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DOI: 10.1148/radiol.2433060417
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(Radiology 2007;243:690-695.)
© RSNA, 2007

Cardiac Imaging

Detection of Pulmonary Vein and Left Atrial Scar after Catheter Ablation with Three-dimensional Navigator-gated Delayed Enhancement MR Imaging: Initial Experience1

Dana C. Peters, PhD, John V. Wylie, MD, Thomas H. Hauser, MD, Kraig V. Kissinger, RT, René M. Botnar, PhD2, Vidal Essebag, MD, PhD, Mark E. Josephson, MD, and Warren J. Manning, MD

1 From the Department of Medicine, Cardiovascular Division (D.C.P., J.V.W., T.H.H., K.V.K., R.M.B., V.E., M.E.J., W.J.M.) and Department of Radiology (W.J.M.), Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, RW 453, Boston, MA 02215. Received March 6, 2006; revision requested May 4; revision received June 21; accepted July 20; final version accepted September 27. Supported by grants from the American Heart Association (AHA SDG 0530061N) and the National Institutes of Health (NIBIB K01 EB004434-01A1). V.E. received a Clinician Scientist Award from the Canadian Institutes of Health Research. Address correspondence to D.C.P. (e-mail: dcpeters{at}bidmc.harvard.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Purpose: To prospectively evaluate whether scar caused by radiofrequency (RF) ablation of the left atrium (LA) in patients with atrial fibrillation can be depicted with high-spatial-resolution delayed enhancement magnetic resonance (MR) imaging.

Materials and Methods: All 23 subjects (16 men, seven women; mean age, 54 years ± 13 [standard deviation]) provided written informed consent; the study was approved by the local institutional review board and was HIPAA compliant. A high-spatial-resolution free-breathing delayed enhancement MR imaging method was developed to detect scar (ie, ablated tissue) in the LA and pulmonary veins (PVs). The LA in 15 patients before ablation and in 18 patients at least 30 days after ablation was examined. A reader with 4 years of experience assessed presence of delayed enhancement on images and circumferential completeness. Signal-to-noise and contrast-to-noise ratios were measured and compared with an unpaired t test. The relationship between measurements of enhancement thickness at the interatrial septum and the number of days after ablation was investigated.

Results: No subject demonstrated preablation delayed enhancement of the atrial or PV wall, whereas postablation delayed enhancement was identified in all (100%). In patients after ablation, a partial to completely circumferential delayed enhancement pattern could be identified for the left inferior PV that encompassed 88% ± 11 of the circumference, but only 62% of patients demonstrated more than 90% circumferential delayed enhancement. The signal-to-noise ratio of blood was 12, and the signal-to-noise ratios of the pre- and postablation left atrial wall were 15 and 22, respectively (P < .05). A relationship between delayed enhancement wall thickness and the inverse of the time interval from ablation was identified (P < .05).

Conclusion: High-spatial-resolution delayed enhancement MR imaging allows noninvasive identification of scar induced by RF ablation following isolation therapy of the PV.

© RSNA, 2007


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Radiofrequency (RF) ablation of the left atrium (LA) and the ostium of the pulmonary vein (PV) is an effective treatment (1) and has become accepted as a clinical therapy for atrial fibrillation (AF) that is refractory to antiarrhythmic medications. Reported success rates range from 60% to 85% with the use of diverse electrophysiologic ablation strategies (2–10). Although the goal is electrical PV isolation, anatomic isolation cannot be assessed. Recurrent AF after PV isolation has been associated with loss of electrical isolation of multiple PVs (11). The capability for direct visualization of atrial scar tissue that results from RF ablation would allow further insight into the mechanism of this procedure and a direct comparison of electrophysiologic results with anatomic data.

Furthermore, visualization of scar would permit correlation of RF ablation characteristics with clinical outcomes. The importance of locating these RF ablation sites has been highlighted by researchers in a study (12) in which they demonstrated that intracardiac echocardiography and infusion of microbubbles can aid in the visualization of scar tissue from ablation of the left ventricle in real time.

Delayed enhancement cardiovascular magnetic resonance (MR) imaging helps to identify scar caused by myocardial infarction by displaying the accumulation of gadolinium-based contrast agent in the scarred regions. The scarred regions appear bright (increased signal intensity) (13) on T1-weighted images (14). Findings in studies in animals indicate that there is a close correspondence between such contrast enhancement and irreversible injury in myocardial infarction (15) and RF ablation of the right ventricle (16). In patients, atrial wall imaging poses a greater challenge since the wall of the LA may be fivefold times thinner than the left ventricular myocardium, and, therefore, greater spatial resolution is required. The purpose of our study was to prospectively evaluate whether scar caused by RF ablation of the LA in patients with AF can be depicted with high-spatial-resolution delayed enhancement MR imaging.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Patients
Consecutive patients who were referred for baseline or postablation MR imaging, or both, between April and August of 2005 provided written informed consent and were enrolled in the study. The protocol was approved by the institutional review board of Beth Israel Deaconess Medical Center, Boston, Mass, and the study was Health Insurance Portability and Accountability Act compliant. The 23 study patients included 16 men and seven women, with a mean age of 54 years ± 13 (standard deviation). For 10 patients, two studies were performed, one before and one after ablation, for a total of 20 studies. In five additional patients, only a preablation study was performed, and in eight additional patients, only a postablation study was performed. As a result, 33 MR studies, which included 15 pre- and 18 postablation studies (mean postablation examination time, 92 days ± 134; range, 32–447 days), were performed in 23 subjects. Some patients declined enrollment in either the pre- or postablation study, and others were not referred for either baseline or follow-up MR imaging.

PV Isolation Procedure
Bidirectional PV isolation was performed with an ablation catheter that had an 8-mm nonirrigated tip and a circumferential catheter, placed at each PV ostium to confirm PV entrance and exit block (8), by one electrophysiologist (M.E.J.) who had 5 years of experience in the performance of PV isolation. Catheter manipulation was guided with fluoroscopy, intracardiac ultrasonography, and a three-dimensional electroanatomic mapping system (Carto, Biosense Webster, Diamond Bar, Calif; EnSite NavX, Endocardial Solutions, St Paul, Minn). RF ablation was performed outside each PV ostium at sites with the earliest recorded PV electrograms. Ablation was performed until complete bidirectional electrical isolation of each PV was achieved, and such isolation was defined as entrance block demonstrated with loss of PV potentials and exit block demonstrated with failure to capture the LA by pacing each of the bipolar electrode pairs of the circumferential catheter positioned at the entrance of the PV. None of the patients received additional linear LA ablation lesions. The mean time for actual ablation of the LA with RF power was 3559 seconds ± 1121. Patients were followed up with clinic visits and outpatient ambulatory cardiac monitoring, and recurrent AF was defined as AF on an electrocardiogram or at ambulatory monitoring that was documented more than 30 days after the ablation procedure.

MR Imaging of RF Ablation Sites
MR imaging was performed with a 1.5-T MR imager (Gyroscan ACS-NT; Philips Medical Systems, Best, the Netherlands). During the first pass of a gadopentetate dimeglumine injection (Magnevist; Berlex Laboratories, Wayne, NJ), at a dose of 0.2 mmol per kilogram body weight, PV MR angiography was performed (17). At a mean of 20 minutes ± 5 after injection, three-dimensional delayed enhancement MR imaging of the atria and PVs was performed during free breathing (18,19). For the delayed enhancement MR imaging technique, a three-dimensional inversion-recovery gradient-echo sequence was used for T1 weighting, with one R-R interval between inversion RF pulses. Technical image parameters included the following: repetition time msec/echo time msec, 4.3/2.1; average inversion time, 280 msec; flip angle, 15°; field of view, 30 x 30 x 12.5 cm; full echo; receiver bandwidth, 440 Hz/pixel; matrix, 224 x 224 x 23–32 partition-encoding lines; and voxel size, 1.3 x 1.3 x 5 mm, reconstructed to 0.6 x 0.6 x 2.5 mm. Electrocardiographic gating with an approximately 150-msec end-diastolic window and navigator gating with a 5–7-mm end-diastolic window (20) and no tracking were employed during the 4–8 minutes of total image time. During each acquisition window, data for multiple phase-encoding lines were acquired centrically, for a given constant partition-encoding line (ie, section-encoding line).

When all data for that partition-encoding line had been obtained during multiple heartbeats, the next partition-encoding line was chosen, also in a centric manner. In this way, central partition-encoding data were acquired early in the image period, and central phase-encoding data were acquired early in the data acquisition window. Saturation bands were placed in the phase-encoding (right-left) line to minimize back-folding from the arms; fat saturation was used to suppress signals from fat. For our study, it was important to image with a delay that assured a T1 difference between blood and scar (ie, more than than 15 minutes for a dose of contrast agent of 0.2 mmol/kg) (21,22) to achieve sufficient image contrast. The inversion time to null tissue, TInull, was determined by using a lookup table that provided an inversion time, which was dependent on the time after injection, and an expected myocardial T1, T1myo. By using an estimate of myocardial T1 (23,24) for any time after injection of 0.2 mmol/kg gadopentetate dimeglumine, the appropriate inversion time to null tissue can be estimated by using the following equation: TInull = T1myo · ln(1 + M0) and M0 {approx} 1 – [2 · exp(–RR/T1myo)], where M0 is steady-state longitudinal magnetization prior to the inversion pulse and RR is the R-R interval. For the case in which the R-R interval is much greater than T1, this expression may be simplified to the usual expression TInull = T1myo · ln(2) (23,24). We assumed that T1 of the left atrial wall is similar to myocardial T1.

Data Analysis
The signal intensity values relative to noise (signal-to-noise ratio) in the blood of the LA and in the wall of all PVs were measured. Signals in the thin LA and PV walls were estimated by plotting the signal profile across the walls and averaging two adjacent pixels at the wall location. Blood signal was measured by using an ellipsoid region of interest (approximately 600 pixels) in the left atrium. Noise was measured as the standard deviation of signal in an ellipsoid region of interest (approximately 3000 pixels) placed in the airspace anterior to the chest wall. Contrast-to-noise ratio, CNR, was then measured as CNR = SNRPV wall – SNRblood, where SNRPV wall is the signal-to-noise ratio of the wall of the PV and SNRblood is that of blood. Images from all studies were assessed by a reader (T.H.H.) with 4 years of experience in cardiac MR imaging who was blinded as to whether the study had been performed before or after ablation to determine the presence of left atrial or PV ostial delayed enhancement. The images were obliquely reformatted by using a thin-slab (10-mm-thick) maximum intensity projection technique with the aid of commercial volume-visualization software (EasyVision 5; Philips Medical Systems) to observe the ostia of the PV in cross section and to investigate the anatomy of the scar in this plane.

The reader assessed the circumferential extent, estimated to the nearest 5%, of the left inferior PV ablation for postablation studies by using source images and reformatted images. The left inferior PV was chosen because of the very good quality of scar delineation for this vein. The delayed enhancement (ie, scar) thickness was measured in a blinded fashion across the interatrial septum adjacent to the right superior PV in each patient after ablation to investigate the relationship between scar thickness and the number of days after ablation. For the measurements, we used line profiles across the septum. Although the MR imaging follow-up studies were planned for 30 days after ablation, in our patient cohort, a range of days after ablation was actually used. This range resulted from MR imaging scheduling, imaging performed to rule out suspected stenoses of the PV, and, in one patient imaged more than 1 year after ablation, the planning of a second procedure for isolation of the PV.

Statistical Analysis
Values for continuous variables are reported as the mean ± standard deviation. Values for categoric variables are reported as counts and percentages. The mean signal-to-noise ratio and the mean contrast-to-noise ratio were compared by using an unpaired t test because not all patients were imaged both before and after RF ablation therapy. The discrimination of pre- and postablation images by a blinded observer was assessed by using the Fisher exact test. The relationship between delayed enhancement thickness and the inverse of the number of days from ablation was evaluated by using standard linear regression analysis. A two-sided P value of .05 was used for the determination of statistical significance. All statistical analyses were performed by using software (SAS for Windows, version 9.1; SAS, Cary, NC).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 
Findings on Images
Of the 33 delayed enhancement MR images, six (five of which were obtained after ablation) were uninterpretable because of improper choice of inversion time (n = 3), insufficient injection of contrast agent (n = 1), performance of imaging too early after injection (n = 1), and presence of a wraparound artifact (n = 1). At baseline before ablation, none (0 of 14, 0%) of the remaining preablation delayed enhancement MR images demonstrated atrial wall or PV delayed enhancement; in contrast, all (13 of 13, 100%) (P < .001) of the postablation images demonstrated delayed enhancement of the ostia of the PV or the wall of the LA (Fig 1). The valves and walls of great vessels sometimes appeared enhanced on the delayed enhancement MR images (Fig 1, patient 3) both before and after ablation. In addition, artifactual enhancement of the right PVs was observed on some images because of inflow of signal disturbed by the navigator RF pulse that is placed on the right hemidiaphragm. Enhancement caused by RF ablation was distinguishable from these inflow artifacts because of its location, on the wall of the LA, and because it was not present on preablation images.


Figure 1
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  		Figure 1: Transverse, A, contrast-enhanced MR angiographic images and inversion-recovery gradient-echo, B, preablation and, C, postablation delayed enhancement matched MR images (4.3/2.1; flip angle, 15°; field of view, 30 x 30 x 12.5 cm; voxel size, 1.3 x 1.3 x 5 mm) acquired more than 30 days after ablation in three patients with AF. The MR angiographic image provides anatomic context. Delayed enhancement is not observed before ablation (arrows in B) but is readily observed after ablation (arrows in C). LIPV = left inferior PV, LSPV = left superior PV, RIPV = right inferior PV, RSPV = right superior PV.

 
Delayed enhancement MR images were compared with the electroanatomic map of ablation sites (Fig 2), shown without vein markers, in a patient for whom the left inferior and superior PVs were ablated in common. The reformatted image of the circumferential ablation ring around the left PVs displays the completeness of the ring and also shows common anatomic features (Fig 2). With the study of circumferential ablation patterns, we found that the average circumferential extent of delayed enhancement in the left inferior PV was 88% ± 11. In eight (62%) of 13 patients, the circumferential extent of scar was determined to be more than 90% by using delayed enhancement MR imaging. At follow-up (mean, 149 days ± 72), two (11%) of 18 patients had recurrent AF after ablation. In the two patients with recurrent AF, findings in one study were nondiagnostic, and findings in the other showed an 80% circumferential delayed enhancement for this PV.


Figure 2
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  		Figure 2: Left: Electroanatomic map of the RF ablation sites (red spheres) applied to the common ostium of the left PV in one patient. Color map indicates the measured potentials around the LA before ablation (red = low voltage). Top right: Reformatted 10-mm maximum intensity projection of the three-dimensional delayed enhancement MR image displays the ablation ring of the left PV. Arrows indicate correspondence between the ablation patterns in the two modalities, with less delayed enhancement corresponding to an area of fewer ablation sites (white arrows). Bottom right: Vertical slab indicates sagittal prescription of the reformatted image.

 
Signal-to-Noise and Contrast-to-Noise Ratios
The mean blood pool signal-to-noise ratios were 12 and 11 for pre- and postablation studies, respectively, and the difference between these values was not significant (P = .68). The mean signal-to-noise ratio of the PVs was 15 ± 6 before ablation and 22 ± 6 after ablation, and the difference between them was significant (P = .007). The mean contrast-to-noise ratio was 3 ± 2 before ablation and 11 ± 3 after ablation (P < .001).

There was a significant relationship between the delayed enhancement thickness and the inverse of the number of days from ablation (P = .005) (Fig 3). For four of 13 patients after ablation, the delayed enhancement thickness was not measured either because it was absent in the interatrial septum (n = 2) or because imaging was performed after a second session of RF ablation (n = 2). One patient was imaged at 447 days after ablation, as indicated.


Figure 3
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  		Figure 3: Graph shows scar thinning demonstrated by comparing delayed enhancement (ie, scar) thickness with the inverse of the number of days after the ablation procedure. The relationship between thickness and the inverse of the number of days after ablation was significant (thickness = 1.87 + 43.03[1/d] and P = .005, shown with the regression line).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 References
 
In our study of patients with AF who underwent PV isolation, we found MR imaging evidence of new delayed enhancement (ie, scar) in the LA and ostia of the PV in all subjects after ablation. In addition, a majority (eight of 13) of the postablation ostia of the left inferior PV that we examined demonstrated almost complete (>90%) circumferential delayed enhancement.

After a first RF ablation treatment, 80%–100% of patients with recurrent AF have resumption of electrical conduction into a PV at repeat electrophysiologic study (25–27). Loss of electrical PV isolation has been associated with recurrence of AF (11). Predictors of durability of PV electrical isolation have not been clearly elucidated, however, although research currently is under way (6,9,11). Delayed enhancement MR imaging provides anatomic evidence of the scar created by means of RF ablation and may thereby allow determination of whether scar morphologic characteristics can be used to predict AF recurrence. This imaging provides a new tool for interpretation of clinical results. For patients who develop an AF recurrence, knowledge of the PV anatomic delayed enhancement pattern may also help to guide subsequent ablations. For RF ablation with interventional MR imaging methods to visualize and position the ablation catheter in the LA (16,28,29), this delayed enhancement MR imaging method may allow, in near real time, assessment of the completeness of the lesion.

AF recurrence in the 1st month after a PV isolation procedure may not imply long-term procedural failure (30). Transient inflammatory changes associated with RF ablation and the slow development of scar tissue are thought to be the physiologic correlates of this observation. Our observation that delayed enhancement thickness declines as time after ablation increases may reflect this decrease in inflammation and maturation of scar tissue (10) and is consistent with reports of a decline in delayed enhancement among patients examined early after myocardial infarction and then examined later (15).

There were some limitations to our study. As with all delayed enhancement MR imaging studies, choice of inversion time is critical to image quality, and our method of determining inversion time was based on extrapolations of contrast agent concentration. An image-based approach may be more robust (31), and the phase-sensitive inversion-recovery technique could be adopted (32). Furthermore, the optimum inversion time changes by as much as 20 msec during a 10-minute period (21,22), and this change could contribute to degradation of high-spatial-frequency data. The time between injection of the contrast agent and performance of delayed enhancement MR imaging was not held constant, but this lack of a constant time should not affect results greatly (33).

In this study, evaluation of scar thickness versus time after ablation is limited because the number of patients was small and because the study was an interindividual one. Serial evaluation of individuals is preferred and is currently being investigated. There is no reference standard against which to compare our images of scar from RF ablation in patients. Although half of our subjects displayed an incomplete circumferential delayed enhancement pattern, our initial study was not designed to test the hypothesis that a noncircumferential finding was predictive of the occurrence of AF. A nonplanar ablation pattern may have prevented visualization of circumferential RF ablation scars in some patients. Although an attempt is made during the procedure to achieve circumferential lesions, the end point for RF ablation is bidirectional electrical isolation of the PVs. The small gaps seen on delayed enhancement MR images may represent gaps in the ablation-induced lesions in areas of nonconducting tissue.

Analogous to findings in ischemic heart disease, results of high-spatial-resolution delayed enhancement MR imaging allow noninvasive identification of RF ablation–induced scar following PV isolation therapy. This approach may provide a noninvasive method to evaluate and refine RF ablation therapy. Further studies are necessary to confirm our findings in a larger number of patients and to investigate the relationship between incomplete circumferential delayed enhancement and incomplete PV electrical isolation, and thus recurrent AF.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
References
 


   FOOTNOTES
 

Abbreviations: AF = atrial fibrillation • LA = left atrium • PV = pulmonary vein • RF = radiofrequency

2 Current address: Department of Nuclear Medicine, Technical University of Munich, Munich, Germany. Back

Authors stated no financial relationship to disclose.

Author contributions: Guarantor of integrity of entire study, D.C.P.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, D.C.P., J.V.W., T.H.H., R.M.B., V.E., M.E.J., W.J.M.; clinical studies, all authors; statistical analysis, D.C.P., T.H.H., W.J.M.; and manuscript editing, all authors


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 References
 

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