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Ultrasound contrast physics: a series on contrast echocardiography, article 3

Ultrasound contrast physics: a series on contrast echocardiography, article 3
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  959 INTRODUCTION This third article in a series on contrast echocardio-graphy addresses the physics of microbubbles.Theproperties of ultrasonographic contrast agents andthe manner in which bubbles react within an ultra-sound beam will be discussed in general.It is impor-tant to realize that the field of contrast echocardiog-raphy is changing as ultrasonographic equipmentmanufacturers modify signal processing for contrast-enhanced images;at the same time,manufacturers of contrast agents are developing new microbubbles.Therefore the sonographer will need a greater under-standing of microbubble composition,infusion tech-niques,physics,and optimal machine settings.Thisarticle serves as a primer to elucidate the interac-tions between ultrasound and ultrasonographic con-trast agents at the current level of technology. CURRENT CONTRAST AGENTS The current generation of contrast agents compris-es small,stabilized,gas-filled microbubbles that canpass through the smallest capillaries.Table 1 com-pares the size of new contrast agents to red bloodcells,agitated saline solution,and Albunex (the firstultrasonographic contrast agent approved by the USFood and Drug Administration).The larger themicrobubbles,the better the contrast effect.If they are too large,however,they get hung up in capillar-ies and are unable to cross the pulmonary circula-tion.Current microbubbles can be visualized withinthe left heart chambers after an intravenous injec-tion for two reasons:(1) they are smaller than redblood cells and so can pass through the pulmonary capillaries,and (2) they are stable,relative to timeand pressure (they can persist long enough to trav-el through the pulmonary capillary bed,and they can withstand left-sided pressures).The propertiesof an ideal contrast agent (Table 2) include nontox-icity,easy administration,stability,and responsive-ness to ultrasound interaction. Ultrasound Contrast Physics:A Series onContrast Echocardiography,Article 3 Marti McCulloch, RDCS, University of Texas Medical Branch, Galveston, Texas;Cris Gresser, RDCS, Consultant, Heart Vista, Toronto, Ontario, Canada; Sally Moos, RDCS,University of Virginia, Charlottesville, Virginia; Jill Odabashian, RDCS, The Cleveland ClinicFoundation, Cleveland, Ohio; Susan Jasper, BSN, RN, The Cleveland Clinic Foundation,Cleveland, Ohio; Jim Bednarz, RDCS, University of Chicago Hospital, Chicago, Illinois;Pam Burgess, RDCS, Wake Forest University/Baptist Medical Center, Winston-Salem,North Carolina; Dennis Carney, RCVT, Spokane Community College, Spokane, Washington; Vickie Moore, RDCS, Jewish Hospital, Cincinnati, Ohio; Eric Sisk, RDCS, Harborview MedicalCenter, Spokane, Washington; Alan Waggoner, RDCS, Washington University School of Medicine,St Louis, Missouri; Sandy Witt, RDCS, Children’s Hospital Medical Center, Cincinnati, Ohio;and David Adams, RDCS, Duke University Medical Center, Durham, North Carolina The authors gratefully acknowledge technical support for this arti-cle by DuPont Pharmaceuticals Company.The American Society of Echocardiography (ASE) is accredited by the Accreditation Council for Continuing Medical Education(ACCME) to sponsor continuing medical education for physi-cians. The ASE designated this educational activity for 1 hour of Category 1 credit of the AMA Physicians’ Recognition Award.The ASE adheres to ACCME Standards regarding industry sup-port of continuing medical education. Disclosures of faculty andcommercial sponsor relationships, if any, have been indicated. Target Audience: Participation should include individuals from the fields of cardiacsonography, cardiovascular anesthesiology, cardiovascular medi-cine, cardiovascular surgery, pediatric cardiology, neurology, andnursing, as well as medical residents/fellows, and students. Educational Objective(s): Upon completing the reading of this article the participant shouldbe able to:1.Discuss what microbubbles are and their ideal properties.2.Understand the importance of mechanical index (MI) and how to change it.3.Discuss the difference between fundamental and second har-monic imaging.4.Identify potential artifacts, such as attenuation and swirling, and how to correct them.The estimated time for this CME activity is approximately 1 hour.Reprint requests: David Adams, RDCS, Duke University MedicalCenter, Box 3818, Durham, NC 27710 (E-mail: david.adams  ).J Am Soc Echocardiogr 2000;13:959-67.Copyright © 2000 by the American Society of Echocardiography.0894-7317/2000/$12.00 + 0 27/1/107004 doi:10.1067/mje.2000.107004 CARDIAC SONOGRAPHERS’ COMMUNICATION  The ultrasonic characteristics of these contrastagents depend not only on the size of the bubblebut also on the composition of the shell and the gascontained within the shell.The outer shell of themicrobubbles is composed of many different sub-stances,including albumin,polymers,palmitic acid,or phospholipids.The composition of the shelldetermines its elasticity,its behavior in an ultrason-ic field,and the methods for metabolism and elimi-nation.In general,the stiffer the shell,the more eas-ily it will crack or break with ultrasonic energy.Conversely,the more elastic the shell,the greater itsability to be compressed or resonated and to pro-duce a nonlinear backscatter signature.The gas contained within the microbubbles iseither air or a gas of high molecular weight.Figure 1demonstrates some of the advantages and disadvan-tages of using these two different kinds of gases.Theadvantages of the air-filled microbubble are that it is astrong reflector of ultrasound and highly soluble;how-ever,the microbubble has low persistence and lacksstability because air diffuses out of it.This shrinkingmicrobubble becomes less and less reflective.Gases of high molecular weight,on the other hand,are not very soluble and so are stable and have longer persistence. Again,persistence is important in prolonging the con-trast effect so that adequate assessment of left ven-tricular borders and wall motion can be made.The major technical difficulties in using contrastagents for left ventricular opacification are the need toresonate but not burst microbubbles and to maintainadequate bubble concentration within the cavity.Technically adequate contrast studies depend on theinjection of a sufficient concentration of microbubblesand the proper ultrasonographic equipment settings tooptimize image quality.Inadequate bubble concentra-  Journal of the American Society of Echocardiography  960 McCulloch et al October 2000 tion,which results in less opacification of the chamber, was a difficulty with first-generation agents because of excessive bubble destruction when insonified with ultrasound.Left ventricular opacification is an applica-tion that requires a long duration of the contrast effectfor the assessment of left ventricular borders in subop-timal patients both in rest and under stress.Contrastagents that are more easily destroyed will probably beuseful in the future for myocardial perfusion studies. HARMONICS  All objects have an inherent or natural frequency. As an object oscillates at this natural frequency,aseries of oscillations may also be produced at mul-tiples of that natural frequency.Harmonics are alsogenerated by microbubbles when they are insoni-fied within an acoustic field.Two unique aspects of microbubbles are that they give off a nonlinear response and they expand to a greater degree thanthey can be compressed.Figure 2 shows the dif-ference between a bubble with a linear responseand one with a nonlinear response.The nonlinear microbubble’s echo returns not only the funda-mental frequency but also harmonic frequencies atmultiples of the fundamental frequency.Each suc-cessive harmonic is at a lower amplitude (weaker signal) than the previous one.The strongest is attwice the transmit frequency and is the secondharmonic.New wide-bandwidth transducers arecapable of transmitting at a fundamental frequency and receiving at the second harmonic.A more  Table 2 Properties of an ideal contrast agent • Nontoxic; easily eliminated• Administered intravenously • Passes easily through microcirculation• Physically stable• Acoustically responsive:• Stable harmonics• Capable of rapid disruption  Table 1 Bubble size  TypeSize (microns) Microbubble<100Red blood cell6-8Saline solution16* Albunex3-5 † New contrast agents2.5 ‡ *Approximate size. † 1995 Food and Drug Administration data. ‡  Average size. Figure 1 Microbubbles contain either air or a gas of highmolecular weight. Several of the major differences betweenthe two types of gases are listed here. (Illustration courtesy of DuPont Pharmaceuticals Company.) 1   Journal of the American Society of Echocardiography  Volume 13 Number 10 McCulloch et al 961sophisticated ultrasonic signal processing of thereturning ultrasound signal can filter out the fun-damental frequency and process primarily the sec-ond harmonic frequency.The resulting “harmonicimaging”improves the signal-to-noise ratio,opti-mizing visualization of the contrast population. RESPONSE OF BUBBLES TO ULTRASOUND Figure 3 shows the response of these microbubbles within an ultrasonic (acoustic) field.At low power output (PO) settings,there is mostly a linear response(fundamental enhancement) with some generation of harmonic frequencies.As the PO is increased,thebubbles generate more nonlinear resonance and thusgenerate greater harmonic frequencies.At a high power setting,fracture and destruction of themicrobubble occur,allowing the air or gas inside tobe released.Destruction of the microbubblesdepends on the output power,the frequency of ultra-sound,and the duration of imaging.More bubbledestruction occurs with a lower transducer frequen-cy,higher output power,and longer duration imaging. Figure 2 Nonlinear microbubbles return not only the fundamental (transmitted frequency) but also asecond harmonic frequency that is at twice the transmitted frequency. (Illustration courtesy of DuPontPharmaceuticals Company.) 2,3 Figure 3  As acoustic power is increased, microbubbles move from a linear response to a nonlinear, har-monics-producing response. At maximum power, destruction of the microbubbles occurs. (Illustrationcourtesy of DuPont Pharmaceuticals Company.) 2  MECHANICAL INDEX   An understanding of the mechanical index (MI)(acoustic PO of the ultrasonographic system) andhow it affects microbubbles is critical in optimiz-ing echocardiographic contrast images.The MI is aunit-less number that serves as an indicator of thenonthermal bioeffects.It is a measurement of neg-ative acoustic pressure within the ultrasound fieldand is calculated at the depth where energy con-centration is highest.An important point is thatenergy concentration is not even throughout theultrasound beam.There is less energy at the sidesof the beam and more energy in the center third of the sector and at the transmit focal depths.For thesonographer and echocardiographer,it is easier toequate the MI to acoustic PO or transmit power.The higher the output,the higher the MI number.During standard 2-dimensional imaging,a high MIis necessary for proper penetration and border detection.However,when using contrast agents,alow MI is beneficial to decrease bubble destruc-tion.Several controls and features on the ultra-sonographic system affect the MI,such as trans-ducer frequency,depth,focal zone,and sector size.Ultrasonographic systems now display the MI num-ber on the screen during imaging in 2-dimensionalmode,but changing any of the above mentionedcontrols also changes the displayed MI and thelocation at which it occurs in the image.  Journal of the American Society of Echocardiography  962 McCulloch et al October 2000 Since microbubbles are destroyed by ultrasound,onetechnique for increasing their persistence (the contrasteffect) is to lower the MI (acoustic output power) man-ually on the ultrasonographic system.This will reducethe amount of bubble destruction,thereby prolongingthe duration of the contrast effect.Figure 4 shows anapical 4-chamber view with left ventricular opacifica-tion with contrast.The MI is set at 0.5 (upper left cor-ner) so that there is minimal destruction and an evendistribution of contrast throughout the left ventricle. CONTRAST ARTIFACTS  Attenuation,a commonly seen artifact,is caused by the high echogenicity of microbubbles.When a high concentration of microbubbles exists,a larger por-tion of the ultrasound energy is backscattered andunable to transmit through to the far field structures. Attenuation is seen as shadowing or darker areas inthe mid to far field.Figure 5 is an example of an api-cal 4-chamber view with too high a concentration of microbubbles in the left ventricle.The basal portionsof the left ventricle and left atrial chambers are com-pletely black.This attenuation resolves over time asthe contrast agent is diluted by blood.Significantattenuation is typically noted after a rapid flush andmay be prevented by a slow contrast bolus or by using a diluted infusion method of administration. Figure 4  An apical 4-chamber view demonstrating optimal left ventricular opacification withmicrobubbles. The mechanical index (upper left corner) is set at 0.5. (Image courtesy of the DukeUniversity Echo Lab.)   Journal of the American Society of Echocardiography  Volume 13 Number 10 McCulloch et al 963Swirling is caused by bubble destruction that usual-ly occurs in the near field of the image where the ultra-sound energy is greatest (Figure 6).In such cases,thereis an inadequate concentration of microbubbles (dark-er area),and it is sometimes seen in real-time imagingas contrast swirling.This near-field swirling is usually caused by a combination of factors,which may includetoo high an MI,frame rate,or line density;too little con-trast agent injected;or extremely low flow at the apex(in the case of severe left ventricular dysfunction or alarge apical aneurysm).Sometimes changing the focalzone can alter these factors,especially line density andtransmit beam overlap,which on some machines canbe decreased by moving the focus toward the apex.Other artifacts include a blooming artifact seen onspectral Doppler caused by a returning Doppler signal Figure 5  Apical 4-chamber view of the left ventricle showing attenuation in the far field because the con-centration of microbubbles is too high. (Image courtesy of the University of Chicago Echo Lab.) Figure 6  Apical 4-chamber view showing swirling in the apex caused by bubble destruction. Swirling isthe result of a combination of factors (see text). (Image courtesy of the Duke University Echo Lab.)
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