Duplex dual-frequency CMUT array for acoustic angiography - PROJECT SUMMARY: In this project we propose to develop and validate new ultrasound hardware technologies for high-contrast, high- resolution microvascular imaging to detect abnormalities in vascular morphology which can be biomarkers for a variety of disease ranging from cancer to dementia. Computed tomography angiography (CTA), photoacoustic microvascular imaging (PMI), and magnetic resonance angiography (MRA) have been used to image the micro- vasculature. However, it is highly desired to image the microvasculature using ultrasound alone. Ultrasonic Dop- pler imaging, acoustic angiography (AA), and ultrasound localization microscopy (ULM), which utilizes contrast enhanced ultrasound (CEUS) and ultrafast ultrasound imaging, have been demonstrated to be capable of provid- ing high contrast to tissue as well as high spatial resolution when imaging the microvasculature. Implementation of AA has long been challenged by the availability of transducer arrays that have a sufficiently wide bandwidth to excite microbubbles at low frequencies (LF) and receive the bubble generated harmonics at high frequencies (HF). In this project, we propose a novel capacitive micromachined ultrasonic transducer (CMUT) array structure, which is composed of a stack of a LF transmit (TX) elements and HF receive (RX) elements, fabricated one on top of the other, by using lithography-based microfabrication techniques. This approach allows independent op- timization of LF transmitters and HF receivers in the same physical area, hence resulting in entirely overlapping TX and RX apertures. The ability to independently design the TX and RX elements enables a large separation between the TX and RX frequency bands with no spectral overlap. Our long-term goal is the clinical translation of AA to enable imaging of morphology and function of microvasculature for improved diagnostics and therapy monitoring for pathologies including stroke, cancer, and dementia. The specific objective of this developmental project is to design and implement a custom imaging probe that includes the described duplex, dual frequency 1D CMUT arrays and supporting custom frontend electronics, all validated in small animal models. As the pro- posed project requires a high degree of innovation in array design and fabrication with potential results that can transform acoustic angiography to clinical space, the R21 mechanism is ideal to establish basic feasibility. Spe- cific aims of the project are as follows: 1) Design and implement duplex dual frequency 1D CMUT arrays with 32 TX elements operating in the 1-3 MHz band, and 256 RX elements operating in the 10-30 MHz band. 2) Design and implement custom frontend electronics combining linear TX drivers and low-noise wideband RX preamplifi- ers. 3) Validate and characterize the device in-vivo imaging performance in small animal models. The described CMUT structure with two arrays, i.e., LF and HF, microfabricated as a stack has never been proposed. Further- more, we innovate in the frontend electronics design to generate LF transmit pulses with minimal harmonic content to maximize the contrast-to-tissue ratio in the images. Our team has been collaborating on this significant application for over 5 years and therefore is in a great position to successfully execute the proposed project.
