Mark J Monaghan. Imaging techniques ROLE OF REAL TIME 3D ECHOCARDIOGRAPHY IN EVALUATING THE LEFT VENTRICLE TIME 3D ECHO TECHNOLOGY

Transcription

1 Take the online multiple hoie questions assoiated with this artile (see page 130) Correspondene to: Dr Mark J Monaghan, Department of Cardiology, King s College Hospital, Denmark Hill, London SE5 9RS, UK; mark.monaghan@ kingsh.nhs.uk Imaging tehniques ROLE OF REAL TIME 3D ECHOCARDIOGRAPHY IN EVALUATING THE LEFT VENTRICLE REAL E Mark J Monaghan Heart 2006; 92: doi: /hrt valuation of left ventriular (LV) size and funtion are by far the most ommon reasons for performing ehoardiography in the adult patient. Important diagnosti, prognosti, and treatment deisions rest upon LV morphology analysis; the widespread bedside availability, ost, and non-invasive nature of ehoardiography has meant that this tehnique has beome the method of hoie in most situations for performing this analysis. However, both M mode and two dimensional (2D) ehoardiography make important geometri assumptions about the LV whih leads to inauraies in measurements. There is also poor inter- and intra-observer variability whih limits the use of the tehnique in follow up of patients and also in sientifi studies. Many ehoardiographi departments perform eyeball analysis of global and regional LV funtion and provide visual estimates of ejetion fration beause existing quantifiation methods (from M mode and 2D Eho) are both time onsuming and diffiult to perform. In an era when so many important and often ostly deisions are made upon these data it is inumbent upon departments that aurate and reproduible eho quantifiation methods are utilised espeially sine the gold standard tehnique of ardia magneti resonane (CMR) is not so widely available, is more ostly, annot be used on those with implanted paemakers or defibrillators, and is disliked by many patients. Three dimensional (3D) ehoardiography has been available for several years using time onsuming and diffiult reonstrution tehniques (often utilising transoesophageal studies). However, reent advanes in omputer proessing and transduer onstrution tehniques have meant that real time transthorai 3D ehoardiography is now available from major ultrasound system manufaturers. Software programs to analyse 3D datasets of the LV are also now readily available; this ombination of new instrumentation and software has been shown to provide highly aurate (ompared to CMR) analysis of LV morphology and funtion, suh that this methodology is likely to ensure that ehoardiography remains the first hoie tehnique for noninvasive evaluation of the LV. TIME 3D ECHO TECHNOLOGY As previously mentioned, early 3D ehoardiographi tehniques relied upon the aquisition of multiple ross setional (2D) images using freehand transthorai or transoesophageal imaging. The spatial and temporal relationships of eah image had to be registered and gating to the ardia and respiratory yle also performed before a time onsuming reonstrution of a 3D dataset ould be undertaken. ECG and respiratory yle gating an largely be avoided by aquiring the 3D datasets in real time and this is ahieved by using a matrix array probe. This type of probe ontains omplex eletronis and individual elements whih permits multidiretional beam steering and allows a 3D dataset of approximately to be aquired. This failitates 3D visualisation of valve strutures or part of the LV in real time. In order to apture a dataset large enough to over the whole of the LV, the transduer is positioned over the apex and several (usually four) smaller real time datasets are aquired during briefly held respiration and eletronially stithed together over four or five sequential ardia yles. In this way a pyramidal 3D dataset of is obtained at a frame rate of Hz. This is usually large enough and also fast enough to allow omprehensive analysis of the LV. However, in order for this analysis to be performed, the 3D dataset needs to be rendered within the ultrasound system. Volume rendering is a proess whereby the intraardia strutures are reonstruted within the omputer memory so that the dataset an be setioned eletronially in any plane, allowing visualisation of any struture within the heart from any viewpoint. Viewing a volume rendered 3D dataset of the heart is analogous to standing outside a house and being unable to see in without taking some or part of the walls away. By setioning or ropping away part of the dataset it is possible to see inside the heart and view the anatomial orientation and motion of intraardia strutures, inluding the LV myoardium. An example of a 3D eho image 131 Heart: first published as /hrt on 19 Deember Downloaded from on 3 Otober 2018 by guest. Proteted by opyright.

2 132 Figure 1 Full volume 3D eho image of the left ventrile (LV) in a four hamber equivalent view. The anterior wall of the LV has been ropped (setioned) away to reveal a large apial aneurysm ontaining thrombus. The size, shape, and morphology of the thrombus an be appreiated. In the moving real time images its mobility and overall LV funtion an be appreiated. of the LV is shown in fig 1. In this ase the anterior wall of the ventrile has been ropped away to allow visualisation of the LV morphology, revealing a large apial aneurysm ontaining thrombus. The starting point for any analysis of LV morphology or funtion is to use the 3D dataset to alulate volumes of the ventrile and/or myoardium at multiple points during the ardia yle. Several online or offline software pakages are available to do this. They usually work by setioning the voxel based dataset of the LV into several separate 2D planes and a semi-automated endoardial border detetion proess is performed on eah plane. Anatomial landmarks suh as Figure 2 A mathematial model or ast of the LV whih is obtained using semi-automated endoardial border traking from the 3D dataset. Following identifiation of a few anatomial landmarks the ast is automatially segmented into the standard 16 or 17 segments. The volume of eah segment (relative to the LV entre of gravity) or the volume of the whole avity an be alulated for eah frame in the ardia yle (see fig 3). the mitral annulus and apex are identified by the user and the software reates a mathematial model or ast of the LV whih allows time volume alulations to be performed for the entire ardia yle (fig 2). The dataset aquisition takes approximately 4 5 seonds and, providing no orretion to the deteted endoardial boundaries needs to be performed, the analysis to this stage an be performed in under a minute. Three dimensional ehoardiography an suffer with poor image quality in the same way that 2D eho an. Fortunately, ultrasound ontrast agents an also be used with 3D eho when image quality is suboptimal and this means that analysable 3D datasets an be obtained in virtually all patients. MEASUREMENT OF LV VOLUME AND EJECTION FRACTION M Mode alulations of LV volumes assume that the LV is a prolate ellipse and that by measuring a single minor axis dimension and ubing it, volume an be alulated. Despite the fat that there are numerous flaws in this assumption and that errors in measurement beome very large when ubed, it is surprising how often this alulation is still utilised in linial pratie. Furthermore, it is still widely available in eho reporting and analysis software. Two dimensional eho alulation of LV volumes using the method of diss (Simpson s rule) makes signifiantly less geometri assumptions, espeially when utilised in a biplane format. However, there is still the assumption that the ventrile an be represented by a series of staked diss with varying diameters. In patients with regional wall motion abnormalities or LV aneurysms, et, this assumption may fail. Three dimensional ehoardiography makes no assumptions about the shape of the LV it alulates it as it is. In addition, the endoardial position is measured at many hundreds of points over the LV surfae, therefore the alulation of volume is more aurate and reproduible than when only one or two 2D eho planes are used. There are now many published studies whih have shown high onordane between 3D eho alulations of LV volume and ejetion fration ompared to the gold standard of CMR. 1 5 Most of these studies have also shown signifiant inreases in auray and reproduibility over onventional 2D ehoardiography methods. Figure 2 shows an example of a mathematially derived model or ast of the LV. In real time the ast moves to simulate LV ontration and relaxation. It an be rotated on the omputer sreen using a mouse so that regional funtion an be visually appreiated. In addition, the 16 or 17 Amerian Soiety of Ehoardiography defined segments are identified on the ast. The volume of the ast (LV) is alulated for every frame in the 3D dataset and plotted as a graph of volume against time, as shown. End diastoli volume, end systoli volume, and ejetion fration are automatially derived from this graph and displayed, as shown in fig 3. LV SHAPE It is well known that the shape of the LV is an additional useful parameter to assess in patients with LV dysfuntion. As funtion deteriorates and LV size inreases, the ventrile assumes a more globular rather than elliptial shape. Two dimensional ehoardiography has previously been used to derive a 2D spheriity index whih relates to the ratio of the Heart: first published as /hrt on 19 Deember Downloaded from on 3 Otober 2018 by guest. Proteted by opyright.

3 ross setional area of the LV (from an apial four hamber view) to a irle with a diameter equivalent to LV major end diastoli long axis. As the ventrile beomes more irular, the ratio approahes unity. Clearly a spheriity index whih is derived from 3D LV volumes rather than 2D area will reflet ventriular shape more aurately. A 3D derived spheriity index has been desribed 6 and is alulated by dividing the LV end diastoli volume (alulated from a 3D dataset) by the volume of a sphere, the diameter of whih is the LV major end diastoli long axis. This spheriity index has been shown to be an earlier and more aurate preditor of remodelling in patients following aute myoardial infartion than other linial, eletroardiographi, or ehoardiographi variables. 6 Offline 3D analysis software now permits rapid alulation of a 3D Figure 3 Three dimensional apial full volume dataset whih has been segmented into 2D four hamber, two hamber, and short axis slies. Semiautomated endoardial traking (yellow line) an be seen, heked, and edited using these views. From this a mathematial model or ast of the LV is reated using all 3D data points. At the bottom, alulated LV volume (from the ast) is plotted against time during one ardia yle. End diastoli and end systoli volumes plus ejetion fration and spheriity index are derived from these data. spheriity index using 3D LV volume data, derived as previously desribed. LV MASS Calulation of LV mass from either M mode or 2D ehoardiography makes the same inherent assumptions and suffers from the same inauraies as previously desribed for volume alulations. 7 8 It is surprising that, given the poor reproduibility of these onventional eho methods for LV mass alulations, they are still widely used in both routine linial and researh follow up of patients undergoing antihypertensive treatment, where regression of mass is being studied. Using the same full volume 3D dataset of the LV and user interation it is possible to identify epiardial boundaries of Figure 4 Example of LV mass alulation where apial four and two hamber setions have been reated from a full volume dataset of the LV. In a semi-automated proess the endoardial and epiardial/right ventriular septal borders of the LV myoardium is identified and a biplane Simpson s rule alulation applied to derive both LV and myoardial volumes. The latter is multiplied by the speifi gravity of heart musle to obtain the displayed mass of 159 g. 133 Heart: first published as /hrt on 19 Deember Downloaded from on 3 Otober 2018 by guest. Proteted by opyright.

4 134 the LV myoardium. This is used by analysis software to alulate an epiardial ast of the ventrile. The volume of this ast an be subtrated from an endoardial ast (reated from the same dataset) to give the volume of the LV myoardium. By multiplying this by the speifi gravity of myoardium, LV mass is derived. This has been demonstrated to be a rapid and highly aurate alulation when ompared to CMR. 9 Furthermore it has been shown to have signifiantly better agreement with CMR than 2D eho methods. An example of LV mass alulation from a 3D dataset is shown in fig 4. The poor reproduibility of onventional ehoardiographi methods for alulation of LV mass has led some to speulate that, despite inreased proedural ost, CMR requires signifiantly less patients in LV hypertrophy regression studies and therefore the overall ost of using CMR is lower than ehoardiography. However, now that 3D eho tehniques have been shown to have high auray and reproduibility (ompared to CMR) it is likely that this method will be the tehnique of hoie in the future for these types of studies. REGIONAL LV FUNCTION AND DYSSYNCHRONY ANALYSIS While aurate non-invasive alulation of global LV funtion is important, in the ontext of patients with heart failure and potential LV dyssynhrony, analysis of regional funtion in the time domain is of more importane. Several ehoardiographi tehniques inluding tissue Doppler have been shown to detet intraventriular dyssynhrony, and these methods have been used in the seletion of patients for ardia resynhronisation therapy (CRT). Real time 3D ehoardiography is showing onsiderable promise in this diretion as an aurate and reproduible tool for deteting and quantifying LV intraventriular dyssynhrony. It also appears to be helpful in prediting patients who will respond to CRT and those that will ahieve reverse remodelling following treatment. 10 In order to do this, an LV ast is derived from a full volume 3D dataset, as previously desribed. Some anatomial landmarks are identified on the ast and then it is automatially divided into the standard 16 or 17 segments desribed by the Amerian Soiety of Ehoardiography. The entre of gravity of eah ast an also be alulated and the volume of eah segment relative to the entre of gravity measured. Eah of these segmental volumes has a pyramidal shape and the volume of eah pyramid is alulated and plotted for eah ast/dataset throughout the ardia yle. In this way we ahieve a series of plots representing the hange in volume for eah segment throughout the yle, as shown in fig 5. In a ventrile with synhronous ontration of all segments, we would expet eah segment to ahieve its minimum volume at almost the same point in the ardia yle, whereas in a dyssynhronous ventrile there will be a dispersion in the timing of the point of minimum volume for eah of the 16 or 17 segments. The degree of dispersion an be alulated by measuring the standard deviation of the time to ahieve minimum volume and then orreting that for the R-R interval. This allows derivation of a systoli dyssynhrony index whih an be used to quantify the degree of LV dyssynhrony from a omparison of all segments, whereas B mode imaging tehniques suh as tissue Doppler only allow simultaneous omparison of segments within the san plane. We have shown that there is modest orrelation Figure 5 LV regional volume urves plotted for one ardia yle are seen at the top in a patient with a biventriular paemaker turned into sense mode. At the bottom the same regional volume urves are seen one paing has been ativated. With paing turned off it an be seen that eah of the LV regions or segments ahieve their minimum volume at a different point in the ardia yle, indiating signifiant intraventriular dyssynhrony. However, when biventriular paing is ativated, the regional urves are muh more aligned indiating more synhronous ontration of all segments. Heart: first published as /hrt on 19 Deember Downloaded from on 3 Otober 2018 by guest. Proteted by opyright.

5 Figure 6 Parametri LV ast (top) and bulls eye display (bottom) in a patient pre- (left) and post- (right) ardia resynhronisation therapy (CRT). Time to minimum volume is signifiantly delayed in the septal segment urves and on the parametri image (red olour) pre-crt. Following CRT with right ventriular paing first, most segments ahieve minimum volume at the same time in the ardia yle and the parametri image displays a more homogeneous blue olour. between some tissue Doppler measures of LV dyssynhrony and the 3D systoli dyssynhrony index in patients with both good and poor LV funtion. Tissue Doppler methods are urrently onsidered the gold standard for evaluating dyssynhrony and it remains to be determined if 3D based methods are superior. Intuitively, one would expet that CRT is likely to be of more benefit in patients with evidene of dyssynhrony, whereas patients with a low dyssynhrony index and therefore relatively synhronous LV ontration may not ahieve muh benefit from CRT. Table 1 Three dimensional ehoardiography for left ventriular (LV) dyssynhrony analysis Allows omparison of timing of all LV segments Regional volumes provide omposite of all vetors of motion Exellent spatial resolution Quik aquisition and analysis Systoli dyssynhrony index is simple, intuitive, reproduible, and preditive of ardia resynhronisation therapy suess Graphial parametri display of dyssynhronous segments guide to LV lead plaement The systoli dyssynhrony index in patients with heart failure appears to be independent of the aetiology of the LV dysfuntion; it demonstrates an inverse logarithmi orrelation with the ejetion fration so that, in general, patients with a higher dyssynhrony index have a lower ejetion fration. This is not surprising. However, of more interest is the fat that the relation between the dyssynhrony index and ejetion fration is preserved, irrespetive of QRS duration. This means that there is an important ohort of heart failure patients with low ejetion fration, narrow QRS, and 3D eho evidene of dyssynhrony. These may represent a potentially new patient population for CRT who are urrently denied this treatment beause they have normal QRS duration. Other ehoardiographi tehniques to evaluate LV dyssynhrony have also identified the fat that mehanial dyssynhrony an our in patients with normal QRS. It remains to be seen whih ehoardiographi tehnique will be more effetive in identifying these potential new CRT responders. At the other end of the spetrum we an identify a group of patients who fit urrent riteria for CRT in that they have low ejetion fration and broad QRS; however, these patients do not have muh evidene of LV dyssynhrony and their systoli dyssynhrony index is low. This group of patients may represent the 20 30% of subjets who do not respond to CRT. Figure 7 Stages of 3D image aquisition and LV analysis. 135 Heart: first published as /hrt on 19 Deember Downloaded from on 3 Otober 2018 by guest. Proteted by opyright.

6 136 3D ehoardiography for evaluating the left ventrile: key points Left ventriular (LV) morphology and funtion most ommon ehoardiography request M mode and 2D ehoardiography make inorret geometri assumptions about the LV Inaurate and poor reproduibility of M mode/2d analysis 3D ehoardiography makes no geometri assumptions 3D sees the LV as it is 3D measures endoardial position at.700 points 3D ehoardiography has exellent orrelation with ardia magneti resonane (CMR) for volume, mass, and ejetion fration 3D reproduibility omparable with CMR Using urrent offline software it an take approximately five minutes for an experiened operator to perform a dyssynhrony analysis. This makes the tehnique very suitable for identifying suitable patients pre-crt and evaluating the results of the proedure. However a five minute analysis time is too long for pratial use during an optimisation proedure, where repeated measurements are required following paemaker adjustments. Future modifiations of the analysis software will failitate rapid online alulation of the dyssynhrony index whih an be measured following eah paemaker parameter hange. Obviously the aim of optimisation in this way would be to ahieve the lowest possible dyssynhrony index to minimise intraventriular dyssynhrony. Parametri bulls eye displays of the timing of LV ontration are also available. This methodology examines regional LV ontration at approximately points over the endoardial surfae (from the 3D dataset) rather than in just 16 or 17 segments. Colour oding is used to identify whih regions are ontrating last and this ould potentially be used by eletrophysiologists to selet the optimal position for the LV eletrode. Examples of parametri 3D images preand post-crt are shown in fig 6. Parametri images an be fused with an angiographi display of the oronary sinus anatomy to assist in this proess. The use of real time 3D eho for the evaluation of patients being onsidered for CRT is still in its infany. However, early data suggest that this is a powerful tool for deteting, quantifying, and displaying LV dyssynhrony. Three dimensional LV dyssynhrony analysis may help to selet patients who will or will not benefit from CRT, inluding those with narrow QRS (table 1). It has the potential to be used to guide paing eletrode positioning in the eletrophysiology laboratory and it ould be used to guide optimisation of paemaker parameters. However, perhaps the most endearing feature of this tehnique in this ontext is that it is intuitive and provides a graphi display whih is appealing to eletrophysiologists and other ardiologists who refer patients for CRT evaluation. As previously desribed and illustrated in fig 7, the aquisition of a full volume dataset from a 3D san takes a few seonds and may be performed at the bedside. Subsequent reation of a mathematial model of the LV allows standard parameters of global funtion and morphology to be alulated. In addition, more sophistiated measures of regional funtion and LV synhroniity may also be derived from the same dataset. CONCLUSION Advanes in ehoardiographi instrument tehnology and omputer proessing power have brought 3D ehoardiography from being a time onsuming researh tool to being a powerful linially appliable tehnique that an provide answers to the most ommonly asked question from any ardia imaging methodology what is the LV funtion? Three dimensional ehoardiographi imaging will soon beome a standard imaging modality on all new eho systems. In the future, it will seem as unaeptable to perform an ehoardiographi study without using 3D to analyse global and regional LV funtion as it is to perform a onventional 2D eho study without use of Doppler. REFERENCES 1 Jenkins C, Briknell K, Hanekom L, et al. Reproduibility and auray of ehoardiographi measurements of left ventriular parameters using realtime three-dimensional ehoardiography. J Am Coll Cardiol 2004;44: An important paper demonstrating good reproduibility and auray of 3D versus CMR in assessing LV volumes. 2 Zeidan Z, Erbel R, Barkhausen J, et al. Analysis of global systoli and diastoli left ventriular performane using volume-time urves by real-time threedimensional ehoardiography. J Am So Ehoardiogr 2003;16: Kühl HP, Shrekenberg M, Rulands D, et al. High-resolution transthorai real-time three-dimensional ehoardiography: quantitation of ardia volumes and funtion using semi-automati border detetion and omparison with ardia magneti resonane imaging. J Am Coll Cardiol 2004;43: Bu L, Munns S, Zhang H, et al. Rapid full volume data aquisition by real-time 3-dimensional ehoardiography for assessment of left ventriular indexes in hildren: a validation study ompared with magneti resonane imaging. JAm So Ehoard 2005;18: Gutierrez-Chio JL, Zamorano JL, Perez de Isla L, et al. Comparison of left ventriular volumes and ejetion frations measured by three-dimensional ehoardiography versus by two-dimensional ehoardiography and ardia magneti resonane in patients with various ardiomyopathies. Am J Cardiol 2005;95: Mannearts HFJ, Van Der Heide JA, Kamp O, et al. Early identifiation of left ventriular remodelling after myoardial infartion, assessed by transthorai 3D ehoardiography. Eur Heart J 2004;28:680. This is the first paper to desribe the implementation of LV shape analysis using a 3D spheriity index, and it is a key referene. 7 Gottdiener JS, Livengood SV, Meyer PS, et al. Should ehoardiography be used to assess effets of antihypertensive therapy? Test-retest reliability of ehoardiography for measurement of left ventriular mass and funtion. JAm Coll Cardiol 1995;25: This paper identifies why we need to do better than urrent methods for ehoardiographi evaluation of LV mass. 8 Myerson SG, Montgomery HE, World MJ, et al. Left ventriular mass: reliability of M-mode and 2-dimensional ehoardiographi formulas. Hypertension 2002;40: Mor-Avi V, Sugeng L, Weinart L, et al. Fast measurement of left ventriular mass with real-time three-dimensional ehoardiography: omparison with magneti resonane imaging. Cirulation 2004;110: Demonstrates that the reproduibility and auray of 3D mass measurements is signifiantly better than those obtained from 2D. 10 Kapetenakis S, Kearney MT, Siva A, et al. Real-time three-dimensional ehoardiography. A novel tehnique to quantify global left ventriular mehanial dyssynhrony. Cirulation 2005;112: Although from our own unit, this is atually the first published paper to desribe and validate a dyssynhrony index that an be used for patient seletion for CRT. Heart: first published as /hrt on 19 Deember Downloaded from on 3 Otober 2018 by guest. Proteted by opyright.