Extending the Transmit and Receive Bandwidths of Dual-Frequency Transducers Toward Clinical Acoustic Angiography: In Vitro and In Vivo Studies

The acoustic angiography leverages the superharmonic response of microbubbles against linear tissue to generate 3-D maps of microvasculature. This contrast-enhanced ultrasound imaging approach uses dual-frequency (DF) transducers that transmit at frequencies less than 5 MHz and receive at frequencies three times or greater than the fundamental frequency to selectively detect microbubble signals. Previous iterations of the hardware were designed mainly to image preclinical models. In pilot clinical imaging studies, these transducers suffered from poor microbubble sensitivity and shallow imaging depths. Here, we investigate multiple DF transducers operating at varying transmit frequencies less than 2 MHz and center receive frequencies ranging from 7 to 18 MHz designed for deeper imaging and greater bubble sensitivity than earlier generation devices. We assess the superharmonic imaging (SpHI) performance of these transducers in vitro and in vivo by characterizing contrast sensitivity and resolution. We demonstrate improvements in sensitivity at lower transmit (<1 MHz) and receive (<10 MHz) frequencies, measuring contrast signal enhancement up to 31.8 dB. At these lower frequencies, we also achieve imaging depths up to 50–55 mm—the deepest application of acoustic angiography to date. These advances in imaging sensitivity and depth address the primary barriers to the clinical translation of acoustic angiography.