiscale light-sheet imaging to uncover cardiovascular developmental and regenerative phenomena.

Acoustic filters (AFs) are key components to control wave propagation in multi-frequency systems. We present a design which selectively achieves acoustic filtering with a stop band and passive amplification at the high- and low-frequencies, respectively. Measurement results from the prototypes closely match the design predictions. The AF suppresses the high frequency aliasing echo by 14.5 dB and amplifies the low frequency transmission by 8.0 dB, increasing an axial resolution from 416 to 86 μm in imaging. The AF design approach is proved to be effective in multi-frequency systems.

High-intensity focused ultrasound (HIFU) treatment efficiency is critical in maximizing the hyperthermia and reducing the surgery time. In this paper, a single-aperture, 1.5 MHz/3 MHz dual-frequency HIFU transducer was designed, fabricated, and characterized for tissue ablation enhancement. Double PZT-2 layers were configured in serial and dual-frequency ultrasound waves can be concurrently generated by exciting one of the PZT-2 layers. Impulse responses from the prototype showed that the wave amplitudes at 1.5 and 3 MHz were about the same, and both are more than 12 dB larger than those of higher orders of harmonics. Tissue ablation tests demonstrated that higher temperature rise can be achieved with dual-frequency ultrasound than with single-frequency ablation at the same acoustic power.