Multimodal intravascular ultrasound and photoacoustic (IVUS/PA) imaging is a promising diagnostic tool for cardiovascular diseases like atherosclerosis. IVUS/PA catheters typically require two independent transducers due to different frequency requirements, potentially increasing the catheter size. To facilitate multimodal imaging within conventional catheter dimensions, we designed, fabricated, and characterized a dual-transducer acoustic stack where a low-frequency (LF) PA receiver sits as a matching layer for the high-frequency (HF) US transducer. While the HF transducer operates around 50 MHz, the LF receiver targets frequencies below 15 MHz to capture most of the PA energy from atherosclerotic plaque lipids. Simulation results reveal that this configuration could increase the sensitivity of the HF transducer by 3.54 dB while maintaining bandwidth. Phantom experiments with fabricated stacks showed improved performance for the US transducer, validating the enhanced sensitivity and bandwidth. Following improvements in stack fabrication, the proposed acoustic stack is a viable design that can significantly enhance diagnostic accuracy for atherosclerosis, providing high-resolution, multifrequency imaging within a compact catheter form factor.@en

Although high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited commercially available UCAs for high-frequency CEUS (hfCEUS) is largely unknown, while shell properties have been shown to be an important factor for their performance. The aim of our study was to produce UCAs in-house for hfCEUS. Twelve different UCA formulations A-L were made by either sonication or mechanical agitation. The gas core consisted of C₄F₁₀ and the main coating lipid was either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC; A-F formulation) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC; G-L formulation). Mechanical agitation resulted in UCAs with smaller microbubbles (number weighted mean diameter ∼1 μm) than sonication (number weighted mean diameter ∼2 μm} ). UCA formulations with similar size distributions but different main lipid components showed that the DPPC-based UCA formulations had higher nonlinear responses at both the fundamental and subharmonic frequencies in vitro for hfCEUS using the Vevo2100 high-frequency preclinical scanner (FUJIFILM VisualSonics, Inc.). In addition, UCA formulations F (DSPC-based) and L (DPPC-based) that were made by mechanical agitation performed similar in vitro to the commercially available Target-Ready MicroMarker (FUJIFILM VisualSonics, Inc.). UCA formulation F also performed similar to Target-Ready MicroMarker in vivo in pigs with similar mean contrast intensity within the kidney ( n = 7 ), but formulation L did not. This is likely due to the lower stability of formulation L in vivo. Our study shows that DSPC-based microbubbles produced by mechanical agitation resulted in small microbubbles with high nonlinear responses suitable for hfCEUS imaging.

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