Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery

Ultrasound is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents. There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular contrast agents enable functional analyses, e.g. to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by ultrasound pulses to locally release the entrapped agent. Recent studies show that ultrasound contrast agents are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of ultrasound contrast agents and introduces the current clinical applications of contrast-enhanced ultrasound. Additionally, an overview of the recent developments in ultrasound probe design for functional and molecular diagnosis as well as for drug delivery is given

MR and PET-CT monitoring of tissue-engineered vascular grafts in the ovine carotid artery

The modification of biomaterials to comply with clinically employed monitoring techniques is a promising strategy to support clinical translation in regenerative medicine. Here, multimodal imaging of tissue-engineered vascular grafts (TEVG) was enabled by functionalizing the textile scaffold with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The resulting MR-imageable grafts (iTEVG) were monitored non-invasively throughout their whole life-cycle, from initial quality control to longitudinal functional evaluation in an ovine model for up to 8 weeks. Crucial features such as the complete embedding of the textile mesh in the developing tissue and the grafts’ structural stability were assessed in vitro using 1T-, 3T- and 7T-MRI scanners. In vivo, the grafts were imaged by 3T-MRI and PET-CT. Contrary to unlabeled constructs, iTEVG could be delineated from native arteries and precisely localized by MRI. USPIO labeling neither induced calcifications, nor negatively affected their remodeling with respect to tissue-specific extracellular matrix composition and endothelialization. Functionality was confirmed by MR-angiography. 18F-FDG uptake (assessed via PET-CT) indicated only transient post-surgical inflammation. In conclusion, USPIO-labeling enables accurate localization of TEVG and opens up opportunities for multimodal imaging approaches to assess transplant acceptance and function. Thereby, it can support clinical decision-making on the need for further pharmacological or surgical interventions

Corrigendum to “MR and PET-CT monitoring of tissue-engineered vascular grafts in the ovine carotid artery” [Biomaterials 216 (2019) 119228] (Biomaterials (2019) 216, (S0142961219303278), (10.1016/j.biomaterials.2019.119228))

The authors regret that a statement on author contributions was not correctly formulated. With this corrigendum we provide the corrected version. Author contributions FW and SK prepared the tissue-engineered vascular grafts and were responsible of the study's coordination. FW, SK, AR and PM performed the tissue analysis and interpretation. SJ, TL, FM and FK were responsible for the study design. VF, MM and NG-W performed the in vitro and in vivo MR monitoring of grafts and the MRI data analysis together with TL, FK, PM and FW. OW and AM performed the PET- CT monitoring of grafts and the data analysis together with FM, PM and FW. HS and KC were responsible for the surgical implantation of the grafts. FW drafted the original manuscript; PM, TL and FK critically revised it. All authors discussed the results and approved the final version of the manuscript. The authors would like to apologise for any inconvenience caused