High-frequency ultrasonic imaging with improved spatial resolution has gained increasing attention in the field of biomedical imaging. Sensitivity of transducers plays a pivotal role in determining ultrasonic image quality. Conventional ultrasonic transducers are mostly made from lead-based piezoelectric materials that may be harmful to the human body and the environment. In this study, a new (K,Na)NbO $_{3}$ -KTiNbO $_5$ -BaZrO $_{3}$ -Fe $_{2}$ O $_{3}$ -MgO (KNN-NTK-FM) lead-free piezoelectric ceramic was utilized in developing eco-friendly transducers for high-frequency biomedical ultrasonic imaging applications. A needle transducer with a small active aperture size of 0.45 × 0.55 mm $^2$ was designed and evaluated. The fabricated transducer exhibits great performance with a high center frequency (52.6 MHz), a good electromechanical coupling ( $k$ $_{eff}$ ~ 0.45), a large bandwidth (64.4% at -6 dB), and a very low two-way insertion loss (10.1 dB). Such high sensitivity is superior to those transducers based on other lead-free piezoelectric materials and can even be comparable to the lead-based ones. Imaging performance of the KNN-NTK-FM needle transducer was analyzed by imaging a wire phantom and an agar tissue-mimicking phantom. Imaging capabilities of the transducer were further demonstrated by ex vivo imaging studies on a porcine eyeball and a rabbit aorta. The results suggest that the KNN-NTK-FM piezoceramic has many attractive properties over other lead-free piezoelectric materials in developing eco-friendly highly sensitive transducers for high-frequency biomedical ultrasonic imaging applications.

Characterizing the viscoelastic properties of thin-layer tissues with micro-level thickness has long remained challenging. Recently, several micro-elastography techniques have been developed to improve the spatial resolution. However, most of these techniques have not considered the medium boundary conditions when evaluating the viscoelastic properties of thin-layer tissues such as arteries and corneas; this might lead to estimation bias or errors. This paper aims to integrate the Lamb wave model with our previously developed ultrasonic micro-elastography imaging system for obtaining accurate viscoelastic properties in thin-layer tissues. A 4.5-MHz ring transducer was used to generate an acoustic radiation force for inducing tissue displacements to produce guided wave, and the wave propagation was detected using a confocally aligned 40-MHz needle transducer. The phase velocity and attenuation were obtained from k-space by both the impulse and the harmonic methods. The measured phase velocity was fit using the Lamb wave model with the Kelvin-Voigt model. Phantom experiments were conducted using 7% and 12% gelatin and 1.5% agar phantoms with different thicknesses (2, 3, and 4 mm). Biological experiments were performed on porcine cornea and rabbit carotid artery ex vivo . Thin-layer phantoms with different thicknesses were confirmed to have the same elasticity; this was consistent with the estimates of bulk phantoms from mechanical tests and the shear wave rheological model. The trend of the measured attenuations was also confirmed with the viscosity results obtained using the Lamb wave model. Through the impulse and harmonic methods, the shear viscoelasticity values were estimated to be 8.2 kPa for 0.9 Pa·s and 9.6 kPa for 0.8 Pa·s in the cornea and 27.9 kPa for 0.1 Pa·s and 26.5 kPa for 0.1 Pa·s in the artery.

Objective: The ocular vascular system plays an important role in preserving the visual function. Alterations in either anatomy or hemodynamics of the eye may have adverse effects on vision. Thus, an imaging approach that can monitor alterations of ocular blood flow of the deep eye vasculature ranging from capillary-level vessels to large supporting vessels would be advantageous for detection of early stage retinal and optic nerve diseases. Methods: We propose a super-resolution ultrasound localization microscopy (ULM) technique that can assess both the microvessel and flow velocity of the deep eye with high resolution. Ultrafast plane wave imaging was acquired using an L22-14v linear array on a high frequency Verasonics Vantage system. A robust microbubble localization and tracking technique was applied to reconstruct ULM images. The experiment was first performed on pre-designed flow phantoms in vitro and then tested on a New Zealand white rabbit eye in vivo calibrated to various intraocular pressures (IOP) – 10 mmHg, 30 mmHg and 50 mmHg. Results: We demonstrated that retinal/choroidal vessels, central retinal artery, posterior ciliary artery, and vortex vein were all visible at high resolution. In addition, reduction of vascular density and flow velocity were observed with elevated IOPs. Conclusion: These results indicate that super-resolution ULM is able to image the deep ocular tissue while maintaining high resolution that is comparable with optical coherence tomography angiography. Significance: Capability to detect subtle changes of blood flow may be clinically important in detecting and monitoring eye diseases such as glaucoma.