Abstract

The high efficiency with which gas microbubbles can scatter ultrasound compared with the surrounding blood pool or tissues has led to their widespread employment as contrast agents in ultrasound imaging. In recent years, their applications have been extended to include super-resolution imaging and the stimulation of localized bio-effects for therapy. The growing exploitation of contrast agents in ultrasound and in particular these recent developments have amplified the need to characterize and fully understand microbubble behavior. The aim in doing so is to more fully exploit their utility for both diagnostic imaging and potential future therapeutic applications. This paper presents the key characteristics of microbubbles that determine their efficacy in diagnostic and therapeutic applications and the corresponding techniques for their measurement. In each case, we have presented information regarding the methods available and their respective strengths and limitations, with the aim of presenting information relevant to the selection of appropriate characterization methods. First, we examine methods for determining the physical properties of microbubble suspensions and then techniques for acoustic characterization of both suspensions and single microbubbles. The next section covers characterization of microbubbles as therapeutic agents, including as drug carriers for which detailed understanding of their surface characteristics and drug loading capacity is required. Finally, we discuss the attempts that have been made to allow comparison across the methods employed by various groups to characterize and describe their microbubble suspensions and promote wider discussion and comparison of microbubble behavior.

Highlights

  • G AS microbubbles are in widespread use as contrast agents in ultrasound imaging as a result of their exceptional echogenicity [1], [2]

  • This paper presents the means by which different research groups have sought to characterize and compare microbubbles for diagnostic and therapeutic applications

  • Where results are to be used to gain insight to behavior in vivo, careful control of temperature, gas saturation, and preparation and handling methods used are essential to give reliable results

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Summary

INTRODUCTION

G AS microbubbles are in widespread use as contrast agents in ultrasound imaging as a result of their exceptional echogenicity [1], [2]. Their use in super-resolution imaging techniques, which offer unprecedented detail in ultrasound imaging, is currently being explored [7], [8]. We discuss the methods for comparing data sets from across the literature

Introduction
Optical Microscopy for Microbubble Suspension Characterization
Optical Scattering Methods
Electro-Impedance Volumetric Zone Sensing
Important Points to Note
Bulk Suspensions
Methods of Standardizing Results for Comparison Across Research Groups
Single Microbubble Techniques
OPTICAL CHARACTERIZATION OF ULTRASOUND CONTRAST AGENTS
Ultrahigh Speed Imaging Facilities
Optical Characterization Techniques
Modeling and Mechanical Approaches
Fluorescence Microscopy
Electron Microscopy
Characterization of Microbubble Chemistry
Drug Loading Quantification
CONCLUSION
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