Physiological Measurement
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Quantitative description of the 3D regional mechanics of the left atrium using cardiac magnetic resonance imaging To cite this article: P Kuklik et al 2014 Physiol. Meas. 35 763
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Institute of Physics and Engineering in Medicine Physiol. Meas. 35 (2014) 763–775
Physiological Measurement
doi:10.1088/0967-3334/35/5/763
Quantitative description of the 3D regional mechanics of the left atrium using cardiac magnetic resonance imaging P Kuklik 1 , P Molaee 1 , P Podziemski 2 , A N Ganesan 1 , A G Brooks 1 , S G Worthley 1 and P Sanders 1 1
Centre for Heart Rhythm Disorders (CHRD), South Australian Health and Medical Research Institute (SAHMRI), University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia 2 Faculty of Physics, Warsaw University of Technology, Warsaw, Poland E-mail: [email protected] Received 19 August 2013, revised 25 February 2014 Accepted for publication 28 February 2014 Published 26 March 2014 Abstract
The left atrium (LA) plays an important role in the maintenance of hemodynamic and electrical stability of the heart. One of the conditions altering the atrial mechanical function is atrial fibrillation (AF), leading to an increased thromboembolic risk due to impaired mechanical function. Preserving the regions of the LA that contribute the greatest to atrial mechanical function during curative strategies for AF is important. The purpose of this study is to introduce a novel method of regional assessment of mechanical function of the LA. We used cardiac MRI to reconstruct the 3D geometry of the LA in nine control and nine patients with paroxysmal atrial fibrillation (PAF). Regional mechanical function of the LA in pre-defined segments of the atrium was calculated using regional ejection fraction and wall velocity. We found significantly greater mechanical function in anterior, septal and lateral segments as opposed to roof and posterior segments, as well as a significant decrease of mechanical function in the PAF group. We suggest that in order to minimize the impact of the AF treatment on global atrial mechanical function, damage related to therapeutic intervention, such as catheter ablation, in those areas should be minimized. Keywords: atrial mechanical function, atrial fibrillation, AF ablation, 3D reconstruction, cardiac MRI S Online supplementary data available from stacks.iop.org/PM/35/763/mmedia
(Some figures may appear in colour only in the online journal) 0967-3334/14/050763+13$33.00
© 2014 Institute of Physics and Engineering in Medicine Printed in the UK
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1. Introduction The mechanical function of the left atrium (LA) plays an important role in hemodynamic function of the heart. Impaired LA mechanical function results in an increased risk of thromboembolic events due to impaired flow in the LA appendage (Al-Saady et al 1999). One of the most prevalent causes of impaired LA function is atrial fibrillation (AF)—a complex disturbance of the conduction of the electrochemical waves in the atria resulting in a lack of coordinated global mechanical function (Zipes and Jalife 2004). Since termination of AF was shown to improve atrial mechanical function (Sanders et al 2003), the restoration of sinus rhythm has become an important clinical target. One of the ways of restoring sinus rhythm in AF is an ablation procedure, during which a set of catheters is introduced into the atria and areas responsible for maintenance of the arrhythmia are targeted and destroyed. In the case of chronic AF, the amount of ablation required to terminate arrhythmia is significant, contributing to the deterioration of LA function (Wylie et al 2008). In order to minimize the detrimental impact of ablation on global LA function, the damage should be minimized in areas crucial for mechanical function. In this study, we aimed to characterize a novel method to quantify the regional mechanical function of the LA, and in order to identify the regions contributing the greatest mechanical function. Current methods of cardiac mechanical function assessment are based on imaging methods such as computed tomography (Nakazato et al 2011), magnetic resonance imaging (MRI) (Bergvall et al 2006, Moore et al 2000), magnetic resonance velocitometry (Wong et al 2009), positron emission tomography (Shen et al 1999, Slart et al 2004), echocardiography (Thomas 2007, Corsi et al 2005) and catheterization (Gepstein et al 1997). Regional function of the atria has been assessed using several approaches (Stefanadis et al 2001) including: pulsed wave and colour Doppler tissue imaging (Thomas et al 2003), two-dimensional speckle-tracking echocardiography (Appleton et al 2009, Sun et al 2013, Henein et al 2012), velocity vector imaging (Kojima et al 2012), strain Doppler imaging (Matsumoto et al 2006), cardiac MRI (Nori et al 2009, Muellerleile et al 2012) and three-dimensional (3D) electrophysiological mapping systems (Kuklik et al 2010, Chen et al 2012). Ultrasound-based methods characterize regional function through analysis of the motion of a fixed point in a given region, thus not providing the true average function of the whole region. 3D electrophysiological mapping system approaches characterize the motion of whole regions; however, these require the introduction of catheters, which may not be feasible in practice. Colour Doppler tissue imaging and speckle-tracking (e.g. Thomas et al 2003), despite obvious advantages (low cost and noninvasive in nature), have significant limitations, including angle-dependence of tissue and issues with poor reproducibility between investigators. In this study, we aim to strengthen the above methods of regional function assessment using cardiac MRI imaging of the LA to reconstruct the 3D geometry of the chamber and quantify regional motion of the atrial walls using the concept of regional ejection fraction and regional wall velocity.
2. Methods 2.1. Patient characteristics
MRI cine images of nine patients with paroxysmal atrial fibrillation (PAF) were analysed with a reference group of nine patients with structurally normal hearts undergoing radiofrequency ablation for atrioventricular re-entry tachycardia with left-sided accessory pathways and no history of AF. Six males and three females were in each group with the mean age for the 764
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control group 58 ± 6 and 67 ± 7 for the PAF group. All patients provided written informed consent for their procedures. 2.2. MRI imaging protocol
All patients underwent cardiac MRI at 1.5 T (Siemens Avanto, Siemens Medical Solutions, Erlangen, Germany) during sinus rhythm. Sequential steady-state free-precession short-axis cine sequences were acquired with 1.2 mm in-plane resolution, 6 mm slice thickness and no interslice gaps through the atrium in short axis (SA) and four chamber view (4C) orientations. Slices were taken from the most cranial aspect of the LA and sequentially to the cardiac apex at end-expiration. 2.3. Image segmentation
Segmentation of the atrium from MRI images was performed using a region growing algorithmbased on pixel intensity. The algorithm starts from an initial seed pointed by the operator and grows until the segmented part of the image is surrounded by pixels of intensity lower by one standard deviation of intensity from the average intensity of pixels within the currently segmented region. Segmentation was manually supervised and corrected in case of an overflow to neighbouring structures (e.g. due to lack of a clearly defined boundary between the LA and right atrium) or scanning artefacts. Segmentation was performed for all images in SA and 4C orientations and at each point of the cycle (25 time points in cycle) taking around 30 min per patient. 2.4. Construction of a 3D grid
Due to the geometrical non-uniformity of the initial dataset (in-plane image resolution was 1.2 mm with a 6 mm gap between images), we transformed it into a uniform grid which was later used as a starting point for surface reconstruction. After assessing the effect of a voxel size on obtained chamber volume (see figure 1 in the supplementary materials, available from stacks.iop.org/PMEA/35/763/mmedia), due to the lack of a clear plateau, we selected a value of 2 mm. Intensities of the 3D grid elements Igrid(i, j,k) were obtained by interpolation of the intensities of the MRI image pixels: I grid (i, j, k) = (1 − λ)I MRI (i , j , k ) + λI MRI (i , j , k )
(1)
where I denotes intensity, (i , j , k ) are coordinates of the closest pixel in a stack of MRI images where k denotes an image index in a stack. k is the index of the second closest image. λ is a coefficient calculated using distances to the two closest MRI images in a stack: dist({i, j, k}, {i , j , k }) (2) λ= dist({i , j , k }, {i , j , k }) where dist({i, j, k}, {i , j , k }) is the Euclidean distance between elements {i, j, k} and {i , j , k } in 3D space. In other words, cine images were upsampled to a spatially uniform volumetric grid, using linear interpolation. 2.5. Surface reconstruction
The endocardial surface was reconstructed based on the 3D volume model using the marching cubes algorithm (Lorensen and Cline 1987) resulting in a triangularized endocardial surface of the atrium. Surface smoothing was performed by averaging the spatial coordinates of each surface node. An example of the reconstruction is shown in figure 1. 765
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(a)
(b)
(c)
(d)
Figure 1. Example reconstruction of the geometry of the LA. Stack of MRI images with segmented areas of LA in black stripes (a). Volume model of the LA (b). Reconstructed surface (c). Surface after applying the smoothing algorithm (d).
2.6. Atrium segmentation
The LA surface was manually segmented into six distinct segments: anterior, lateral, roof, septal, posterior and inferior segment (Ho et al 1999) (see figure 2). Anterior, lateral, septal and posterior segments were reconstructed using the SA projection and the function of the roof segment was assessed using the 4C projection. Segmentation of the chamber was performed manually at the first point of the cardiac cycle and then regions were propagated to the remaining phases of the cycle according to the following equation: Segment Tin = Segment min(d Tin , Tjn−1 j
(3)
where Segment(T) is a function returning a segment identifier for a given triangle Ti of the surface in phase n (n is a number between 0 and 24 corresponding to the cardiac phase). Function d is a Euclidean distance between the geometrical centres of two triangles. In simpler words, to find a segment identifier for a given triangle, the closest triangle in the preceding phase is located and its segment identifier copied. 766
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(a)
(b)
(c)
Figure 2. Example of the LA segmentation. For each cardiac phase, the LA was segmented into six distinct segments. Segments obtained from the short axis projection (a). Roof segment obtained from the four chamber projection (b). The segmental volume taken by each segment is then calculated for each cardiac phase resulting in a plot depicting segmental volume throughout the whole cycle (c).
2.7. Metrics used to quantify the mechanical function of the atrial wall
Since MRI cine images provide the position of the atrial wall throughout the cardiac cycle, metrics quantifying mechanical function have to be based on this information. The position of the atrial wall in space throughout the cardiac cycle enables the construction of two general types of metrics: (i) a metric based on a velocity of the atrial wall and (ii) a metric-based on a volume of space occupied by a given region of the surface throughout the cycle. Those two metrics may result in different estimates since volumetric change depends on the geometrical shape of the surface (two surfaces moving with the same velocity may result in a different occupied volume depending on their shape). In order to assess the regional mechanical function of the LA, we used the concept of a regional ejection fraction (REF) parameter as defined in Kuklik et al (2010). REF is defined using a segmental volume assessing the relative contribution of a given region of the chamber towards the global volume of the chamber. Segmental volume is defined as a cone with a vertex located in the geometrical centre of the reconstructed chamber (calculated at each phase of the cycle to account for translational motion of the chamber) and a base defined by a surface of the given region (e.g. anterior LA) (see figure 3). The volume of each cone changes throughout the heart cycle, providing a measure of the contribution
2.7.1. Regional ejection fraction.
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Figure 3. Definition of regional systolic and diastolic volume. C is located at the geometrical centre of the chamber. Ssystolic and Sdiastolic denote a portion of the endocardial surface defined as a given region in systole and diastole, respectively. Regional volume is defined as the volume of a solid defined by a vertex C and surface S.
of a given region towards global volumetric changes of whole chamber at each point of the cycle. For each region of the LA, segmental volume was calculated for all phases of the cycle. Two types of REF parameters were used: REF-TC related to the total contraction and REFAC related to an active component of contraction. REF-TC was defined using the following equation: Vdiastolic − Vsystolic (4) REF − TC = Vdiastolic where Vdiastolic is a segmental volume taken by a given segment in diastole, and Vsystolic is a segmental volume in systole. The second parameter (REF-AC) is related to an active component of a contraction and is defined using segmental volumes at the phase of the cycle related to the greatest volume and 18th phase of the cycle. REF-AC is defined using the following equation: Vdiastolic − V18 (5) Vdiastolic where Vdiastolic is the maximum segmental volume, and V18 the segmental volume during the 18th phase of the cycle. Both parameters reflect regional volumetric changes related to chamber contraction. REF-TC reflects the total volumetric change between systole and diastole. However, volumetric change between systole and diastole includes atrial passive filling and is therefore not specifically related to an active phase of atrial contraction. In order to reflect the volumetric changes related to atrial contraction, REF-AC was devised as a difference between the diastolic and 18th phase of the cycle (the 18th phase was selected as the middle of the plateau in the regional volumetric plot following active atrial contraction, see figure 2). REF − AC =
The motion of the endocardial surface was previously characterized and assessed in several studies (Landini et al 2005, Eusemann et al 2001, 2003). Based on those studies we introduced a second parameter to quantify the mechanical function of a given atrial region: region motion velocity (RMV). In order to calculate RMV, the velocity for each triangle of the surface within a given segment is calculated. The velocity of the triangle is defined as a ratio of the distance between the centre of a given triangle and the chamber surface in the next time point (phase) and time interval. Then, RMV is calculated
2.7.2. Region motion velocity.
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Figure 4. Example distribution of the regional motion velocity (RMV) in the anterior view of the LA. Left map shows the distribution of maximum RMV value. Right map shows the averaged value throughout the cardiac cycle.
as a mean of the velocities of the triangles belonging to a given region. Two parameters are calculated for each region using RMV: maximum-RMV (maximum RMV throughout the cycle) and mean-RMV (mean RMV throughout the cycle). An example of the spatial distribution of the RMV is shown in figure 4. 2.8. Inter-observer variability
Two independent and experienced investigators performed LA segmentation and analysis in order to establish an inter-observer agreement. The agreement was assessed via intra-class correlation coefficients (ICCs) with 95% limits of agreement. Absolute ICCs agreement was calculated via a two way random effects model. 2.9. Statistical analysis
Data are presented as a mean ± standard deviation. All variables were compared using a linear mixed effects model, with fixed effects of anatomical region (n = 6) and group (n = 2) and their interaction. Age and patient id were introduced as random variables. If the interaction term was not significant, the model was run again without the interaction term to examine the main effects. Post hoc tests for segments were conducted with Sidak confidence interval adjustment. Statistical significance was established at p < 0.05. Statistical analyses were performed in SPSS version 19 (IBM Corporation, Armonk, NY). 3. Results LA geometry was reconstructed for each patient in SA and 4C view followed by segmentation and calculation of regional volumetric changes and wall velocities. An example of a time course of regional volumes is shown in figure 2. An example of the motion of the reconstructed surface is shown in the movies in the supplementary materials (available online at stacks.iop.org/PMEA/35/763/mmedia). REF-TC and REF-AC for distinct segments of the LA are shown in figures 5(a) and (b). Both REF parameters were significantly higher in the control group as compared to the PAF group (p < 0.001 for REF-TC and p < 0.005 for REF-AC). Mean REF-TC in the control group was 0.51 ± 0.19 versus 0.4 ± 0.18 in the PAF group. Mean REF-AC in the control group was 0.21 ± 0.15 versus 0.15 ± 0.12 in the PAF group. 769
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(a)
(c)
(b)
(d)
Figure 5. Regional ejection fraction related to total contraction (REF-TC) (a), regional ejection fraction related to an active component of contraction (REF-AC) (b), mean region motion velocity (mean-RMV) (c) and maximum region motion velocity (maxRMV) (d) for distinct segments of the LA for the control group (n = 9) and the paroxysmal atrial fibrillation group (n = 9). Error bars denote ± 1 SD.
Mean-RMV and max-RMV for distinct segments of the LA are shown in figures 5(c) and (d). Both RMV parameters were significantly higher in the control group as compared to the PAF group (p < 0.001 for mean-RMV and p < 0.01 for max-RMV). Mean-RMV in the control group was 0.028 ± 0.009 m s−1 versus 0.023 ± 0.007 m s−1 in the PAF group. Max-RMV in the control group was 0.059 ± 0.028 m s−1 versus 0.048 ± 0.022 m s−1 in the PAF group. A significant regional variation for all parameters (REF-TC, REF-AC, mean-RMV and max-RMV) was observed (p < 0.001). For REF-TC, REF-AC and mean-RMV roof and posterior segments were associated with lower values as compared to anterior, septal and lateral segments (p < 0.01). For max-RMV roof, posterior and lateral segments had lower values as compared to anterior and septal (p < 0.01). The non-significant (p = 0.77 for REF-TC, p = 0.11 for REF-AC, p = 0.69 for mean-RMV and p = 0.94 for max-RMV) group∗ region interaction term demonstrated that the pattern of parameters was the same in the PAF and control groups. In overall, inter-observer reliability of regional analysis was high with ICC > 0.94 and Cronbach’s α > 0.95 (see table 1). The lowest ICC was found for REF-AC metric (ICC = 0.949) and the highest with mean-RMV (ICC = 0.973). 770
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Table 1. Average measures of inter-observer reproducibility of regional metrics.
95% Confidence interval Metric
Interclass correlation
Lower bound
Upper bound
Cronbach’s alpha
p-value
REF-TC REF-AC Mean-RMV Max-RMV
0.966 0.949 0.973 0.954
0.941 0.921 0.959 0.928
0.979 0.967 0.983 0.970
0.969 0.949 0.974 0.956
p < 0.001 p < 0.001 p < 0.001 p < 0.001
4. Discussion and conclusions We investigated a novel method of assessment of the regional function of the left atrium (LA) based on the reconstruction of 3D LA geometry from a stack of cardiac magnetic resonance imaging (MRI) images. The main findings of this study are: (1) decreased mechanical function of the LA in patients with PAF and (2) significantly higher mechanical function of the anterior, septal and lateral regions as opposed to roof and posterior regions in both groups. Those findings are consistent with our previous study in which we used CARTO 3D electrophysiological mapping system to assess regional motion of the LA (Kuklik et al 2010). Temporal changes in regional volumes did not exhibit multi-phase properties as seen in Doppler ultrasound imaging (Thomas et al 2003) (peaks corresponding with systolic peak velocity, early diastolic left ventricular relaxation and the peak velocity in late diastole secondary to atrial contraction). Instead, we observed uni-phasic profile corresponding with a whole chamber contraction (see figure 2). Since we observed a similar profile of volumetric changes in our previous study using a 3D electrophysiological mapping system (Kuklik et al 2010) and in results obtained by others (Raman et al 2005, Marui et al 2008), we suggest that such a profile may be characteristic to analysis of volumetric changes of whole regions of the chamber as opposed to the focal measurements obtained using Doppler ultrasound methods (methods using ultrasound imaging focus on small areas as a representation of the function of the greater region (Matsumoto et al 2006)). We found a difference between two proposed measures of regional volumetric changes: REF-TC (related to global changes) and REF-AC (changes related to active atrial contraction). The difference between both measures reflects a ventricular contribution to atrial volumetric changes. In overall, REF had a similar distribution across regions (see figure 5). However, in REF-TC anterior, septal and lateral regions had a markedly higher contribution than roof and posterior. In REF-AC, only anterior and septal had a markedly higher contribution. This may suggest that the contribution of the lateral region during the active phase of contraction is not reflected in regional volumetric change. The velocity of the predefined atrial regions assessed by segmental colour Doppler imaging resulted in a similar range of regional velocities as reported by Thomas et al (2003). Unfortunately, an exact comparison is difficult due to differences in definition of the regions. A simple comparison shows accordance with our study with respect to the superior region having the lowest velocity but a contrasting result with regard to the posterior aspect, which in our study had a similar range of velocities to the superior aspect (roof segment in our study). This difference may be explained by the translational motion of the atrium which is not taken into account in the Doppler imaging method. Cardiac MRI has previously been used to assess regional atrial mechanical function (Nori et al 2009). Nori et al (2009) used Siemens graphic tools on cardiac MRI to assess regional LA function measuring displacement of reference points throughout the atrial cycle. In contrast 771
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to our findings, they observed no difference between regional function in the control and PAF groups, which could possibly be related to the use of a single image and arbitrary reference point as a chamber centre to assess function of the whole region. In our approach we assess the motion of the atrial wall in 3D with respect to the geometrical centre of the reconstructed chamber which can be the reason for the difference in findings. We applied two types of metrics quantifying the regional mechanical function of the atria: regional ejection fraction (REF, based either on a total cycle or just on the active phase of the contraction) and region motion velocity (RMV). Both metrics are based on the geometrical properties of a predefined region of the atrial wall displacement. REF is based on volumetric changes with respect to the centre of the chamber and as such takes into account the translational motion of the LA. RMV, however, reflects an absolute velocity of the wall throughout contraction and is therefore affected by translational motion. As measures constructed on 3D geometry, both metrics take the geometrical orientation of the wall with respect to the displacement direction. Several other metrics have been proposed to date, with specific features depending on the modality employed. With respect to a quantified property, two groups can be identified: metrics quantifying regional muscle contractility (based on echocardiographic imaging) and metrics quantifying atrial wall motion. Our metrics fall into the latter category. Contractility and strain imaging using MR is possible (Herbots et al 2004); however, these are difficult in atrial muscle due to low tissue volume and therefore signal intensity insufficient to derive such metrics. Since there is no clear link between muscle strain and its motion in 3D, we were unable to estimate these measures. With respect to metrics assessing regional wall motion, two general approaches are reported: analysis of atrial wall displacement (e.g. Nori et al 2009) or velocity (e.g. Henein et al 2012, Sun et al 2013, Kojima et al 2012). Nori et al (2009) used a radial fractional shortening metric of the selected atrial region as a metric of its function, which is analogous to the REF metric (quantifying the change of the region position through the cycle), but implemented just in one slice of the MR image. However, Nori et al (2009) used the mid-point of the segment as a spatial reference of the region position, unlike the REF metric which uses the entire region surface to compute fractional change. Velocity based metrics derived from echocardiographic imaging such as those reported in Sun et al (2013) average wall motion velocity taking into account the entire region of interest, similarly to the RMV parameter presented in this study. Unfortunately due to differences in segment definitions we are unable to compare results. The findings of our study may be used in clinical practice in designing an AF ablation strategy. Studies suggest that there are two contributing factors to LA function changes following ablation: the amount of ablated tissue and gradual improvement of atrial ejection fraction after restoration of sinus rhythm (Wylie et al 2008, Schneider et al 2008). The extent of a tissue damage after an AF ablation procedure has been quantified by means of delayed enhancement MRI (McGann et al 2008, Peters et al 2007). Current ablation strategies focus on pulmonary vein isolation (Haissaguerre et al 1998, Chen et al 1999), linear lesions in the LA roof and mitral isthmus (Ernst et al 2003), wide ablation in the posterior LA surrounding pulmonary veins (Ouyang et al 2004) and ablation guided by complexity of cardiac electrograms (Oral et al 2007). Therefore, the greatest damage to atrial tissue can be expected in the atrial roof, posterior, lateral and septal segments, with less damage in the anterior segment. Based on our results, we hypothesize that due to higher regional mechanical function, anterior, septal and lateral regions should receive minimal damage during the ablation procedure to preserve global mechanical function of the atria. This could be achieved by modification of ablation strategies mentioned above by prioritization of ablation locations according to their mechanical function (starting ablation in areas of low 772
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contribution to global mechanical function). Also, preoperative assessment of the LA regional function may allow a patient-specific ablation strategy aiming to avoid ablation in regions having the greatest contribution to global function for a given patient. Such a strategy may decrease the adverse effect of ablation on LA mechanical function and consequently lower the risk of thromboembolic events. Additionally, our results may be useful as one of the sources for validation of mathematical modelling studies (e.g. Di Martino et al 2011) aiming at construction of realistic models of atrial mechanical function. 5. Limitations The presented method was not validated against other imaging modalities. However, it resulted in similar findings which were obtained in our previous study using CARTO 3D mapping system (Kuklik et al 2010). The main limitations of the presented method are: (i) Errors during image segmentation propagate to the surface reconstruction phase introducing artefacts affecting both measures of motion (REF and RMV). An example of such an error is annotation of a neighbouring structure such as a vein as the LA in one of the cardiac phases. This results in an artificial increase of local mechanical function since the algorithm will interpret the sudden appearance and disappearance of the mis-annotated structure during the cycle as motion of the LA surface. Therefore, LA segmentation must be manually supervised and the end result of the reconstruction confirmed. (ii) We assumed that the contribution of a given region to the total mechanical function is reflected by its motion with respect to the geometrical centre of the reconstructed chamber. Since the architecture of the atrial fibre structure is complex, this assumption may not be valid due to the possible long distance effect of local muscle contraction. In such a scenario, ablation at a given point of the chamber may result in an impairment of the mechanical function at a different location. Unfortunately there is no research in this area to shed some light on this problem. (iii) The translational component of the atrial wall movement makes absolute motion of the heart wall inaccurate in assessment of its local mechanical function. We tried to compensate for translational movement by performing calculations referenced to the geometrical centre of the reconstructed chamber. However, due to the inability to reconstruct the total 3D geometry from a single projection there was uncertainty regarding the true geometrical centre of the chamber which could not be determined in this study. (iv) Left atrial mechanical function is strongly affected by ventricular function, especially in the first cardiac phase. Thus, assessment of just motion of the atrial wall may lead to false conclusions regarding the independent function of the atrial muscle. (v) We did not perform validation of our method by comparing with any other imaging modality. This is due to a lack of gold standard in LA regional function assessment. (vi) The 3D model of the atria body is based on the assumption that consecutive MRI images are correctly aligned in space. Spatial orientation of the slices may be affected by patient movement which is difficult to control during scanning. Acknowledgments PK was supported by a fellowship PF no. 10A 5367 from the National Heart Foundation of Australia. PS is supported by the NHMRC Practititioner Fellowship. PM is supported by a Medical Postgraduate Scholarship from the National Health and Medical Research Council of Australia. ANG is supported by NHMRC Australian Early Career Health 773
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Practitioner Fellowship. PP has been supported the European Union under the framework of the European Social Fund through the Warsaw University of Technology Development Program. References Al-Saady N M, Obel O A and Camm A J 1999 Left atrial appendage: structure, function, and role in thromboembolism Heart 82 547–54 Appleton C P, Vianna-Pinton R, Moreno C A, Baxter C M, Lee K S and Tsang T S M 2009 Two-dimensional speckle-tracking echocardiography of the left atrium: feasibility and regional contraction and relaxation differences in normal subjects J. Am. Soc. Echocardiogr. 22 299–305 Bergvall E, Cain P, Arheden H and Sparr G 2006 A fast and highly automated approach to myocardial motion analysis using phase contrast magnetic resonance imaging J. Magn. Reson. Imaging 23 652–61 Chen S A, Hsieh M H, Tai C T, Tsai C F, Prakash V S, Yu W C, Hsu T L, Ding Y A and Chang M S 1999 Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation Circulation 100 1879–86 Chen Y, Wu Z, Yang C, Shao J, Wong K K L and Abbott D 2012 Investigation of atrial vulnerability by analysis of the sinus node EG from atrial fibrillation models using a phase synchronization method IEEE Trans. Biomed. Eng. 59 2668–76 Corsi C, Lang R M, Veronesi F, Weinert L, Caiani E G, Maceneaney P, Lamberti C and Mor-Avi V 2005 Volumetric quantification of global and regional left ventricular function from real-time threedimensional echocardiographic images Circulation 112 1161–70 Di Martino E S, Bellini C and Schwartzman D S 2011 In vivo porcine left atrial wall stress: computational model J. Biomech. 44 2589–94 Ernst S, Ouyang F, Lober F, Antz M and Kuck K H 2003 Catheter-induced linear lesions in the left atrium in patients with atrial fibrillation: an electroanatomic study J. Am. Coll. Cardiol. 42 1271–82 Eusemann C D, Ritman E L, Bellemann M E and Robb R A 2001 Parametric display of myocardial function Comput. Med. Imaging Graph. 25 483–93 Eusemann C D, Ritman E L and Robb R A 2003 Parametric visualization methods for the quantitative assessment of myocardial motion Acad. Radiol. 10 66–76 Gepstein L, Hayam G, Shpun S and Ben-Haim S A 1997 Hemodynamic evaluation of the heart with a nonfluoroscopic electromechanical mapping technique Circulation 96 3672–80 Haissaguerre M, Jais P, Shah D C, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P and Clementy J 1998 Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins N. Engl. J. Med. 339 659–66 Henein M, Zhao Y, Henein M Y and Lindqvist P 2012 Disturbed left atrial mechanical function in paroxysmal atrial fibrillation: a speckle tracking study Int. J. Cardiol. 155 437–41 Herbots L et al 2004 Quantifying myocardial deformation throughout the cardiac cycle: a comparison of ultrasound strain rate, grey-scale M-mode and magnetic resonance imaging Ultrasound Med. Biol. 30 591–8 Ho S Y, Sanchez-Quintana D, Cabrera J A and Anderson R H 1999 Anatomy of the left atrium: implications for radiofrequency ablation of atrial fibrillation J. Cardiovasc. Electrophysiol. 10 1525–33 Kojima T et al 2012 Left atrial global and regional function in patients with paroxysmal atrial fibrillation has already been impaired before enlargement of left atrium: velocity vector imaging echocardiography study Eur. Heart J. Cardiovasc. Imaging 13 227–34 Kuklik P, Molaee P, Brooks A G, John B, Worthley S G and Sanders P 2010 Quantitative description of the regional mechanics of the left atria by electroanatomical mapping Physiol. Meas. 31 555–64 Landini L, Positano V and Santarelli M F 2005 Advanced Image Processing in Magnetic Resonance Imaging (Boca Raton, FL: CRC Press) Lorensen W E and Cline H E 1987 Marching cubes: a high resolution 3D surface construction algorithm Comput. Graph. Forum 21 163–9 Marui A, Saji Y, Nishina T, Tadamura E, Kanao S, Shimamoto T, Sasahashi N, Ikeda T and Komeda M 2008 Impact of left atrial volume reduction concomitant with atrial fibrillation surgery on left atrial geometry and mechanical function J. Thorac. Cardiovasc. Surg. 135 1297–305 774
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Matsumoto K, Ishikawa T, Sumita S, Matsushita K, Inoue N, Kobayashi T, Uchino K, Kimura K and Umemura S 2006 Assessment of atrial regional wall motion using strain doppler imaging during biatrial pacing in the bradycardia-tachycardia syndrome Pace-Pacing Clin. Electrophysiol. 29 220–5 McGann C J et al 2008 New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation J. Am. Coll. Cardiol. 52 1263–71 Moore C C, Lugo-Olivieri C H, Mcveigh E R and Zerhouni E A 2000 Three-dimensional systolic strain patterns in the normal human left ventricle: characterization with tagged MR imaging Radiology 214 453–66 Muellerleile K, Sultan A, Groth M, Steven D, Hoffmann B, Adam G, Lund G K, Rostock T and Willems S 2012 Velocity encoded cardiovascular magnetic resonance to assess left atrial appendage emptying J. Cardiovasc. Magn. Reson. 14 39 Nakazato R et al 2011 Assessment of left ventricular regional wall motion and ejection fraction with low-radiation dose helical dual-source CT: comparison to two-dimensional echocardiography J. Cardiovasc. Comput. Tomogr. 5 149–57 Nori D, Raff G, Gupta V, Gentry R, Boura J and Haines D E 2009 Cardiac magnetic resonance imaging assessment of regional and global left atrial function before and after catheter ablation for atrial fibrillation J. Interv. Card. Electrophysiol. 26 109–17 Oral H et al 2007 Radiofrequency catheter ablation of chronic atrial fibrillation guided by complex electrograms Circulation 115 2606–12 Ouyang F et al 2004 Complete isolation of left atrium surrounding the pulmonary veins: new insights from the double-Lasso technique in paroxysmal atrial fibrillation Circulation 110 2090–6 Peters D C, Wylie J V, Hauser T H, Kissinger K V, Botnar R M, Essebag V, Josephson M E and Manning W J 2007 Detection of pulmonary vein and left atrial scar after catheter ablation with three-dimensional navigator-gated delayed enhancement MR imaging: initial experience Radiology 243 690–5 Raman S V, Ng V Y, Neff M A, Sayar S, Sparks E A, Nelson S D, Ferketich A K and Wooley C F 2005 Volumetric cine CMR to quantify atrial structure and function in patients with atrial dysrhythmias J. Cardiovasc. Magn. Reson. 7 539–43 Sanders P, Morton J B, Kistler P M, Vohra J K, Kalman J M and Sparks P B 2003 Reversal of atrial mechanical dysfunction after cardioversion of atrial fibrillation: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy Circulation 108 1976–84 Schneider C, Malisius R, Krause K, Lampe F, Bahlmann E, Boczor S, Antz M, Ernst S and Kuck K H 2008 Strain rate imaging for functional quantification of the left atrium: atrial deformation predicts the maintenance of sinus rhythm after catheter ablation of atrial fibrillation Eur. Heart J. 29 1397–409 Shen M Y, Liu Y H, Sinusas A J, Fetterman R, Bruni W, Drozhinin O E, Zaret B L and Wackers F J 1999 Quantification of regional myocardial wall thickening on electrocardiogram-gated SPECT imaging J. Nucl. Cardiol. 6 583–95 Slart R H, Bax J J, De Jong R M, De Boer J, Lamb H J, Mook P H, Willemsen A T, Vaalburg W, Van Veldhuisen D J and Jager P L 2004 Comparison of gated PET with MRI for evaluation of left ventricular function in patients with coronary artery disease J. Nucl. Med. 45 176–82 Stefanadis C, Dernellis J and Toutouzas P 2001 A clinical appraisal of left atrial function Eur. Heart J. 22 22–36 Sun J P, Yang Y, Guo R, Wang D, Lee A P, Wang X Y, Lam Y Y, Fang F, Yang X S and Yu C M 2013 Left atrial regional phasic strain, strain rate and velocity by speckle-tracking echocardiography: Normal values and effects of aging in a large group of normal subjects Int. J. Cardiol. 168 3473–9 Thomas L 2007 Assessment of atrial function Heart Lung Circ. 16 234–42 Thomas L, Levett K, Boyd A, Leung D Y, Schiller N B and Ross D L 2003 Changes in regional left atrial function with aging: evaluation by Doppler tissue imaging Eur. J. Echocardiogr. 4 92–100 Wong K K L, Kelso R M, Worthley S G, Sanders P, Mazumdar J and Abbott D 2009 Cardiac flow analysis applied to phase contrast magnetic resonance imaging of the heart Ann. Biomed. Eng. 37 1495–515 Wylie J V Jr, Peters D C, Essebag V, Manning W J, Josephson M E and Hauser T H 2008 Left atrial function and scar after catheter ablation of atrial fibrillation Heart Rhythm. 5 656–62 Zipes D P and Jalife J 2004 Cardiac Electrophysiology: From Cell to Bedside (Philadelphia, PA: Saunders)
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Quantitative description of the 3D regional mechanics of the left atrium using cardiac magnetic resonance imaging To cite this article: P Kuklik et al 2014 Physiol. Meas. 35 763
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Institute of Physics and Engineering in Medicine Physiol. Meas. 35 (2014) 763–775
Physiological Measurement
doi:10.1088/0967-3334/35/5/763
Quantitative description of the 3D regional mechanics of the left atrium using cardiac magnetic resonance imaging P Kuklik 1 , P Molaee 1 , P Podziemski 2 , A N Ganesan 1 , A G Brooks 1 , S G Worthley 1 and P Sanders 1 1
Centre for Heart Rhythm Disorders (CHRD), South Australian Health and Medical Research Institute (SAHMRI), University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia 2 Faculty of Physics, Warsaw University of Technology, Warsaw, Poland E-mail: [email protected] Received 19 August 2013, revised 25 February 2014 Accepted for publication 28 February 2014 Published 26 March 2014 Abstract
The left atrium (LA) plays an important role in the maintenance of hemodynamic and electrical stability of the heart. One of the conditions altering the atrial mechanical function is atrial fibrillation (AF), leading to an increased thromboembolic risk due to impaired mechanical function. Preserving the regions of the LA that contribute the greatest to atrial mechanical function during curative strategies for AF is important. The purpose of this study is to introduce a novel method of regional assessment of mechanical function of the LA. We used cardiac MRI to reconstruct the 3D geometry of the LA in nine control and nine patients with paroxysmal atrial fibrillation (PAF). Regional mechanical function of the LA in pre-defined segments of the atrium was calculated using regional ejection fraction and wall velocity. We found significantly greater mechanical function in anterior, septal and lateral segments as opposed to roof and posterior segments, as well as a significant decrease of mechanical function in the PAF group. We suggest that in order to minimize the impact of the AF treatment on global atrial mechanical function, damage related to therapeutic intervention, such as catheter ablation, in those areas should be minimized. Keywords: atrial mechanical function, atrial fibrillation, AF ablation, 3D reconstruction, cardiac MRI S Online supplementary data available from stacks.iop.org/PM/35/763/mmedia
(Some figures may appear in colour only in the online journal) 0967-3334/14/050763+13$33.00
© 2014 Institute of Physics and Engineering in Medicine Printed in the UK
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1. Introduction The mechanical function of the left atrium (LA) plays an important role in hemodynamic function of the heart. Impaired LA mechanical function results in an increased risk of thromboembolic events due to impaired flow in the LA appendage (Al-Saady et al 1999). One of the most prevalent causes of impaired LA function is atrial fibrillation (AF)—a complex disturbance of the conduction of the electrochemical waves in the atria resulting in a lack of coordinated global mechanical function (Zipes and Jalife 2004). Since termination of AF was shown to improve atrial mechanical function (Sanders et al 2003), the restoration of sinus rhythm has become an important clinical target. One of the ways of restoring sinus rhythm in AF is an ablation procedure, during which a set of catheters is introduced into the atria and areas responsible for maintenance of the arrhythmia are targeted and destroyed. In the case of chronic AF, the amount of ablation required to terminate arrhythmia is significant, contributing to the deterioration of LA function (Wylie et al 2008). In order to minimize the detrimental impact of ablation on global LA function, the damage should be minimized in areas crucial for mechanical function. In this study, we aimed to characterize a novel method to quantify the regional mechanical function of the LA, and in order to identify the regions contributing the greatest mechanical function. Current methods of cardiac mechanical function assessment are based on imaging methods such as computed tomography (Nakazato et al 2011), magnetic resonance imaging (MRI) (Bergvall et al 2006, Moore et al 2000), magnetic resonance velocitometry (Wong et al 2009), positron emission tomography (Shen et al 1999, Slart et al 2004), echocardiography (Thomas 2007, Corsi et al 2005) and catheterization (Gepstein et al 1997). Regional function of the atria has been assessed using several approaches (Stefanadis et al 2001) including: pulsed wave and colour Doppler tissue imaging (Thomas et al 2003), two-dimensional speckle-tracking echocardiography (Appleton et al 2009, Sun et al 2013, Henein et al 2012), velocity vector imaging (Kojima et al 2012), strain Doppler imaging (Matsumoto et al 2006), cardiac MRI (Nori et al 2009, Muellerleile et al 2012) and three-dimensional (3D) electrophysiological mapping systems (Kuklik et al 2010, Chen et al 2012). Ultrasound-based methods characterize regional function through analysis of the motion of a fixed point in a given region, thus not providing the true average function of the whole region. 3D electrophysiological mapping system approaches characterize the motion of whole regions; however, these require the introduction of catheters, which may not be feasible in practice. Colour Doppler tissue imaging and speckle-tracking (e.g. Thomas et al 2003), despite obvious advantages (low cost and noninvasive in nature), have significant limitations, including angle-dependence of tissue and issues with poor reproducibility between investigators. In this study, we aim to strengthen the above methods of regional function assessment using cardiac MRI imaging of the LA to reconstruct the 3D geometry of the chamber and quantify regional motion of the atrial walls using the concept of regional ejection fraction and regional wall velocity.
2. Methods 2.1. Patient characteristics
MRI cine images of nine patients with paroxysmal atrial fibrillation (PAF) were analysed with a reference group of nine patients with structurally normal hearts undergoing radiofrequency ablation for atrioventricular re-entry tachycardia with left-sided accessory pathways and no history of AF. Six males and three females were in each group with the mean age for the 764
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control group 58 ± 6 and 67 ± 7 for the PAF group. All patients provided written informed consent for their procedures. 2.2. MRI imaging protocol
All patients underwent cardiac MRI at 1.5 T (Siemens Avanto, Siemens Medical Solutions, Erlangen, Germany) during sinus rhythm. Sequential steady-state free-precession short-axis cine sequences were acquired with 1.2 mm in-plane resolution, 6 mm slice thickness and no interslice gaps through the atrium in short axis (SA) and four chamber view (4C) orientations. Slices were taken from the most cranial aspect of the LA and sequentially to the cardiac apex at end-expiration. 2.3. Image segmentation
Segmentation of the atrium from MRI images was performed using a region growing algorithmbased on pixel intensity. The algorithm starts from an initial seed pointed by the operator and grows until the segmented part of the image is surrounded by pixels of intensity lower by one standard deviation of intensity from the average intensity of pixels within the currently segmented region. Segmentation was manually supervised and corrected in case of an overflow to neighbouring structures (e.g. due to lack of a clearly defined boundary between the LA and right atrium) or scanning artefacts. Segmentation was performed for all images in SA and 4C orientations and at each point of the cycle (25 time points in cycle) taking around 30 min per patient. 2.4. Construction of a 3D grid
Due to the geometrical non-uniformity of the initial dataset (in-plane image resolution was 1.2 mm with a 6 mm gap between images), we transformed it into a uniform grid which was later used as a starting point for surface reconstruction. After assessing the effect of a voxel size on obtained chamber volume (see figure 1 in the supplementary materials, available from stacks.iop.org/PMEA/35/763/mmedia), due to the lack of a clear plateau, we selected a value of 2 mm. Intensities of the 3D grid elements Igrid(i, j,k) were obtained by interpolation of the intensities of the MRI image pixels: I grid (i, j, k) = (1 − λ)I MRI (i , j , k ) + λI MRI (i , j , k )
(1)
where I denotes intensity, (i , j , k ) are coordinates of the closest pixel in a stack of MRI images where k denotes an image index in a stack. k is the index of the second closest image. λ is a coefficient calculated using distances to the two closest MRI images in a stack: dist({i, j, k}, {i , j , k }) (2) λ= dist({i , j , k }, {i , j , k }) where dist({i, j, k}, {i , j , k }) is the Euclidean distance between elements {i, j, k} and {i , j , k } in 3D space. In other words, cine images were upsampled to a spatially uniform volumetric grid, using linear interpolation. 2.5. Surface reconstruction
The endocardial surface was reconstructed based on the 3D volume model using the marching cubes algorithm (Lorensen and Cline 1987) resulting in a triangularized endocardial surface of the atrium. Surface smoothing was performed by averaging the spatial coordinates of each surface node. An example of the reconstruction is shown in figure 1. 765
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(a)
(b)
(c)
(d)
Figure 1. Example reconstruction of the geometry of the LA. Stack of MRI images with segmented areas of LA in black stripes (a). Volume model of the LA (b). Reconstructed surface (c). Surface after applying the smoothing algorithm (d).
2.6. Atrium segmentation
The LA surface was manually segmented into six distinct segments: anterior, lateral, roof, septal, posterior and inferior segment (Ho et al 1999) (see figure 2). Anterior, lateral, septal and posterior segments were reconstructed using the SA projection and the function of the roof segment was assessed using the 4C projection. Segmentation of the chamber was performed manually at the first point of the cardiac cycle and then regions were propagated to the remaining phases of the cycle according to the following equation: Segment Tin = Segment min(d Tin , Tjn−1 j
(3)
where Segment(T) is a function returning a segment identifier for a given triangle Ti of the surface in phase n (n is a number between 0 and 24 corresponding to the cardiac phase). Function d is a Euclidean distance between the geometrical centres of two triangles. In simpler words, to find a segment identifier for a given triangle, the closest triangle in the preceding phase is located and its segment identifier copied. 766
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(a)
(b)
(c)
Figure 2. Example of the LA segmentation. For each cardiac phase, the LA was segmented into six distinct segments. Segments obtained from the short axis projection (a). Roof segment obtained from the four chamber projection (b). The segmental volume taken by each segment is then calculated for each cardiac phase resulting in a plot depicting segmental volume throughout the whole cycle (c).
2.7. Metrics used to quantify the mechanical function of the atrial wall
Since MRI cine images provide the position of the atrial wall throughout the cardiac cycle, metrics quantifying mechanical function have to be based on this information. The position of the atrial wall in space throughout the cardiac cycle enables the construction of two general types of metrics: (i) a metric based on a velocity of the atrial wall and (ii) a metric-based on a volume of space occupied by a given region of the surface throughout the cycle. Those two metrics may result in different estimates since volumetric change depends on the geometrical shape of the surface (two surfaces moving with the same velocity may result in a different occupied volume depending on their shape). In order to assess the regional mechanical function of the LA, we used the concept of a regional ejection fraction (REF) parameter as defined in Kuklik et al (2010). REF is defined using a segmental volume assessing the relative contribution of a given region of the chamber towards the global volume of the chamber. Segmental volume is defined as a cone with a vertex located in the geometrical centre of the reconstructed chamber (calculated at each phase of the cycle to account for translational motion of the chamber) and a base defined by a surface of the given region (e.g. anterior LA) (see figure 3). The volume of each cone changes throughout the heart cycle, providing a measure of the contribution
2.7.1. Regional ejection fraction.
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Figure 3. Definition of regional systolic and diastolic volume. C is located at the geometrical centre of the chamber. Ssystolic and Sdiastolic denote a portion of the endocardial surface defined as a given region in systole and diastole, respectively. Regional volume is defined as the volume of a solid defined by a vertex C and surface S.
of a given region towards global volumetric changes of whole chamber at each point of the cycle. For each region of the LA, segmental volume was calculated for all phases of the cycle. Two types of REF parameters were used: REF-TC related to the total contraction and REFAC related to an active component of contraction. REF-TC was defined using the following equation: Vdiastolic − Vsystolic (4) REF − TC = Vdiastolic where Vdiastolic is a segmental volume taken by a given segment in diastole, and Vsystolic is a segmental volume in systole. The second parameter (REF-AC) is related to an active component of a contraction and is defined using segmental volumes at the phase of the cycle related to the greatest volume and 18th phase of the cycle. REF-AC is defined using the following equation: Vdiastolic − V18 (5) Vdiastolic where Vdiastolic is the maximum segmental volume, and V18 the segmental volume during the 18th phase of the cycle. Both parameters reflect regional volumetric changes related to chamber contraction. REF-TC reflects the total volumetric change between systole and diastole. However, volumetric change between systole and diastole includes atrial passive filling and is therefore not specifically related to an active phase of atrial contraction. In order to reflect the volumetric changes related to atrial contraction, REF-AC was devised as a difference between the diastolic and 18th phase of the cycle (the 18th phase was selected as the middle of the plateau in the regional volumetric plot following active atrial contraction, see figure 2). REF − AC =
The motion of the endocardial surface was previously characterized and assessed in several studies (Landini et al 2005, Eusemann et al 2001, 2003). Based on those studies we introduced a second parameter to quantify the mechanical function of a given atrial region: region motion velocity (RMV). In order to calculate RMV, the velocity for each triangle of the surface within a given segment is calculated. The velocity of the triangle is defined as a ratio of the distance between the centre of a given triangle and the chamber surface in the next time point (phase) and time interval. Then, RMV is calculated
2.7.2. Region motion velocity.
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Figure 4. Example distribution of the regional motion velocity (RMV) in the anterior view of the LA. Left map shows the distribution of maximum RMV value. Right map shows the averaged value throughout the cardiac cycle.
as a mean of the velocities of the triangles belonging to a given region. Two parameters are calculated for each region using RMV: maximum-RMV (maximum RMV throughout the cycle) and mean-RMV (mean RMV throughout the cycle). An example of the spatial distribution of the RMV is shown in figure 4. 2.8. Inter-observer variability
Two independent and experienced investigators performed LA segmentation and analysis in order to establish an inter-observer agreement. The agreement was assessed via intra-class correlation coefficients (ICCs) with 95% limits of agreement. Absolute ICCs agreement was calculated via a two way random effects model. 2.9. Statistical analysis
Data are presented as a mean ± standard deviation. All variables were compared using a linear mixed effects model, with fixed effects of anatomical region (n = 6) and group (n = 2) and their interaction. Age and patient id were introduced as random variables. If the interaction term was not significant, the model was run again without the interaction term to examine the main effects. Post hoc tests for segments were conducted with Sidak confidence interval adjustment. Statistical significance was established at p < 0.05. Statistical analyses were performed in SPSS version 19 (IBM Corporation, Armonk, NY). 3. Results LA geometry was reconstructed for each patient in SA and 4C view followed by segmentation and calculation of regional volumetric changes and wall velocities. An example of a time course of regional volumes is shown in figure 2. An example of the motion of the reconstructed surface is shown in the movies in the supplementary materials (available online at stacks.iop.org/PMEA/35/763/mmedia). REF-TC and REF-AC for distinct segments of the LA are shown in figures 5(a) and (b). Both REF parameters were significantly higher in the control group as compared to the PAF group (p < 0.001 for REF-TC and p < 0.005 for REF-AC). Mean REF-TC in the control group was 0.51 ± 0.19 versus 0.4 ± 0.18 in the PAF group. Mean REF-AC in the control group was 0.21 ± 0.15 versus 0.15 ± 0.12 in the PAF group. 769
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(a)
(c)
(b)
(d)
Figure 5. Regional ejection fraction related to total contraction (REF-TC) (a), regional ejection fraction related to an active component of contraction (REF-AC) (b), mean region motion velocity (mean-RMV) (c) and maximum region motion velocity (maxRMV) (d) for distinct segments of the LA for the control group (n = 9) and the paroxysmal atrial fibrillation group (n = 9). Error bars denote ± 1 SD.
Mean-RMV and max-RMV for distinct segments of the LA are shown in figures 5(c) and (d). Both RMV parameters were significantly higher in the control group as compared to the PAF group (p < 0.001 for mean-RMV and p < 0.01 for max-RMV). Mean-RMV in the control group was 0.028 ± 0.009 m s−1 versus 0.023 ± 0.007 m s−1 in the PAF group. Max-RMV in the control group was 0.059 ± 0.028 m s−1 versus 0.048 ± 0.022 m s−1 in the PAF group. A significant regional variation for all parameters (REF-TC, REF-AC, mean-RMV and max-RMV) was observed (p < 0.001). For REF-TC, REF-AC and mean-RMV roof and posterior segments were associated with lower values as compared to anterior, septal and lateral segments (p < 0.01). For max-RMV roof, posterior and lateral segments had lower values as compared to anterior and septal (p < 0.01). The non-significant (p = 0.77 for REF-TC, p = 0.11 for REF-AC, p = 0.69 for mean-RMV and p = 0.94 for max-RMV) group∗ region interaction term demonstrated that the pattern of parameters was the same in the PAF and control groups. In overall, inter-observer reliability of regional analysis was high with ICC > 0.94 and Cronbach’s α > 0.95 (see table 1). The lowest ICC was found for REF-AC metric (ICC = 0.949) and the highest with mean-RMV (ICC = 0.973). 770
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Table 1. Average measures of inter-observer reproducibility of regional metrics.
95% Confidence interval Metric
Interclass correlation
Lower bound
Upper bound
Cronbach’s alpha
p-value
REF-TC REF-AC Mean-RMV Max-RMV
0.966 0.949 0.973 0.954
0.941 0.921 0.959 0.928
0.979 0.967 0.983 0.970
0.969 0.949 0.974 0.956
p < 0.001 p < 0.001 p < 0.001 p < 0.001
4. Discussion and conclusions We investigated a novel method of assessment of the regional function of the left atrium (LA) based on the reconstruction of 3D LA geometry from a stack of cardiac magnetic resonance imaging (MRI) images. The main findings of this study are: (1) decreased mechanical function of the LA in patients with PAF and (2) significantly higher mechanical function of the anterior, septal and lateral regions as opposed to roof and posterior regions in both groups. Those findings are consistent with our previous study in which we used CARTO 3D electrophysiological mapping system to assess regional motion of the LA (Kuklik et al 2010). Temporal changes in regional volumes did not exhibit multi-phase properties as seen in Doppler ultrasound imaging (Thomas et al 2003) (peaks corresponding with systolic peak velocity, early diastolic left ventricular relaxation and the peak velocity in late diastole secondary to atrial contraction). Instead, we observed uni-phasic profile corresponding with a whole chamber contraction (see figure 2). Since we observed a similar profile of volumetric changes in our previous study using a 3D electrophysiological mapping system (Kuklik et al 2010) and in results obtained by others (Raman et al 2005, Marui et al 2008), we suggest that such a profile may be characteristic to analysis of volumetric changes of whole regions of the chamber as opposed to the focal measurements obtained using Doppler ultrasound methods (methods using ultrasound imaging focus on small areas as a representation of the function of the greater region (Matsumoto et al 2006)). We found a difference between two proposed measures of regional volumetric changes: REF-TC (related to global changes) and REF-AC (changes related to active atrial contraction). The difference between both measures reflects a ventricular contribution to atrial volumetric changes. In overall, REF had a similar distribution across regions (see figure 5). However, in REF-TC anterior, septal and lateral regions had a markedly higher contribution than roof and posterior. In REF-AC, only anterior and septal had a markedly higher contribution. This may suggest that the contribution of the lateral region during the active phase of contraction is not reflected in regional volumetric change. The velocity of the predefined atrial regions assessed by segmental colour Doppler imaging resulted in a similar range of regional velocities as reported by Thomas et al (2003). Unfortunately, an exact comparison is difficult due to differences in definition of the regions. A simple comparison shows accordance with our study with respect to the superior region having the lowest velocity but a contrasting result with regard to the posterior aspect, which in our study had a similar range of velocities to the superior aspect (roof segment in our study). This difference may be explained by the translational motion of the atrium which is not taken into account in the Doppler imaging method. Cardiac MRI has previously been used to assess regional atrial mechanical function (Nori et al 2009). Nori et al (2009) used Siemens graphic tools on cardiac MRI to assess regional LA function measuring displacement of reference points throughout the atrial cycle. In contrast 771
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to our findings, they observed no difference between regional function in the control and PAF groups, which could possibly be related to the use of a single image and arbitrary reference point as a chamber centre to assess function of the whole region. In our approach we assess the motion of the atrial wall in 3D with respect to the geometrical centre of the reconstructed chamber which can be the reason for the difference in findings. We applied two types of metrics quantifying the regional mechanical function of the atria: regional ejection fraction (REF, based either on a total cycle or just on the active phase of the contraction) and region motion velocity (RMV). Both metrics are based on the geometrical properties of a predefined region of the atrial wall displacement. REF is based on volumetric changes with respect to the centre of the chamber and as such takes into account the translational motion of the LA. RMV, however, reflects an absolute velocity of the wall throughout contraction and is therefore affected by translational motion. As measures constructed on 3D geometry, both metrics take the geometrical orientation of the wall with respect to the displacement direction. Several other metrics have been proposed to date, with specific features depending on the modality employed. With respect to a quantified property, two groups can be identified: metrics quantifying regional muscle contractility (based on echocardiographic imaging) and metrics quantifying atrial wall motion. Our metrics fall into the latter category. Contractility and strain imaging using MR is possible (Herbots et al 2004); however, these are difficult in atrial muscle due to low tissue volume and therefore signal intensity insufficient to derive such metrics. Since there is no clear link between muscle strain and its motion in 3D, we were unable to estimate these measures. With respect to metrics assessing regional wall motion, two general approaches are reported: analysis of atrial wall displacement (e.g. Nori et al 2009) or velocity (e.g. Henein et al 2012, Sun et al 2013, Kojima et al 2012). Nori et al (2009) used a radial fractional shortening metric of the selected atrial region as a metric of its function, which is analogous to the REF metric (quantifying the change of the region position through the cycle), but implemented just in one slice of the MR image. However, Nori et al (2009) used the mid-point of the segment as a spatial reference of the region position, unlike the REF metric which uses the entire region surface to compute fractional change. Velocity based metrics derived from echocardiographic imaging such as those reported in Sun et al (2013) average wall motion velocity taking into account the entire region of interest, similarly to the RMV parameter presented in this study. Unfortunately due to differences in segment definitions we are unable to compare results. The findings of our study may be used in clinical practice in designing an AF ablation strategy. Studies suggest that there are two contributing factors to LA function changes following ablation: the amount of ablated tissue and gradual improvement of atrial ejection fraction after restoration of sinus rhythm (Wylie et al 2008, Schneider et al 2008). The extent of a tissue damage after an AF ablation procedure has been quantified by means of delayed enhancement MRI (McGann et al 2008, Peters et al 2007). Current ablation strategies focus on pulmonary vein isolation (Haissaguerre et al 1998, Chen et al 1999), linear lesions in the LA roof and mitral isthmus (Ernst et al 2003), wide ablation in the posterior LA surrounding pulmonary veins (Ouyang et al 2004) and ablation guided by complexity of cardiac electrograms (Oral et al 2007). Therefore, the greatest damage to atrial tissue can be expected in the atrial roof, posterior, lateral and septal segments, with less damage in the anterior segment. Based on our results, we hypothesize that due to higher regional mechanical function, anterior, septal and lateral regions should receive minimal damage during the ablation procedure to preserve global mechanical function of the atria. This could be achieved by modification of ablation strategies mentioned above by prioritization of ablation locations according to their mechanical function (starting ablation in areas of low 772
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contribution to global mechanical function). Also, preoperative assessment of the LA regional function may allow a patient-specific ablation strategy aiming to avoid ablation in regions having the greatest contribution to global function for a given patient. Such a strategy may decrease the adverse effect of ablation on LA mechanical function and consequently lower the risk of thromboembolic events. Additionally, our results may be useful as one of the sources for validation of mathematical modelling studies (e.g. Di Martino et al 2011) aiming at construction of realistic models of atrial mechanical function. 5. Limitations The presented method was not validated against other imaging modalities. However, it resulted in similar findings which were obtained in our previous study using CARTO 3D mapping system (Kuklik et al 2010). The main limitations of the presented method are: (i) Errors during image segmentation propagate to the surface reconstruction phase introducing artefacts affecting both measures of motion (REF and RMV). An example of such an error is annotation of a neighbouring structure such as a vein as the LA in one of the cardiac phases. This results in an artificial increase of local mechanical function since the algorithm will interpret the sudden appearance and disappearance of the mis-annotated structure during the cycle as motion of the LA surface. Therefore, LA segmentation must be manually supervised and the end result of the reconstruction confirmed. (ii) We assumed that the contribution of a given region to the total mechanical function is reflected by its motion with respect to the geometrical centre of the reconstructed chamber. Since the architecture of the atrial fibre structure is complex, this assumption may not be valid due to the possible long distance effect of local muscle contraction. In such a scenario, ablation at a given point of the chamber may result in an impairment of the mechanical function at a different location. Unfortunately there is no research in this area to shed some light on this problem. (iii) The translational component of the atrial wall movement makes absolute motion of the heart wall inaccurate in assessment of its local mechanical function. We tried to compensate for translational movement by performing calculations referenced to the geometrical centre of the reconstructed chamber. However, due to the inability to reconstruct the total 3D geometry from a single projection there was uncertainty regarding the true geometrical centre of the chamber which could not be determined in this study. (iv) Left atrial mechanical function is strongly affected by ventricular function, especially in the first cardiac phase. Thus, assessment of just motion of the atrial wall may lead to false conclusions regarding the independent function of the atrial muscle. (v) We did not perform validation of our method by comparing with any other imaging modality. This is due to a lack of gold standard in LA regional function assessment. (vi) The 3D model of the atria body is based on the assumption that consecutive MRI images are correctly aligned in space. Spatial orientation of the slices may be affected by patient movement which is difficult to control during scanning. Acknowledgments PK was supported by a fellowship PF no. 10A 5367 from the National Heart Foundation of Australia. PS is supported by the NHMRC Practititioner Fellowship. PM is supported by a Medical Postgraduate Scholarship from the National Health and Medical Research Council of Australia. ANG is supported by NHMRC Australian Early Career Health 773
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Practitioner Fellowship. PP has been supported the European Union under the framework of the European Social Fund through the Warsaw University of Technology Development Program. References Al-Saady N M, Obel O A and Camm A J 1999 Left atrial appendage: structure, function, and role in thromboembolism Heart 82 547–54 Appleton C P, Vianna-Pinton R, Moreno C A, Baxter C M, Lee K S and Tsang T S M 2009 Two-dimensional speckle-tracking echocardiography of the left atrium: feasibility and regional contraction and relaxation differences in normal subjects J. Am. Soc. Echocardiogr. 22 299–305 Bergvall E, Cain P, Arheden H and Sparr G 2006 A fast and highly automated approach to myocardial motion analysis using phase contrast magnetic resonance imaging J. Magn. Reson. Imaging 23 652–61 Chen S A, Hsieh M H, Tai C T, Tsai C F, Prakash V S, Yu W C, Hsu T L, Ding Y A and Chang M S 1999 Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation Circulation 100 1879–86 Chen Y, Wu Z, Yang C, Shao J, Wong K K L and Abbott D 2012 Investigation of atrial vulnerability by analysis of the sinus node EG from atrial fibrillation models using a phase synchronization method IEEE Trans. Biomed. Eng. 59 2668–76 Corsi C, Lang R M, Veronesi F, Weinert L, Caiani E G, Maceneaney P, Lamberti C and Mor-Avi V 2005 Volumetric quantification of global and regional left ventricular function from real-time threedimensional echocardiographic images Circulation 112 1161–70 Di Martino E S, Bellini C and Schwartzman D S 2011 In vivo porcine left atrial wall stress: computational model J. Biomech. 44 2589–94 Ernst S, Ouyang F, Lober F, Antz M and Kuck K H 2003 Catheter-induced linear lesions in the left atrium in patients with atrial fibrillation: an electroanatomic study J. Am. Coll. Cardiol. 42 1271–82 Eusemann C D, Ritman E L, Bellemann M E and Robb R A 2001 Parametric display of myocardial function Comput. Med. Imaging Graph. 25 483–93 Eusemann C D, Ritman E L and Robb R A 2003 Parametric visualization methods for the quantitative assessment of myocardial motion Acad. Radiol. 10 66–76 Gepstein L, Hayam G, Shpun S and Ben-Haim S A 1997 Hemodynamic evaluation of the heart with a nonfluoroscopic electromechanical mapping technique Circulation 96 3672–80 Haissaguerre M, Jais P, Shah D C, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P and Clementy J 1998 Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins N. Engl. J. Med. 339 659–66 Henein M, Zhao Y, Henein M Y and Lindqvist P 2012 Disturbed left atrial mechanical function in paroxysmal atrial fibrillation: a speckle tracking study Int. J. Cardiol. 155 437–41 Herbots L et al 2004 Quantifying myocardial deformation throughout the cardiac cycle: a comparison of ultrasound strain rate, grey-scale M-mode and magnetic resonance imaging Ultrasound Med. Biol. 30 591–8 Ho S Y, Sanchez-Quintana D, Cabrera J A and Anderson R H 1999 Anatomy of the left atrium: implications for radiofrequency ablation of atrial fibrillation J. Cardiovasc. Electrophysiol. 10 1525–33 Kojima T et al 2012 Left atrial global and regional function in patients with paroxysmal atrial fibrillation has already been impaired before enlargement of left atrium: velocity vector imaging echocardiography study Eur. Heart J. Cardiovasc. Imaging 13 227–34 Kuklik P, Molaee P, Brooks A G, John B, Worthley S G and Sanders P 2010 Quantitative description of the regional mechanics of the left atria by electroanatomical mapping Physiol. Meas. 31 555–64 Landini L, Positano V and Santarelli M F 2005 Advanced Image Processing in Magnetic Resonance Imaging (Boca Raton, FL: CRC Press) Lorensen W E and Cline H E 1987 Marching cubes: a high resolution 3D surface construction algorithm Comput. Graph. Forum 21 163–9 Marui A, Saji Y, Nishina T, Tadamura E, Kanao S, Shimamoto T, Sasahashi N, Ikeda T and Komeda M 2008 Impact of left atrial volume reduction concomitant with atrial fibrillation surgery on left atrial geometry and mechanical function J. Thorac. Cardiovasc. Surg. 135 1297–305 774
P Kuklik et al
Physiol. Meas. 35 (2014) 763
Matsumoto K, Ishikawa T, Sumita S, Matsushita K, Inoue N, Kobayashi T, Uchino K, Kimura K and Umemura S 2006 Assessment of atrial regional wall motion using strain doppler imaging during biatrial pacing in the bradycardia-tachycardia syndrome Pace-Pacing Clin. Electrophysiol. 29 220–5 McGann C J et al 2008 New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation J. Am. Coll. Cardiol. 52 1263–71 Moore C C, Lugo-Olivieri C H, Mcveigh E R and Zerhouni E A 2000 Three-dimensional systolic strain patterns in the normal human left ventricle: characterization with tagged MR imaging Radiology 214 453–66 Muellerleile K, Sultan A, Groth M, Steven D, Hoffmann B, Adam G, Lund G K, Rostock T and Willems S 2012 Velocity encoded cardiovascular magnetic resonance to assess left atrial appendage emptying J. Cardiovasc. Magn. Reson. 14 39 Nakazato R et al 2011 Assessment of left ventricular regional wall motion and ejection fraction with low-radiation dose helical dual-source CT: comparison to two-dimensional echocardiography J. Cardiovasc. Comput. Tomogr. 5 149–57 Nori D, Raff G, Gupta V, Gentry R, Boura J and Haines D E 2009 Cardiac magnetic resonance imaging assessment of regional and global left atrial function before and after catheter ablation for atrial fibrillation J. Interv. Card. Electrophysiol. 26 109–17 Oral H et al 2007 Radiofrequency catheter ablation of chronic atrial fibrillation guided by complex electrograms Circulation 115 2606–12 Ouyang F et al 2004 Complete isolation of left atrium surrounding the pulmonary veins: new insights from the double-Lasso technique in paroxysmal atrial fibrillation Circulation 110 2090–6 Peters D C, Wylie J V, Hauser T H, Kissinger K V, Botnar R M, Essebag V, Josephson M E and Manning W J 2007 Detection of pulmonary vein and left atrial scar after catheter ablation with three-dimensional navigator-gated delayed enhancement MR imaging: initial experience Radiology 243 690–5 Raman S V, Ng V Y, Neff M A, Sayar S, Sparks E A, Nelson S D, Ferketich A K and Wooley C F 2005 Volumetric cine CMR to quantify atrial structure and function in patients with atrial dysrhythmias J. Cardiovasc. Magn. Reson. 7 539–43 Sanders P, Morton J B, Kistler P M, Vohra J K, Kalman J M and Sparks P B 2003 Reversal of atrial mechanical dysfunction after cardioversion of atrial fibrillation: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy Circulation 108 1976–84 Schneider C, Malisius R, Krause K, Lampe F, Bahlmann E, Boczor S, Antz M, Ernst S and Kuck K H 2008 Strain rate imaging for functional quantification of the left atrium: atrial deformation predicts the maintenance of sinus rhythm after catheter ablation of atrial fibrillation Eur. Heart J. 29 1397–409 Shen M Y, Liu Y H, Sinusas A J, Fetterman R, Bruni W, Drozhinin O E, Zaret B L and Wackers F J 1999 Quantification of regional myocardial wall thickening on electrocardiogram-gated SPECT imaging J. Nucl. Cardiol. 6 583–95 Slart R H, Bax J J, De Jong R M, De Boer J, Lamb H J, Mook P H, Willemsen A T, Vaalburg W, Van Veldhuisen D J and Jager P L 2004 Comparison of gated PET with MRI for evaluation of left ventricular function in patients with coronary artery disease J. Nucl. Med. 45 176–82 Stefanadis C, Dernellis J and Toutouzas P 2001 A clinical appraisal of left atrial function Eur. Heart J. 22 22–36 Sun J P, Yang Y, Guo R, Wang D, Lee A P, Wang X Y, Lam Y Y, Fang F, Yang X S and Yu C M 2013 Left atrial regional phasic strain, strain rate and velocity by speckle-tracking echocardiography: Normal values and effects of aging in a large group of normal subjects Int. J. Cardiol. 168 3473–9 Thomas L 2007 Assessment of atrial function Heart Lung Circ. 16 234–42 Thomas L, Levett K, Boyd A, Leung D Y, Schiller N B and Ross D L 2003 Changes in regional left atrial function with aging: evaluation by Doppler tissue imaging Eur. J. Echocardiogr. 4 92–100 Wong K K L, Kelso R M, Worthley S G, Sanders P, Mazumdar J and Abbott D 2009 Cardiac flow analysis applied to phase contrast magnetic resonance imaging of the heart Ann. Biomed. Eng. 37 1495–515 Wylie J V Jr, Peters D C, Essebag V, Manning W J, Josephson M E and Hauser T H 2008 Left atrial function and scar after catheter ablation of atrial fibrillation Heart Rhythm. 5 656–62 Zipes D P and Jalife J 2004 Cardiac Electrophysiology: From Cell to Bedside (Philadelphia, PA: Saunders)
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