In vivo ocular microvasculature imaging in rabbits with 3D ultrasound localization microscopy.

Morphological and hemodynamic changes in the ocular vasculature are important signs of various ocular diseases. The evaluation of the ocular microvasculature with high resolution is valuable in comprehensive diagnoses. However, it is difficult for current optical imaging techniques to visualize the posterior segment and retrobulbar microvasculature due to the limited penetration depth of light, particularly when the refractive medium is opaque. Thus, we have developed a 3D ultrasound localization microscopy (ULM) imaging method to visualize the ocular microvasculature in rabbits with micron-scale resolution. We used a 32 × 32 matrix array transducer (center frequency: 8 MHz) with a compounding plane wave sequence and microbubbles. Block-wise singular value decomposition spatiotemporal clutter filtering and block-matching 3D denoising were implemented to extract the flowing microbubble signals at different imaging depths with high signal-to-noise ratios. The center points of microbubbles were localized and tracked in 3D space to achieve the micro-angiography. The in vivo results demonstrate the ability of 3D ULM to visualize the microvasculature of the eye in rabbits, where vessels down to 54 µm were successfully revealed. Moreover, the microvascular maps indicated the morphological abnormalities in the eye with retinal detachment. This efficient modality shows potential for use in the diagnosis of ocular diseases.

Sonodynamic Therapy With Concentric Ultrasound Imaging Array for Precision Theranostics for Atherosclerotic Plaque.

Atherosclerotic cardiovascular disease is a major cause of human disability and mortality. Our previous study demonstrated the safety and efficacy of sonodynamic therapy (SDT) on atherosclerotic plaques. However, traditional single-element therapeutic transducer has single acoustic field, and positioning therapeutic and imaging transducers in the same position is difficult during ultrasound imaging-guided SDT. Continuously changing the position of transducers to intervene lesions in different positions is required, increasing the difficulty of treatment. Thus, an SDT device with precise theranostics is required. Therefore, we designed and fabricated a "concentric ultrasound transducer for theranostics" (CUST-T), comprising a central 8-MHz linear array transducer for ultrasound imaging, and a peripheral 1-MHz hollow two-dimensional (2-D) planar array transducer for generating phased-array focused ultrasound (PAFUS). The CUST-T exhibited high imaging resolution at a distance of up to 20 mm from the transducer and could generate a personalized complex PAFUS acoustic field to match various lesions. In vitro biomedical results showed that PAFUS-SDT induced RAW264.7-derived foam cell apoptosis leading to a targeting field apoptotic rate 4.36-6.24 times that of the nontargeting field and the significant apoptotic region was consistent with the PAFUS acoustic field. In vivo, PAFUS-SDT guided by ultrasound imaging significantly increased the lumen area ( ) and collagen level ( ), whereas the wall thickness ( ) and lipid content ( ) of rabbit femoral artery were reduced. In conclusion, CUST-T provided image guidance sufficient for accurate SDT for atherosclerotic plaques in peripheral arteries and could be applied in clinical practice.

Endoscopic Ultrasound Localization Microscopy for the Evaluation of the Microvasculature of Gastrointestinal Tract Tumors in Rabbits.

OBJECTIVE: The morphological and hemodynamic characterization of the microvascular network around the gastrointestinal (GI) tract can be of significant clinical value for the early diagnosis and treatment of GI tract cancer. Ultrasound localization microscopy (ULM) imaging has been demonstrated to be capable of resolving the microvascular network. However, the endoscopic application of ULM imaging techniques is still unknown. In this study, an endoscopic ultrasound localization microscopy (e-ULM) imaging technique was developed to evaluate the changes of microvasculature during GI tract tumor growth. METHODS: A customized circular array transducer (center frequency: 6.8 MHz) and the coherent diverging wave compounding method were used to generate B-mode images. Spatiotemporal singular value decomposition processing was used to eliminate the background signals before signal localizations. The centroids of spatially isolated signals were localized and summed to generate the final super-resolution image. RESULTS: The final microvasculature map of a rabbit GI tract tumor reveals that e-ULM can be used to surpass the diffraction limit in traditional endoscopic ultrasound (EUS) imaging. Furthermore, it is observed that data from different stages of tumor growth exhibit significant differences in microvascular pattern and density. CONCLUSION: Our study demonstrated the implementation and application of an in vivo e-ULM imaging technique for the evaluation of the microvasculature of GI tumors. SIGNIFICANCE: The efficient e-ULM imaging technique shows potential for use in the detection of GI tract tumor microcirculation changes and subsequent diagnosis of GI tract cancer.

In Vivo Ultrasound Localization Microscopy Imaging of the Kidney's Microvasculature With Block-Matching 3-D Denoising.

Structural abnormalities and functional changes of renal microvascular networks play a significant pathophysiologic role in the occurrence of kidney diseases. Super-resolution ultrasound imaging has been successfully utilized to visualize the microvascular network and provide valuable diagnostic information. To prevent the burst of microbubbles, a lower mechanical index (MI) is generally used in ultrasound localization microscopy (ULM) imaging. However, high noise levels lead to incorrect signal localizations in relatively low-MI settings and deep tissue. In this study, we implemented a block-matching 3-D (BM3D) image-denoising method, after the application of singular value decomposition filtering, to further suppress the noise at various depths. The in vitro flow-phantom results show that the BM3D method helps the significant reduction of the error localizations, thus improving the localization accuracy. In vivo rhesus macaque experiments help conclude that the BM3D method improves the resolution more than other image-based denoising techniques, such as the nonlocal means method. The obtained clutter-filtered images with fewer incorrect localizations can enable robust ULM imaging, thus helping in establishing an effective diagnostic tool.