Organic nanoparticle-doped microdroplets as dual-modality contrast agents for ultrasound microvascular flow and photoacoustic imaging

Abstract

Tumor blood vessels are chaotic and abundantly distributed, owing to their heterogeneity. Therefore, imaging techniques which reveal abnormalities of tumor vasculature play significant roles in both mechanistic and clinical diagnostic tumor studies. Photoacoustic (PA) imaging uses the intrinsic characteristics of hemoglobin, to acquire tumor hemodynamic information, while ultrasound (US) imaging provides information about tumoral vessel structures and blood flow. To improve the imaging contrast performance, hydrogel-based microdroplets were designed for both US blood flow and PA imaging in this study. The microdroplets served as carriers for PA contrast agent solution in the innermost part while oil and hydrogel formed the inner and outer layers of the droplets. In vitro experiments firstly demonstrated the dual modality contrast effects of the microdroplets on US flow determination and PA imaging. In vivo experiments were then carried out in both healthy nude mice and nude mice with subcutaneous tumor to validate the contrast effects and to monitor the duration of contrast effects in animals. Using the dual-modality microdroplets, we were able to obtain distinct edges of tumor and blood flow mapping of the tumor microvascular with improved sensitivity up to 11.09 dB for PA and 6.69 dB for US flow. Besides, the in vivo evaluation with microdroplets showed US flow enhancement for more than 60 min. Therefore, the microdroplets are able to provide the contrast effects for both US flow and PA in a relative long duration and have potential to be applied in the tumor related diagnoses and studies.

Synthesis, rheological characterization, and proposed application of pre‐polyglycerol sebacate as ultrasound contrast agent based on theoretical estimation

“…Xu et al synthesized nanoparticles doped alginate hydrogel‐based microdroplets for dual imaging via ultrasound and photoacoustic imaging. The microdroplets showed higher stability however, echogenicity was three times lower than the standard Sonovue contrast agent 10 . Since the study did not focus on viscoelastic response in the acoustic field, the reason for low enhancement can not be clearly explained however high viscosity of alginate hydrogels could be one of the reasons 10,11 .…”

“…The microdroplets showed higher stability however, echogenicity was three times lower than the standard Sonovue contrast agent 10 . Since the study did not focus on viscoelastic response in the acoustic field, the reason for low enhancement can not be clearly explained however high viscosity of alginate hydrogels could be one of the reasons 10,11 . Elastomers are a class of polymers with flexible nature.…”

“…The echogeneicity of polymeric microbubbles can be increased by using polymers with low elastic modulus and viscosity, that is, elastomers and hydrogels. Recent studies are focused on developing microbubbles from hydrogels 8–10 . Xu et al synthesized nanoparticles doped alginate hydrogel‐based microdroplets for dual imaging via ultrasound and photoacoustic imaging.…”

MXenes-polymer nanocomposites for biomedical applications: fundamentals and future perspectives

“… Xu et al (2020) developed MXene-polymer nanocomposites as dual-modal contrast agents for both photoacoustic imaging (PAI) and MRI. The nanocomposites exhibited excellent imaging performance with high signal intensity and superior contrast enhancement in tumor imaging ( Xu et al, 2020 ). Kong and Chen in 2022 reported the synthesis of MXene-polymer nanocomposites as theranostic agents for combined photothermal therapy (PTT) and photodynamic therapy (PDT) of cancer ( Kong and Chen, 2022 ).…”

Optical Microscopy Systems for the Detection of Unlabeled Nanoparticles

“… 83 For tumor vessel imaging, Xu et al used the intrinsic properties of hemoglobin for PA imaging and ultrasound imaging to gain information about blood flow. 128 A dual contrast agent based on alginate-hydrogel microdroplets encapsulating conjugated polymeric NPs enabled a detailed blood flow mapping in tumor microvessels of mice with clear tumor edges. Miao et al developed a multimodal infrared fluorescent and photoacoustic contrast agent based on a fluorescent NP copolymer with a high photothermal conversion efficiency for photothermal therapy.…”