Ultrasound contrast agents (USCA)

Ultrasound contrast agents (USCA)

Ultrasound contrast agents (USCA) are one of the emerging developments in molecular imaging procedures used by the clinicians to treat various diseases. USCA for intravenous injections are gas-filled microbubbles having a diameter of less than that of a red blood corpuscle.

 According to Jakobsen (2001), USCA improvement depends on different factors, which includes pharmacodynamic and pharmacokinetic properties of the products that determine the kinds of effects on the various ultrasound-imaging techniques (1329). These agents requires  a combination of the medical and technical knowledge  by the examiner, better equipment and a presence of a disease that can be diagnosed using USCA as well as  a cooperative  patient. According to Correas, Bridal, Lesavre, Mejean, Claudon, Helenon (2001), USCA is one of the agents that can improve detection, characterization and follow up of diseases or parenchyma organs and various vascular beds in the entire body of a person (1316). Correas et al (2001) states that contrast-imaging concept was introduced 30 years ago (1316).  The development of USCA was slow initially because of the technical limitations. However, it has become dynamic in the previous decades. There are ideals associated with USCA which includes   properties of being injectable intravenously, non-toxic, and the capability to cross-pulmonary capillary bed after a peripheral injection. Furthermore, it should be stable to achieve enhancement during the period of examination (Correas, Bridal, Lesavre, Mejean, Claudon, Helenon 2001, 1316).  Furthermore, this agent has been established to be cost effective as it also provides gray-scale and Doppler enhancement. Doppler examinations are usually enhanced using USCA especially when the doctor is studying small vessels and deeper vessels that have slow or low flow or vessels that have non-optimal insonaiton angle.  These USCA agents are effective in enhancing of flow in blood in abnormal vessels, including stenotic vessels and tumor vascularization.  They also provide better delineation especially in the ischemic zones/areas.

According to Correas, Bridal, Lesavre, Mejean, Claudon,  and Helenon (2001), USCA have proven to be more advantageous compared to other  types of imaging procedures such as computed tomography, magnetic resonance,  and optical imaging  in the  field of imaging molecular(1316). This is because USCA have high spatial resolution of ultrasound contrast agents in the micrometer range and single, gas filled micro-particles. Furthermore, their high sensitivity can be imaged and even quantified (Duvshani-Eshet and Machluf 2007, 306). Contrast media are currently used in various imaging modalities and are commercially available from various dealers. These agents have a number of benefits to the users. One of the advantages is that they do not exhibit allergic reactions or any cases of toxicity. They further increase dropper signal intensity in vessels that are deeply located, have small caliber, have a reduced or slow blood flow and have anatomic limitations. According to Dong, Ke, Yun-Hua , Kai-Bin, and Zheng (2010),  ultrasound  contrasts agents  have been used  to improve on the specificity and sensitivity  of  disease detection because they have capability to reflect the signal from the blood flow (288). They are further used in enhancement of backscattered signal and improvement of resolution. In general, these agents are comprised of stabilized gas bubbles. One of the principles that cut across all ultrasound contrast agents is their impedance mismatch between the agent, which is gas, and the surrounding medium that consists of blood and soft tissues. Ultrasound molecular imaging has experienced rapid development because of the advanced research.  Stability of nanoscale ultrasound makes it one of the effective agents to enhance ultrasound imaging.

There are different categories of USCA used in different ways. One of them is SHU 563A that is applicable for specific tissues such as retuculoendothelial system, Optison used in cases relating with the blood flow measurement and Galactose micro particles, renografin 76 and Albuminen capsulated bubbles among many others applicable in cardiac cases. There are various USCA image sequences used which include resonant frequencies in the range of medical interest, harmonic and pulse imaging sequences, harmonic imaging that includes color, spectral, B-mode and power imaging. Others are use of acoustic pressures that are between 0.1-0 Mpa  u-bubbles  that resonates producing  harmonics (Correas, Bridal, Lesavre, Mejean, Claudon, and Helenon 2001, 1316). There is suppression of tissues in B-mode harmonic echoes while in spectral harmonic clutter from vessels is usually rejected without signal filtering. On the other hand, there is reduction of color harmonic flash artifacts and delectation of smaller vessels. According to Wood et al. (2012), gas filled micro bubble contrast agents are used in enhancing ultrasound imaging (1).  At the tissue gas interface, strong echo signals are introduces as the micro bubble collapses. It can be applied in the assessment of virtual histology as well as ventricular function. Side effects caused by these agents is also minimal hence their benefits.

When acoustic pressures are high above 1 MpA the u-bubbles are usually destroyed as they produce strong but short echoes.  It is also managed with the aid of transient imaging and sometimes is combined with harmonic imaging. It is also used for imaging of liver parenchyma and renal cortex (Marelli 1999, 344). Though these techniques have been proven to function, further investigation is required to establish their functionality in human beings; most of the USCA are also still suppressed for more inquiries about their effectiveness. USCA are also used or applicable in vascular diagnosis. They are effective in differentiating sub-occlusion from occlusion in the carotid artery diseases, evaluation of intracranial cerebral arteries, improvement in the detection of intracranial occlusion and stenosis (Cosgrove and Harvey 2009, 813). It also improves the level of detection of circles of Willis, and in indication of severe stenosis on internal carotid artery.  USCA is also essential in the detection of arterieovenous malformations and any cases of abnormal blood flow in the brain tumors (Dong, Ke, Yun-Hua , Kai-Bin, and Zheng 2010, 288). USCA further have been found essential in detecting blood flow in cases of attenuations   brought by calcifications or prosthetic walls.

USCA have also been found to be necesray and applicable in kidney and liver diagnosis especially in the renal artery stenosis, which is one of the major disorders that affect the kidney and the liver. USCA is usually used together with the renal color Doppler because it is cost effective and time effective test.  USCA is also essential as it gives better signs and signals in case the person is suffering from fistulas and renal tumors. Cauterization of small masses is difficult to identify using normal ultrasonography and therefore, this detection is enhanced through the aid of USCA with power mode.  Portal venous flows are also reduced because of liver atrophy and USCA helps to increase Doppler signal of blood flow in the portal vein. It also helps to reduce blooming effects (Shiba et al 2004, 12). It is also used and is useful in detection of slow blood flow organs such as testis, can be injected in the uterus to investigate or study the fallopian tubes and can be used in detection of vesico-renal reflux through the use of  levovist.

 In inclusion, the USCA has impacted greatly on the molecular imagining procedures and in the process improving the level of health care. Use of USCA has proved to produce positive results compared to other conventional techniques of ultrasound techniques. These agents even though are non-toxic there are some challenges that are manifest especially in the development of various image techniques and agents that have greater stability. However, the developments achieved are so far positive.


Correas, J.M, Bridal, L, Lesavre, A, Mejean, A, Claudon, M, Helenon, O. 2001. “Ultrasound        contrast agents: properties, principles of action, tolerance, and artifacts.” Eur Radiol           11(8):1316-28.

Cosgrove, David, and Harvey Chris. 2009. “Clinical uses of microbubbles in diagnosis and          treatment.” Medical & Biological Engineering & Computing. 47(8): 813-826.

Dong, Wang, Ke, Yang, Yun-Hua, Gao, Kai-Bin, Tan, and Zheng Liu. 2010. ‘Preparation and             characterization of a nanoscale ultrasound contrast agent.’ Clinical Imaging 34:288-292.

Duvshani-Eshet, M, and Machluf, M. 2007. “Efficient transfection of tumors facilitated by long-  term therapeutic ultrasound in combination with contrast agent: from in vitro to in vivo             setting.(Original Article).” In: Cancer Gene Therapy 14(3): 306; Nature Publishing Group Language: English

Jakobsen, J.A. 2001. “Ultrasound contrast agents: Clinical applications.”  Euro Radio. 11(8):       1329-   37. < http://www.ncbi.nlm.nih.gov/pubmed/11519539 >

Marelli, C. 1999. “Preliminary experience with NC100100, a new ultrasound contrast agent for    intravenous injection.”  European Journal of Pediatrics.Supplement 158: S343-S346.

Shiba, Josepha, Thomas, Marten ,Arnold, Gronewoldb, Marc, Dominic, Schlensogb, Carsten

            Olbricha, Eckhard, Quandtb, Michael, Famulokb, and Michael Schirnera. 2004. “Specific             targeting of ultrasound contrast agent (USCA) for diagnostic application: an in vitro         feasibility study based on SAW biosensor.” Biosensors and bioelectronics 20: 1829-  1835.

Wood et al. 2012. ‘Effects of ultrasound and ultrasound contrast agent on vascular tissue.’             Cardiovascular Ultrasound 10: 1-10.