Research Advances in Ultrasound Imaging for Tumor in Situ

Ultrasound (US) is a type of mechanical wave that is capable of transmitting energy through biological tissues. By utilization of various frequencies and intensities, it can elicit specific biological effects. US imaging (USI) technology has been continuously developed with the advantages of safety and the absence of radiation. The advancement of nanotechnology has led to the utilization of various nanomaterials composed of both organic and inorganic compounds as ultrasound contrast agents (UCAs). These UCAs enhance USI, enabling real-time monitoring, diagnosis, and treatment of diseases, thereby facilitating the widespread adoption of UCAs in precision medicine. In this review, we introduce various UCAs based on nanomaterials for USI. Their principles can be roughly divided into the following categories: carrying and transporting gases, endogenous gas production, and the structural characteristics of the nanomaterial itself. Furthermore, the synergistic benefits of US in conjunction with various imaging modalities and their combined application in disease monitoring and diagnosis are introduced. In addition, the challenges and prospects for the development of UCAs are also discussed.

Recent Advancements in Ultrasound Contrast Agents Based on Nanomaterials for Imaging

Ultrasound contrast agents (UCAs) such as SonoVue or Optison have been used widely in clinic
for contrast-enhanced vascular imaging. However, microbubbles UCAs display limitations in
tumor-targeted imaging due to the large sizes, nanoscaled UCAs has consequently attracted increasing
attentions. In this work, we synthesized nanobubbles (NBs) by ultrasonic cavitation method, then a
fluorescent marker of Alexa Fluor 680 was conjugated to the shell in order to observe the localization
of NBs in tumor tissue. Measurement of fundamental characteristics showed that the NBs had
homogeneous distribution of mean diameter of 267.9 ± 19.2 nm and polydispersity index of 0.410 ±
0.056. To assess in vivo tumor-selectivity of NBs, we established the rabbits VX2 hepatocellular
carcinoma model though surgical implantation method. After the rabbits were intravenous administered
of NBs, contrast-enhanced sonograms was observed in the surrounding of VX2 tumor, which showed
there are rich capillaries in the tumor periphery. We additionally investigated the toxic of the NBs by
hematoxylin-eosin staining. The results indicated that the NBs is a biocompatible non-toxic lipid
system. Furthermore, the VX2 tumors and major organs were analyzed using ex vivo fluorescence
imaging to confirm the targeted selectivity of NBs, and the results verified that the NBs were capable
of targeting VX2 tumor. Confocal laser scanning microscopy examination showed that the NBs can
traverse the VX2 tumor capillaries and target to the hepatocellular carcinoma tumor cells. All these
results suggested that the newly prepared NBs have a potential application in molecular imaging and
tumor-targeting therapy.

Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model

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Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model