ABC | Volume 112, Nº6, June 2019

Statement Vascular Ultrasound Statement from the Department of Cardiovascular Imaging of the Brazilian Society of Cardiology – 2019 Arq Bras Cardiol. 2019; 112(6):809-849 The creation of each “specific microbubble” signal requires proper interaction between signals of the microbubble contrast agent and the insonated US beam. 8.1. Properties of Ultrasound Contrast Agents Unlike contrasts for magnetic resonance imaging (MRI) and computed tomography, which use physical and chemical characteristics of cells to generate their effect, microbubble contrast uses the physical attributes of US, that is, the higher the density difference between media, the greater the reflection of energy emitted and larger the amplitude of US signal. Unquestionably, the gaseous medium provides the greatest difference, corresponding to a signal increase of approximately 30 decibels. US contrast agents are microbubbles of gas inside capsules with flexible and stable phospholipid membranes and a defined size. The SonoVue® 127 agent (produced by Bracco Imaging S.p.A., Milan, Italy), sold in Europe, the United States, parts of Asia, and South America, is the only product currently authorized in Brazil by the Brazilian Health Regulatory Agency ( Agência Nacional de Vigilância Sanitária – Anvisa) and members of the National Regulatory Agency for Private Health Insurance and Plans ( Agência Nacional de Saúde Suplementar – ANS). SonoVue® consists of encapsulated microspheres of sulfur hexafluoride gas. Microbubbles have an average diameter of 2.3 µm (a size that prevents them from crossing blood vessel walls and reaching the interstitial space). As a lipophilic gas, its solubility in blood is low, and it does not spread outside the capsule. This protein shell composed of a single layer of phospholipids acts as a surfactant, giving it stability and flexibility along its path in the blood macro- and microcirculation. Therefore, SonoVue® is considered an integral agent of the blood pool and a marker of blood circulation (property that distinguishes it from contrasts used in MRI and computed tomography, which can cross into the extracellular space). After the microbubble bursts, the gas is almost entirely exhaled through the lungs during respiration, without undergoing liver metabolism or renal excretion. 124 Thus, there is no contraindication to its use in patients with renal failure. 8.2. Technical Aspects that Influence the Acquisition of Contrast Images Currently, most US manufacturers have exclusive software for studies with contrast, which can be included in the original configuration of the machine or purchased separately. However, even equipment without a specific image component for contrast has some parameters the operator can configure. The following concepts and adjustments of the equipment must be known to get the best result during the contrast study: 8.2.1. Mechanical Index A unique characteristic of contrast agents for US (non- existent in those used for MRI and computed tomography) is that they are modified by the waves used to detect them. When exposed to US, microbubble behavior changes according to the US power emitted, that is, the amplitude of the acoustic wave [called mechanical index (MI) in the equipment]. In non-contrast studies, MI ranges from 1.6 to 1.9; under this acoustic power, the microbubble always oscillates vigorously and bursts, causing two unwanted effects: a sudden increase in signal intensity with an excessive blurring of the image, and a significant reduction in contrast concentration, consequently shortening the examination time. This image mode, called “image by acoustic stimulation,” does not require equipment with contrast technology (but, on the other hand, it does not use the full potential of the contrast agent, limiting it to its echo-enhancer function). After reducing MI to ≤ 0.1, we can not only keep the integrity of microbubbles but also make them oscillate non- linearly (initial compression followed by expansion) and resonate, emitting different frequencies (known as “harmonic frequencies”) from the fundamental one emitted by the transducer. Equipment with this technology can filter signals emitted specifically by microbubbles, leading to a more lasting study that highlights microbubble over tissue signal (virtually nulled in the image, appearing as a dark background). This type of study, also called “contrast study with low MI”, allows the examiner to evaluate the contrast wash-in continuously in the local studied, the enhancement period, and the concentration of microbubbles in the target structure [essential for situations such as the study of vessels of vessels ( vasa vasorum ), carotid plaques, renal capillary (perfusion) distribution, and masses]. 124 An undesired effect of the contrast study with low MI is the depth limitation of the pulse wave, which undergoes greater attenuation as it moves through tissues. Some ways to minimize this effect are: adopting alternative acoustic windows that allow closer proximity with the structure of interest, using broadband transducers with lower frequencies, and, as a last resort, increasing the MI and consequently destroying more bubbles in the proximal field. 128 8.2.2. Image Gain A noteworthy equipment control in the contrast study is the image gain, which amplifies the signal received during the post-processing in the equipment. High gain produces a bright image and widespread increase in background noise, obscuring the contrast signal (once the saturation level of the equipment has been reached, there will be no margin to amplify the signal caused by contrast). Therefore, during the contrast study, the equipment gain should be reduced until the image is virtually black, except for highly echogenic structures. Some manufacturers have gain adjustment controls for contrast studies that can easily be turned on and off during the examination. When performing a manual adjustment, make sure to have the least amount of acoustic signals before contrast injection and understand if this signal results from an increase in MI (when specific structures are seen in the image) or gain (which causes a widespread rise in noise across the image). 6 8.2.3. Contrast Level A last technical aspect worth mentioning is the dose of contrast injected. High doses initially blur (saturation) the 842