# Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy
## 1 Introduction  
Ultrasound (US) is widely used in clinics and has become a traditional diagnostic strategy for various diseases due to outstanding profiles such as low cost, ionization-free radiation, real-time availability, portable operation, etc. [1]. US imaging has been applied in vast fields from abdomen or superficial lesions to heart and intracavitary examinations. In order to enhance the image contrast and resolution, ultrasound contrast agents (UCAs) are always used in clinical diagnosis. [PERSON] and [PERSON] first reported UCAs in echocardiography in 1968 [2]. The saline injection was administered in heart which dramatically improved the quality of ultrasonography due to the bubbles in the contrast medium. In this sense, contrast-enhanced ultrasonography (CEUS) has been investigated in the last decades and has become a routine method to diagnose diseases with comparable contrast enhancement with computed tomography (CT) or magnetic resonance imaging (MRI) [3]. Thus, US exhibits great potential as a powerful diagnostic tool to detect pathological behavior with prominent precision and efficiency. Moreover, UCAs have been applied not only for diagnosis but also for therapy such as thrombolysis and drug delivery. UCAs such as microbubbles have proved effective in curing intravascular thrombus [4]. [PERSON] et al. disclosed that high-intensity focused ultrasound associated with UCAs could be used in the liver treatment [5]. The microbubbles could be destroyed by ultrasound, and the permeability of cell membranes could be increased, enabling them to perform drug/gene delivery [6; 7]. Therefore, UCAs present a great opportunity not only as a powerful diagnostic tool but also as a multifunctional platform to serve therapeutic purposes in clinics. Further perspectives by using microbubbles (MBs) as UCAs and drug/gene delivery carriers will imply emerging developmentsand even broader applications in assisting disease treatments with this versatile platform. At present, several kinds of commercial UCAs have been approved in clinical applications (Table 1). Levovist and Albunex can be used in cardiovascular imaging; however, because of their disadvantages of bad enhancement effect and short duration, Levovist and Albunex gradually exited the contrast media market around 2000. SonoVue is mainly used to characterize liver lesions. The use of SonoVue to assess the early response to anti-angiogenic drugs in cancer chemotherapy has been studied. With promising results, wider studies are ongoing. Optison was much more effective at killing cells than other agents, and may be the best US microbubble contrast agent for gene therapy [8]. The UCAs whose gas core contain C3F8 are considered the best material for microvascular imaging. Over the past few years, ultrasound molecular imaging (UMI) and ultrasound molecular therapy (UMT) have made leaps toward everlasting developments in both preclinical and clinical investigations to detect the disease processes at the molecular or cellular level in a visualizable manner. With the introduction of novel specific biomarker-targeted UCAs, early-stage detection and therapy will be achieved. At present, these studies mainly focus on the fields of tumor detection, inflammation, cardiovascular diseases, blood-brain barrier (BBB) disruption, brain metastasis, thrombolysis and related interdisciplinary sections (Figure 1). \begin{table}
\begin{tabular}{c c c c c c c} \hline
**UCAs** & **Albunex** & **Optison** & **Levovist** & **SonoVue** & **Definity** & **Sonazol** \\ \hline \multirow{2}{*}{**Manufacturer**} & Molecular Biosystems & \multirow{2}{*}{Amersham} & \multirow{2}{*}{Schering AG.}