Imaging with ultrasound contrast agents: current status and future

Abstract

Microbubble ultrasound contrast agents (UCAs) were recently approved by the Food and Drug administration for non-cardiac imaging. The physical principles of UCAs, methods of administration, dosage, adverse effects, and imaging techniques both current and future are described. UCAs consist of microbubbles in suspension which strongly interact with the ultrasound beam and are readily detectable by ultrasound imaging systems. They are confined to the blood pool when administered intravenously, unlike iodinated and gadolinium contrast agents. UCAs have a proven safety record based on over two decades of use, during which they have been used in echocardiography in the U.S. and for non-cardiac imaging in the rest of the world. Adverse effects are less common with UCAs than CT/MR contrast agents. Compared to CT and MR, contrast-enhanced ultrasound has the advantages of real-time imaging, portability, and reduced susceptibility to metal and motion artifact. UCAs are not nephrotoxic and can be used in renal failure. High acoustic amplitudes can cause microbubbles to fragment in a manner that can result in short-term increases in capillary permeability or capillary rupture. These bioeffects can be beneficial and have been used to enhance drug delivery under appropriate conditions. Imaging with a mechanical index of < 0.4 preserves the microbubbles and is not typically associated with substantial bioeffects. Molecularly targeted ultrasound contrast agents are created by conjugating the microbubble shell with a peptide, antibody, or other ligand designed to target an endothelial biomarker associated with tumor angiogenesis or inflammation. These microbubbles then accumulate in the microvasculature at target sites where they can be imaged. Ultrasound contrast agents are a valuable addition to the diagnostic imaging toolkit. They will facilitate cross-sectional abdominal imaging in situations where contrast-enhanced CT and MR are contraindicated or impractical.

<p>Safety Profile of Musculoskeletal Contrast-Enhanced Ultrasound with Sulfur Hexafluoride Contrast Agent</p>

“…In musculoskeletal applications, CEUS represents a complementary investigative approach, which offers certain advantages in comparison to conventionally used diagnostic instruments such as DCE-MRI or DCE-CT. 34 Contrary to MRI, CT and X-ray examinations, the costeffective CEUS can be safely used in patients with renal impairment, without ionizing radiation or deposition of contrast agents in human body and fear of claustrophobia. 15,[35][36][37] Considering, among other things, the resolution and frame rate of CEUS, whose detail accuracy is superior to conventional MRI, CEUS may soon be able to support other time-consuming and cost-intensive medical investigations for various indications. 36…”

“…Considering the contraindications of sulfur hexafluoride contrast agents and the current state of scientific knowledge, patients were not exposed to any additional health damage or additional risk. 15 Once a patient showed an adverse event to the contrast agent, he was excluded from the study.…”

“…Moreover, CEUS is easily accessible, quick to use, well tolerated by patients and allows a real-time diagnostic workup. 15 Since 2012, musculoskeletal CEUS examinations were applied to assess microperfusion of tendon, muscle, 16,17 as well as osseous perfusion of healing bone, 18,19 infected nonunions and its surrounding tissue 20,21 for various clinical issues. Among multiple interactions and relationships, a strong correlation could be demonstrated between CEUSbased muscle perfusion of the deltoid or supraspinatus muscle with shoulder function before and after surgery, potentially allowing an outcome prediction for eg tendon integration after rotator cuff repair by preoperative CEUS.…”

Toolbox for In Vivo Imaging of Host–Parasite Interactions at Multiple Scales

“…Ultrasound uses high-frequency sound waves, which are reflected off of body structures, rendering an image. Key advances in ultrasound over the past decade include elastography [110], ultrasound contrast agent imaging using micro-bubbles (reviewed by [111]), super resolution imaging, 2D array transducer, and ultra-fast ultrasound imaging [112]. While these advances have been widely explored in other fields of research, they remain to be used in in vivo parasitology, and have enormous potential.…”

Porous upconversion nanostructures as bimodal biomedical imaging contrast agents

“…Correspondingly, various exogenous materials as contrast agents are adopted for specific techniques to enhance signal-to-noise ratio [6]. For instance, nano-bubbles can enhance the ultrasound scanning resolution [4,[7][8][9], Iodine-based and barium-sulfate based material with strong X-ray absorption are used for CT and PET [6,10] , and magnetic materials such as iron oxide or gadolinium compounds are best for MRI to gain paramagnetic signals [11,12]. Fluorescent dyes, such as firefly luciferase (FLuc), is benefited by very high sensitivity in bioluminescence imaging and a broad dynamic range relative to other imaging techniques.…”