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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">abcic</journal-id>
<journal-title-group>
<journal-title>ABC Imagem Cardiovascular</journal-title>
<abbrev-journal-title abbrev-type="publisher">ABC Imagem Cardiovasc.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2675-312X</issn>
<issn pub-type="ppub">2318-8219</issn>
<publisher>
<publisher-name>Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiolodia (DIC/SBC)</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.36660/abcimg.20250061i</article-id>
<article-id pub-id-type="publisher-id">abcimg.20250061i</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>My approach to optimize my equipment for the use of ultrasound contrast agents</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0001-6110-2500</contrib-id>
<name><surname>Lima</surname><given-names>Marcio S. M.</given-names></name>
<role>Conception and design of the research</role>
<role>Acquisition of data</role>
<role>Analysis and interpretation of the data</role>
<role>Statistical analysis</role>
<role>Writing of the manuscript</role>
<role>Critical revision of the manuscript for intellectual content</role>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c1"/>
</contrib>
<aff id="aff1">
<label>1</label>
<institution content-type="orgname">Faculdade de Medicina da Universidade de São Paulo</institution>
<institution content-type="orgdiv1">Instituto do Coração</institution>
<addr-line>
<named-content content-type="city">São Paulo</named-content>
<named-content content-type="state">SP</named-content>
</addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brazil</institution>
</aff>
<aff id="aff2">
<label>2</label>
<institution content-type="orgname">Grupo Fleury</institution>
<addr-line>
<named-content content-type="city">São Paulo</named-content>
<named-content content-type="state">SP</named-content>
</addr-line>
<country country="BR">Brazil</country>
<institution content-type="original">Grupo Fleury, São Paulo, SP – Brazil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1"><label>Mailing Address:</label> <bold>Marcio S. M. Lima</bold> • Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Av. Dr. Eneas de Carvalho Aguiar, 44. Postal Code: <postal-code>05403-000</postal-code>, São Paulo, SP – Brazil E-mail: <email>marcio.lima@incor.usp.br</email></corresp>
<fn fn-type="coi-statement"><label>Potential conflict of interest</label>
<p>I declare no relevant conflict of interest.</p></fn>
<fn fn-type="edited-by"><label>Editor responsible for the review:</label> <p>Marcelo Tavares</p></fn>
</author-notes>
<pub-date publication-format="electronic" date-type="pub">
<day>17</day>
<month>11</month>
<year>2025</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2025</year>
</pub-date>
<volume>38</volume>
<issue>3</issue>
<elocation-id>e20250061</elocation-id>
<history>
<date date-type="received">
<day>17</day>
<month>08</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>29</day>
<month>08</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>29</day>
<month>08</month>
<year>2025</year>
</date>
</history>
<permissions>
<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
</license>
</permissions>
<abstract>
<title>Abstract</title>
<p>Contrast echocardiography, based on ultrasound contrast agents composed of microbubbles, has been increasingly incorporated into echocardiography labs. It involves the infusion of compounds that enhance the visualization of various cardiac and vascular structures. The multiple adjustments required are usually included in pre-configured packages (presets) installed by manufacturers on the equipment. However, it is possible – and sometimes necessary – to make modifications to optimize image generation and, guided by the objective of the echocardiographic study, to achieve the full potential this technique can offer.</p>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Echocardiography</kwd>
<kwd>Contrast Media</kwd>
<kwd>Diagnostic Equipment</kwd>
</kwd-group>
<funding-group>
<funding-statement>This study had no external funding sources</funding-statement>
</funding-group>
<counts>
<fig-count count="14"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="13"/>
</counts>
</article-meta>
</front>
<body>
<fig id="f7">
<caption>
<title>Resonance of microbubbles in response to the energy transmitted by the echocardiography equipment transducer.</title>
<p>MI: mechanical index.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf07.tif"/>
</fig>
<sec sec-type="intro">
<title>Introduction</title>
<p>Contrast echocardiography (CE) is based on the use of ultrasound contrast agents (UCAs), or echocardiographic contrast, for the purpose of opacifying cardiac structures. It is a safe, cost-effective technique that significantly aids the diagnostic process and, consequently, guides treatment, improving patient outcomes across various clinical scenarios.<sup><xref ref-type="bibr" rid="B1">1</xref>–<xref ref-type="bibr" rid="B4">4</xref></sup></p>
<p>In this advanced echocardiographic technique, microbubble-based compounds are used – microspheres composed of high molecular weight gas (perfluorocarbon or sulfur hexafluoride) encapsulated by an albumin or lipid shell. In addition to being smaller than red blood cells, this composition gives microbubbles some unique properties. For example, they have lower solubility and diffusibility in blood, meaning greater compound stability, which allows them to cross the pulmonary capillary barrier.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Another very important aspect is the rheology of the microbubble when interacting with ultrasound (US) waves. Depending on the amount of transmitted energy, there may be linear or nonlinear radial oscillation, or even microbubble destruction. Therefore, energy adjustment is crucial in CE (Central Figure).</p>
<p>The opacification of structures occurs through the interaction between US waves and microbubbles, generating a powerful reflected signal – approximately 135 times stronger – that is captured by the echocardiography equipment. At this stage, to maximize the effectiveness of the technique, it is essential to optimize the settings of the device being used. The multiple adjustments required are typically included in preconfigured packages provided by manufacturers (presets), and the main variable is the transmitted energy, measured by the so-called Mechanical Index (MI). This adjustment should be guided primarily by the specific objective of the echocardiographic examination being performed.</p>
<sec>
<title>Ultrasound Contrast Agents and Contrast Echocardiography</title>
<p>The main and most frequent indications for the use of UCAs are:</p>
<list list-type="simple">
<list-item><label>–</label> <p>Poor acoustic image quality: the use of UCAs can &quot;rescue&quot; exams that would otherwise require additional, more complex and costly imaging methods (<xref ref-type="fig" rid="f1">Figure 1</xref>);<sup><xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B8">8</xref></sup></p></list-item>
<list-item><label>–</label> <p>Volume quantification and assessment of left ventricular (LV) systolic function: This estimation shows excellent correlation with cardiac magnetic resonance imaging, improving interobserver reproducibility (<xref ref-type="fig" rid="f2">Figure 2</xref>);<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup></p></list-item>
<list-item><label>–</label> <p>Optimization of Doppler signal for evaluating valvular gradients and estimating pulmonary artery systolic pressure;</p></list-item>
<list-item><label>–</label> <p>Stress echocardiography: enhances the analysis of segmental wall motion and allows for myocardial perfusion assessment (<xref ref-type="fig" rid="f3">Figure 3</xref>);</p></list-item>
<list-item><label>–</label> <p>Investigation of thrombi and evaluation of cardiac masses;</p></list-item>
<list-item><label>–</label> <p>Detection of LV rupture;</p></list-item>
<list-item><label>–</label> <p>Area delimitation during septal alcoholization for hypertrophic cardiomyopathy.</p></list-item>
</list>
<fig id="f1">
<label>Figure 1</label>
<caption>
<title>Patient with chronic obstructive pulmonary disease and obesity referred for a pharmacological stress echocardiogram using dobutamine.</title>
<p>Baseline imaging showed reduced quality. Improvement was observed with the use of an ultrasound contrast agent, allowing the exam to be successfully performed.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf01.tif"/>
</fig>
<fig id="f2">
<label>Figure 2</label>
<caption>
<title>Clearer visualization of the borders allows a more accurate measurement of left ventricular volumes and calculation of ejection fraction, reducing interobserver variability.</title>
<p>LV: left ventricle; RV: right ventricle.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf02.tif"/>
</fig>
<fig id="f3">
<label>Figure 3</label>
<caption>
<title>A 60-year-old woman underwent contrast echocardiography under pharmacological stress with dobutamine.</title>
<p>She experienced chest discomfort and ST-segment depression in the precordial leads on the electrocardiogram. An area of myocardial perfusion deficit was observed at the apex of the left ventricle, associated with localized hypokinesia (arrows). The test was positive for the presence of myocardial ischemia. LV: left ventricle; RV: right ventricle.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf03.tif"/>
</fig>
<p>There are numerous benefits to using UCAs in echocardiographic examinations. Some of the main advantages include:</p>
<list list-type="simple">
<list-item><label>–</label> <p>They are safe and cost-effective;</p></list-item>
<list-item><label>–</label> <p>Administration is relatively simple and quick;</p></list-item>
<list-item><label>–</label> <p>They are non-nephrotoxic;</p></list-item>
<list-item><label>–</label> <p>They do not accumulate in various tissues;</p></list-item>
<list-item><label>–</label> <p>They are associated with improved diagnostic accuracy in multiple clinical scenarios and better outcomes in critically ill patients.</p></list-item>
</list>
<p>Although relatively straightforward, certain steps are essential for the proper administration of UCAs. The key steps are outlined below:</p>
<list list-type="order">
<list-item><p>A peripheral venous access should be obtained, preferably in the antecubital fossa, with a gauge of at least 20G, along with the installation of a three-way stopcock. This access must be tested for patency to ensure proper infusion.</p></list-item>
<list-item><p>The UCA should be prepared according to the manufacturer&apos;s specifications. Sonovue, an agent approved by ANVISA and authorized for routine use in Brazil, consists of a kit containing a vial with lyophilized microbubbles of sulfur hexafluoride at a concentration of 8 μL/mL and a syringe with a 0.9% sodium chloride diluent solution. After dilution, the compound should be manually and gently homogenized.</p></list-item>
<list-item><p>Sonovue can be administered in small boluses or, much less frequently, via continuous infusion. Bolus doses typically range from 0.5 to 1.0 mL, followed by a 5 mL flush of 0.9% saline infused over 5 to 10 seconds, or by elevating the limb. It is recommended to use the smallest bolus that ensures adequate opacification, thereby conserving contrast for the entire echocardiographic study. Optimal contrast of the left ventricle is achieved when the cavity is well opacified and the endocardial-cavity interface (endocardial border) is clearly defined. Administering an excessive dose of the contrast agent may result in a &quot;blooming&quot; artifact – an intense apical brightness that distorts adjacent structures – and acoustic shadowing with image attenuation in the basal segments. Conversely, using a lower dose may lead to suboptimal contrast in the apical region, producing a &quot;swirling&quot; appearance, as well as myocardial attenuation that may be generalized or segmental, mimicking perfusion defects.</p></list-item>
</list>
</sec>
<sec>
<title>Optimizing my equipment for contrast echocardiography</title>
<p>The rheology of microbubbles and the high reflectivity of US waves are the core of the image opacification technique in CE. The structural composition of the microsphere leads to different bubble behaviors when interacting with US beams at varying levels of transmitted energy.</p>
<p>The MI is a measure that expresses the energy transmitted to tissues, <italic>i.e</italic>., the acoustic power. Conceptually, it corresponds to the peak negative pressure of the US wave divided by the square root of the central frequency (P- /√ƒ), and it is typically greater than 0.8 in most non-contrast images. This is the primary parameter to be adjusted in CE. A very low MI (&lt; 0.2) causes asymmetric and nonlinear radial oscillation of the microbubbles, characterized by greater expansion during the rarefaction phase of the US wave compared to compression at the peak acoustic pressure. This phenomenon is highly relevant in CE, as it not only reflects the fundamental frequency of the US beam transmitted by the transducer but also generates multiple harmonic frequencies – especially the second harmonic.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> The resulting signal is intense and forms the basis of image opacification in CE. Simultaneously, CE equipment is equipped with specific image cancellation algorithms that filter the received signals. Two of the most common technologies for this purpose are pulse amplitude modulation and pulse inversion, the latter illustrated in <xref ref-type="fig" rid="f4">Figure 4</xref>.</p>
<fig id="f4">
<label>Figure 4</label>
<caption>
<title>Pulse inversion algorithm for image cancellation.</title>
<p>Two ultrasound pulses are emitted at the fundamental frequency, one normal and one inverted. Top panel: In tissue, these pulses are reflected similarly (linear reflection). Subtracting the received pulses results in a null signal (no output), leading to image cancellation and reduced brightness in that sector. Bottom panel: The pulses are reflected by microbubbles at both the fundamental and harmonic frequencies. Subtracting these reflected pulses removes the fundamental frequency, resulting in a &quot;pure&quot; harmonic signal, which appears as a bright intensity in the image.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf04.tif"/>
</fig>
<p>Another important point is that with the low amount of transmitted energy, there is minimal destruction of microbubbles within the myocardial microvasculature. This allows not only enhanced visualization of the LV cavity but also for the assessment of myocardial perfusion (MP). Following the recommendation to use imaging in fundamental mode (although harmonic mode may also be used), with a very low Mechanical Index (MI &lt; 0.2), an excellent contrast-to-noise ratio is achieved, along with clear delineation of the interface between the myocardium and the LV cavity (endocardial borders), as well as the ability to evaluate MP. Therefore, setting a very low MI (&lt; 0.20) combined with image cancellation algorithm technology represents the optimal parameters for assessing volumes, ejection fraction, segmental contraction, and MP – even in real time, both at rest and under stress.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B11">11</xref>–<xref ref-type="bibr" rid="B13">13</xref></sup></p>
<p>Specifically for the assessment of MP, the use of high-energy pulse &quot;flashes&quot; (MI: 0.8–1.2; 5–15 frames) is recommended to destroy microbubbles within the myocardium while preserving opacification within the cardiac chamber. The replenishment time should be less than five seconds at rest and less than two seconds under stress. Typically, this function is already included in the equipment&apos;s preset and can be easily activated.</p>
<p>Intermediate MI levels (0.2–0.5) may be used, offering improved image resolution, though at the cost of increased microbubble destruction. MI values above 0.5 should not be used in CE. Situations where this energy level may be appropriate include the investigation of thrombi and masses, as well as the diagnosis of non-compacted cardiomyopathy.</p>
<p>Regarding image generation technology, although harmonic imaging is currently available in CE transducers, the use of nonlinear fundamental frequency is recommended. This approach ensures a better contrast-to-noise ratio, with the frame rate adjusted to approximately 25–35 Hz and the transducer transmission frequency kept below 2.0 MHz.</p>
<p>In patients with a larger body surface area, it may be necessary to adjust to an even lower transmission frequency to allow greater penetration of the ultrasound beam into the tissues. It is possible to use either grayscale imaging or apply color mapping (&quot;chroma&quot;), such as red ruby, to the generated images.</p>
<p>Image depth should be adjusted according to the objective of the examination. If the focus is on LV opacification for volume quantification, systolic function assessment, and delineation of endocardial borders for segmental contraction analysis, the image depth should be set to visualize the mitral valve and approximately 1 to 2 cm of the left atrium.</p>
<p>Image attenuation in the basal segments of the LV may occur, especially when an excessive amount of UCA is used. This can lead to a misdiagnosis of perfusion deficits in these regions. Some strategies can be adopted to improve image definition, such as centering the basal segments in the image – since axial resolution is superior to lateral resolution in the ultrasound field – positioning the focus at the level of the mitral valve, and increasing the gain in this area using the time gain compensation adjustment. An example of these adjustments is illustrated in <xref ref-type="fig" rid="f5">Figure 5</xref>.</p>
<fig id="f5">
<label>Figure 5</label>
<caption>
<title>Contrast echocardiography.</title>
<p>Recommended adjustments to optimize this image include: positioning the focus (yellow arrow) at the level of the mitral valve to improve acoustic resolution of the basal segments and reducing the gain to enhance delineation of the endocardial borders. LV: left ventricle; RV: right ventricle.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf05.tif"/>
</fig>
<p>If the goal is to investigate a possible apical thrombus, non-compacted cardiomyopathy, or evaluate an apical aneurysm (<xref ref-type="fig" rid="f6">Figure 6</xref>), it is necessary to reduce the image depth and adjust the focus to that specific region. Setting the Mechanical Index (MI) to an intermediate level (2.0–3.0) may help improve spatial resolution, although this comes at the cost of increased microbubble destruction.</p>
<fig id="f6">
<label>Figure 6</label>
<caption>
<title>Apical aneurysm image better visualized with the use of an ultrasound contrast agent, allowing clear definition of the endocardial borders and more accurate measurement.</title>
<p>LV: left ventricle; RV: right ventricle.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf06.tif"/>
</fig>
<p>Attenuation may also occur in the myocardium of the apical region of the left ventricle, due to higher acoustic power in that area and, occasionally, a higher frame rate, which leads to greater microbubble destruction. Recommended adjustments to optimize the image in these cases include reducing the frame rate and adjusting the gain locally.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
<p>Finally, UCAs can also be used to assist in estimating valvular gradients and systolic pressure in the pulmonary artery. In such cases, the signal (and noise) generated may be intense. The recommendation is to reduce the gain until clear spectral curves with well-defined envelopes are obtained.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
</sec>
</sec>
<sec sec-type="conclusions">
<title>Conclusion</title>
<p>CE, based on the opacification of cardiac structures using UCAs composed of microbubbles, has been increasingly adopted across various echocardiography labs. This procedure offers numerous benefits, but to fully achieve its potential, certain equipment adjustments are necessary. Typically, adjustment packages (presets) come pre-configured and installed by manufacturers, and their use is recommended. The primary adjustment involves the level of energy transmitted by the transducer, represented by the MI, which is crucial for minimizing microbubble destruction. This ensures proper opacification of the left ventricle and enables the assessment of MP. Other recommended adjustments include place the image focus at the level of the mitral valve, modifying overall and/or sectoral gain to enhance visualization of apical and basal segments, reducing the frame rate, adjusting the US beam depth, and selecting either fundamental or harmonic imaging modes for image generation.</p>
</sec>
</body>
<back>
<fn-group>
<fn fn-type="financial-disclosure" id="fn1"><label>Sources of funding</label>
<p>This study had no external funding sources</p></fn>
<fn fn-type="other" id="fn2"><label>Study association</label>
<p>This study is not affiliated with any graduate programs.</p></fn>
<fn fn-type="other" id="fn3"><label>Ethics approval and consent to participate</label>
<p>This article does not contain any studies with human or animal subjects performed by any of the authors.</p></fn>
<fn fn-type="other" id="fn4"><label>Use of Artificial Intelligence</label>
<p>The authors did not use artificial intelligence tools in the development of this work.</p></fn>
</fn-group>
<sec sec-type="data-availability" specific-use="data-in-article">
<label>Data Availability</label>
<p>The underlying content of the research text is contained in the manuscript.</p>
</sec>
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<sub-article article-type="translation" id="S1" xml:lang="pt">
<front-stub>
<article-id pub-id-type="doi">10.36660/abcimg.20250061</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Artigo de Revisão</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Como eu Faço para Otimizar meu Equipamento para o Uso dos Agentes de Realce Ultrassonográfico</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">0000-0001-6110-2500</contrib-id>
<name><surname>Lima</surname><given-names>Marcio S. M.</given-names></name>
<role>Concepção e desenho da pesquisa</role>
<role>Obtenção de dados</role>
<role>Análise e interpretação dos dados</role>
<role>Análise estatística</role>
<role>Redação do manuscrito</role>
<role>Revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
<xref ref-type="aff" rid="aff3"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff4"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c2"/>
</contrib>
<aff id="aff3">
<label>1</label>
<addr-line>
<named-content content-type="city">São Paulo</named-content>
<named-content content-type="state">SP</named-content>
</addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP – Brasil</institution>
</aff>
<aff id="aff4">
<label>2</label>
<addr-line>
<named-content content-type="city">São Paulo</named-content>
<named-content content-type="state">SP</named-content>
</addr-line>
<country country="BR">Brasil</country>
<institution content-type="original">Grupo Fleury, São Paulo, SP – Brasil</institution>
</aff>
</contrib-group>
<author-notes>
<corresp id="c2"><label>Correspondência:</label> <bold>Marcio S. M. Lima</bold> • Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Av. Dr. Eneas de Carvalho Aguiar, 44. CEP: <postal-code>05403-000</postal-code>, São Paulo, SP – Brasil E-mail: <email>marcio.lima@incor.usp.br</email></corresp>
<fn fn-type="edited-by"><label>Editor responsável pela revisão:</label> <p>Marcelo Tavares</p></fn>
<fn fn-type="coi-statement"><label>Potencial conflito de interesse</label>
<p>Declaro não haver conflito de interesses pertinentes.</p></fn>
</author-notes>
<abstract>
<title>Resumo</title>
<p>A ecocardiografia contrastada, fundamentada nos agentes de realce ultrassonográfico à base de microbolhas, tem sido cada vez mais incorporada aos serviços de ecocardiografia. Essa técnica consiste na infusão de compostos que realçam as diversas estruturas cardíacas e vasculares. Os múltiplos ajustes necessários geralmente fazem parte de pacotes pré-configurados (<italic>presets</italic>) instalados nos equipamentos pelos fabricantes. Contudo, é possível, e às vezes necessário, realizar modificações para otimizar a geração das imagens e, conforme o objetivo do estudo ecocardiográfico, obter o máximo desempenho que essa técnica pode oferecer.</p>
</abstract>
<kwd-group xml:lang="pt">
<title>Palavras-chave</title>
<kwd>Ecocardiografia Contrastada</kwd>
<kwd>Agentes de Reace Ultrassonográfico</kwd>
</kwd-group>
<funding-group>
<funding-statement>O presente estudo não teve fontes de financiamento externas</funding-statement>
</funding-group>
</front-stub>
<body>
<fig id="f14">
<caption>
<title>Ressonância das microbolhas em resposta à energia transmitida pelo transdutor do equipamento de ecocardiograma.</title>
<p>IM: índice mecânico.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf07-pt.tif"/>
</fig>
<sec sec-type="intro">
<title>Introdução</title>
<p>A Ecocardiografia Contrastada (EC) baseia-se no uso de agentes de realce ultrassonográfico (ARUs), ou contraste ecocardiográfico, para fins de opacificação de estruturas. Trata-se de uma técnica segura, custo-efetiva, que auxilia de forma significativa o processo diagnóstico e, em consequência, a condução do tratamento, melhorando a evolução dos pacientes nos diversos cenários clínicos.<sup><xref ref-type="bibr" rid="B1">1</xref>–<xref ref-type="bibr" rid="B4">4</xref></sup></p>
<p>Nesta técnica avançada da ecocardiografia, são utilizados compostos a base de microbolhas, que se tratam de microesferas constituídas por gás de alto peso molecular (perfluorocarbono ou hexafluoreto de enxofre) encapsuladas por um invólucro de albumina ou lipídio. Além das microbolhas possuírem um tamanho inferior em comparação às hemácias, essa composição lhe confere alguns aspectos peculiares. Por exemplo, uma menor solubilidade e difusibilidade no sangue, ou seja, maior estabilidade do composto, o que permite atravessar a barreira capilar pulmonar.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> Um outro aspecto muito importante é a reologia da microbolha quando em interação com as ondas de ultrassom (USG). A depender da quantidade de energia transmitida, haverá desde oscilação radial linear, não linear, até a destruição da microbolha. Desta forma, este ajuste é crucial na EC (Figura Central).</p>
<p>A opacificação das estruturas ocorre pela interação das ondas de USG com as microbolhas, gerando um potente sinal refletido (de aproximadamente 135 vezes) a ser captado pelo equipamento de ecocardiograma. Neste ponto, com a finalidade de se obter o máximo desta técnica, é de suma importância um ajuste otimizado do aparelho utilizado. Os múltiplos ajustes necessários geralmente fazem parte de pacotes já montados pelos fabricantes (<italic>presets</italic>), e a principal variável é a energia transmitida, medida pelo chamado Índice Mecânico (IM). Esse ajuste deve ser balizado principalmente pelo objetivo do exame ecocardiográfico que está sendo realizado.</p>
<sec>
<title>Agentes de realce ultrassonográfico e ecocardiografia contrastada</title>
<p>As principais e mais frequentes indicações para o uso dos ARUs são:</p>
<list list-type="simple">
<list-item><label>–</label> <p>Imagem acústica com qualidade ruim. O uso dos ARUs pode &quot;salvar&quot; exames que teoricamente poderiam levar a novas solicitações de outros métodos mais complexos e onerosos (<xref ref-type="fig" rid="f8">Figura 1</xref>);<sup><xref ref-type="bibr" rid="B6">6</xref>–<xref ref-type="bibr" rid="B8">8</xref></sup></p></list-item>
<list-item><label>–</label> <p>Quantificação de volumes e avaliação da função sistólica do Ventrículo Esquerdo (VE). Esta estimativa tem excelente correlação com a ressonância magnética cardíaca, aumentando a reprodutibilidade interobservador (<xref ref-type="fig" rid="f9">Figura 2</xref>);<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup></p></list-item>
<list-item><label>–</label> <p>Otimização do sinal Doppler para avaliação de gradientes valvares e estimativa da pressão sistólica na artéria pulmonar;</p></list-item>
<list-item><label>–</label> <p>Ecocardiografia sob estresse: otimiza a análise da motilidade segmentar e permite avaliar a perfusão miocárdica (<xref ref-type="fig" rid="f10">Figura 3</xref>);</p></list-item>
<list-item><label>–</label> <p>Pesquisa de trombos e avaliação de massas cardíacas;</p></list-item>
<list-item><label>–</label> <p>Pesquisa de rotura do VE;</p></list-item>
<list-item><label>–</label> <p>Delimitação de área na alcoolização septal da cardiomiopatia hipertrófica.</p></list-item>
</list>
<fig id="f8">
<label>Figura 1</label>
<caption>
<title>Paciente portador de doença pulmonar obstrutiva crônica e obesidade com solicitação de ecocardiograma farmacológico sob estresse pela dobutamina.</title>
<p>Imagem basal com qualidade reduzida. Houve melhora com o uso do agente de realce de ultrassom possibilitando a realização do exame.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf01-pt.tif"/>
</fig>
<fig id="f9">
<label>Figura 2</label>
<caption>
<title>A visibilização mais nítida dos bordos possibilita uma medida mais acurada dos volumes do ventrículo esquerdo e cálculo da fração de ejeção, reduzindo a variabilidade interobservador.</title>
<p>VE: ventrículo esquerdo; VD: ventrículo direito.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf02-pt.tif"/>
</fig>
<fig id="f10">
<label>Figura 3</label>
<caption>
<title>Mulher de 60 anos submetida à ecocardiografia contrastada sob estresse farmacológico pela dobutamina.</title>
<p>Apresentou desconforto torácico e infradesnivelamento do segmento ST em derivações precordiais no traçado eletrocardiográfico. Observou-se área com déficit de perfusão miocárdica no ápice do ventrículo esquerdo associada à hipocinesia local (setas). Teste positivo para presença de isquemia miocárdica. VE: ventrículo esquerdo; VD: ventrículo direito.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf03-pt.tif"/>
</fig>
<p>São muitos os benefícios do uso dos ARUs no exame ecocardiográfico. Seguem alguns listados abaixo:</p>
<list list-type="simple">
<list-item><label>–</label> <p>São seguros e custo-efetivos;</p></list-item>
<list-item><label>–</label> <p>Têm administração relativamente simples e rápida;</p></list-item>
<list-item><label>–</label> <p>Não são nefrotóxicos;</p></list-item>
<list-item><label>–</label> <p>Não depositam nos diversos tecidos;</p></list-item>
<list-item><label>–</label> <p>Estão associados a uma melhor definição diagnóstica em múltiplos cenários e a melhor evolução em pacientes críticos.</p></list-item>
</list>
<p>Embora relativamente simples, alguns passos são essenciais para a administração dos ARUs. Os principais são aqui mencionados:</p>
<list list-type="order">
<list-item><p>Deve ser obtido um acesso venoso periférico de preferência na fossa antecubital, com calibre de pelo menos 20G, associado à instalação de uma torneira de três vias. Esse acesso deve ter a sua patência testada para garantir uma boa infusão;</p></list-item>
<list-item><p>Preparo do ARU conforme especificação do fabricante. O Sonovue, agente aprovado pela ANVISA e liberado para uso rotineiro no Brasil, consiste em um kit contendo basicamente um frasco-ampola com as microbolhas liofilizadas de hexafluoreto de enxofre numa concentração de 8μL/mL e uma seringa com diluente de solução de cloreto de sódio a 0,9%. Após a diluição, o composto deve der homogeneizado manualmente e de forma suave;</p></list-item>
<list-item><p>O Sonovue pode ser usado em pequenos <italic>bolus</italic> ou, muito menos frequentemente, em infusão contínua. Os <italic>bolus</italic> de infusão do Sonovue variam entre 0,5 e 1,0 mL, seguidos de um <italic>flush</italic> de 5 mL de SF 0,9% infundido em 5 a 10 segundos, ou pela elevação do membro. Recomenda-se usar o menor <italic>bolus</italic> possível que garanta uma boa opacificação, assim economizando para realização de todo o estudo ecocardiográfico. Um contraste ótimo do VE seria uma adequada opacificação da cavidade com nítida determinação da interface endocárdio-cavidade (bordo endocárdico). O uso de uma dose excessiva do ARU pode levar à formação do artefato de &quot;<italic>blooming&quot;</italic>, um grande brilho apical com distorção das estruturas adjacentes, e de sombra acústica com atenuação da imagem nos segmentos basais. Já a infusão de uma dose menor pode ocasionar um contraste inferior da porção apical, com aspecto &quot;em redemoinho&quot; (<italic>swirling</italic>), além de atenuação miocárdica que pode ser generalizada ou segmentar, mimetizando déficits de perfusão.</p></list-item>
</list>
</sec>
<sec>
<title>Otimizando o meu equipamento para a ecocardiografia contrastada</title>
<p>A reologia das microbolhas e a elevada capacidade refletiva das ondas de USG são o cerne da técnica de opacificação de imagem na EC. A composição estrutural da microesfera leva a diferentes comportamentos da bolha quando em interação com feixes de USG com diferentes níveis de energia transmitida.</p>
<p>O IM é uma medida que expressa a energia transmitida aos tecidos, ou seja, a potência acústica. Conceitualmente, corresponde à pressão negativa máxima da onda de USG dividida pela raiz quadrada da frequência central (P- /√ƒ), sendo superior a 0,8 na maioria das imagens sem contraste. Este é o principal parâmetro a ser ajustado na EC. Um IM muito baixo (&lt; 0,2) ocasiona uma oscilação radial assimétrica e não linear das microbolhas, caracterizada por uma expansão na fase de rarefação da onda de USG superior à compressão no pico de pressão acústica. Isso é muito importante na EC, pois além de refletir a frequência fundamental do feixe de USG transmitida pelo transdutor, gera múltiplas frequências harmônicas, em especial a segunda harmônica.<sup><xref ref-type="bibr" rid="B5">5</xref></sup> O sinal gerado é intenso, sendo a base da opacificação da EC. Ao mesmo tempo, os equipamentos na EC são dotados de algoritmos específicos de cancelamento de imagem, que filtram os sinais recebidos. Duas das tecnologias mais usadas para esse fim são a modulação de amplitude de pulso e a inversão de pulso, exemplificada na <xref ref-type="fig" rid="f11">Figura 4</xref>.</p>
<fig id="f11">
<label>Figura 4</label>
<caption>
<title>Algoritmo de pulso invertido para cancelamento de imagem.</title>
<p>Dois pulsos de ultrassom são emitidos na frequência fundamental, um normal e outro invertido. Acima: nos tecidos eles serão refletidos de forma semelhante (reflexão linear). A subtração destes pulsos recebidos tem a resultante nula (sem sinal), levando ao cancelamento (imagem com menor brilho no setor). Abaixo: os pulsos são refletidos pelas microbolhas na frequência fundamental e em harmônicas. A subtração destes pulsos refletidos levará a &quot;retirada da frequência fundamental&quot; tendo como resultante um sinal harmônico &quot;puro&quot;, disposto na intensidade brilhante na imagem.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf04-pt.tif"/>
</fig>
<p>Outro ponto relevante é que, com a baixa quantidade de energia transmitida, ocorre pouca destruição das microbolhas dentro da microvascularização miocárdica. Isso permite, além de realçar a cavidade do VE, avaliar a perfusão miocárdica (PM). Seguindo a recomendação de usar a imagem no modo fundamental (embora o modo harmônico também possa se usado), com IM muito baixo (&lt; 0,2), obtém-se uma ótima relação sinal-ruído do contraste, com excelente delineamento da interface entre o miocárdio e a cavidade do VE (bordos endocárdicos), além da possibilidade de avaliar a PM. Assim, o ajuste para um IM muito baixo (&lt; 0,20) associado à tecnologia de algoritmos de cancelamento de imagem, são os parâmetros ótimos para se avaliar volumes, fração de ejeção, contração segmentar e PM, inclusive em tempo real, tanto no repouso quanto sob estresse.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B11">11</xref>–<xref ref-type="bibr" rid="B13">13</xref></sup></p>
<p>Especificamente para a avaliação da PM recomenda-se o uso de &quot;<italic>flashes</italic>&quot; de pulsos de alta energia (IM: 0,8-1,2; 5-15 quadros) com a finalidade de destruir as microbolhas no interior do miocárdio (preservando a opacificação dentro da cavidade cardíaca) e observar o tempo de repreenchimento que deve ser inferior a cinco segundos no repouso e a dois segundos no estresse. Normalmente, esse comando já está inserido no <italic>preset</italic> do equipamento, sendo facilmente acionado.</p>
<p>Níveis intermediários de IM (0,2-0,5) podem ser utilizados. Com isso, obtém-se maior resolução de imagem, porém à custa de maior destruição das microbolhas. Valores de IM acima de 0,5 não devem ser usados na EC. Exemplos de situações em esse nível de energia pode ser empregado são: pesquisa de trombos e massas, e no diagnóstico da miocardiopatia não compactada.</p>
<p>Com relação à tecnologia de geração de imagens, embora atualmente seja possível utilizar a harmônica nos transdutores durante a ecocardiografia contrastada (EC), recomenda-se o uso da frequência fundamental não linear. Essa abordagem garante uma melhor relação sinal-ruído do contraste na imagem, com a taxa de enquadramento (frame rate) ajustada para aproximadamente 25–35 Hz e frequência de transmissão do transdutor inferior a 2,0 MHz.</p>
<p>Em pacientes com maior superfície corpórea, pode ser necessário ajustar para uma frequência de transmissão ainda menor, a fim de permitir maior penetração do feixe de ultrassom nos tecidos. É possível utilizar tanto a imagem em escala de cinza quanto aplicar coloração (&quot;croma&quot;), como o vermelho rubi, nas imagens geradas.</p>
<p>A profundidade deve ser ajustada de acordo com o objetivo do exame. Caso o foco seja a opacificação do VE para quantificar volumes e avaliar a função sistólica e o delineamento de bordas endocárdicas para análise de contração segmentar, deve-se ajustar a profundidade da imagem para se visualizar a valva mitral e cerca de 1 a 2 cm do átrio esquerdo.</p>
<p>A atenuação da imagem nos segmentos basais do VE pode ocorrer, sobretudo quando se usa uma quantidade de ARU acima do necessário. Isso pode levar a um diagnóstico errôneo de déficit de perfusão nesses locais. Algumas estratégias podem ser adotadas para melhorar essa definição, como centralizar os segmentos basais na imagem — já que a resolução axial é superior à lateral no campo ultrassonográfico —, posicionar o foco no nível da valva mitral e aumentar o ganho nessa área por meio do ajuste do ganho setorial. Um exemplo desses ajustes está ilustrado na <xref ref-type="fig" rid="f12">Figura 5</xref>.</p>
<fig id="f12">
<label>Figura 5</label>
<caption>
<title>Ecocardiograma contrastado.</title>
<p>Ajustes recomendados para otimizar essa imagem: posicionamento do foco (seta amarela) no nível da valva mitral para melhor resolução acústica dos segmentos basais e redução do ganho para melhor delimitação das bordas endocárdicas. VE: ventrículo esquerdo; VD: ventrículo direito.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf05-pt.tif"/>
</fig>
<p>Por outro lado, se o objetivo for a pesquisa de um possível trombo apical, miocardiopatia não compactada ou avaliação de aneurisma apical (<xref ref-type="fig" rid="f13">Figura 6</xref>), é necessário reduzir a profundidade da imagem e ajustar o foco para essa região específica. O ajuste do Índice Mecânico (IM) para um nível intermediário (2,0–3,0) pode contribuir para melhorar a resolução espacial, embora isso ocorra à custa de maior destruição das microbolhas.</p>
<fig id="f13">
<label>Figura 6</label>
<caption>
<title>Imagem de aneurisma apical melhor visualizado com o uso do agente de realce ultrassonográfico, permitindo nítida definição dos bordos endocárdicos e mensuração mais acurada.</title>
<p>VE: ventrículo esquerdo; VD: ventrículo direito.</p></caption>
<graphic xlink:href="2675-312X-abcic-38-03-e20250061-gf06-pt.tif"/>
</fig>
<p>Atenuação também pode ocorrer no miocárdio da região apical do VE, devido à maior potência acústica nessa área e, eventualmente, à maior taxa de enquadramento, o que leva à destruição acentuada das microbolhas. Ajustes recomendados para otimizar a imagem nesses casos incluem a redução da taxa de enquadramento e o ajuste do ganho local.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
<p>Por fim, é possível se usar os ARUs para auxiliar na estimativa de gradientes valvares e da pressão sistólica na artéria pulmonar. Neste caso, o sinal (e ruído) gerado pode ser intenso. A recomendação é reduzir o ganho até que se obtenha obter curvas espectrais com envelopes nítidos.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
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<title>Conclusão</title>
<p>A EC, fundamentada na opacificação das estruturas cardíacas por meio do uso dos ARU por microbolhas, tem sido cada vez mais incorporada nos diversos serviços de ecocardiografia. São muitos os benefícios desse procedimento, mas para se obter o máximo que essa técnica pode oferecer, alguns ajustes do equipamento são necessários. Habitualmente, os pacotes (<italic>presets</italic>) de ajustes já vêm montados e instalados pelos fabricantes nos equipamentos, sendo recomendado utilizá-los. O principal ajuste é o nível de energia transmitida pelo transdutor, representado pelo IM, importante para reduzir a destruição das microbolhas. Isto possibilita uma adequada opacificação do VE e a avaliação da PM. Outros ajustes incluem o posicionamento do foco para o nível da valva mitral, a modificação do ganho geral e/ou setorial para melhorar a visualização dos segmentos apicais e basais, a redução da taxa de enquadramento, o ajuste da profundidade do feixe de ultrassom e o uso do modo fundamental ou harmônico para geração da imagem.</p>
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