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Am J Physiol Heart Circ Physiol 294: H1002-H1009, 2008. First published December 14, 2007; doi:10.1152/ajpheart.01297.2006
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Integrated multimodal-catheter imaging unveils principal relationships among ventricular electrical activity, anatomy, and function

Liyun Rao,1 Yuesheng Ling,1 Renjie He,2 April L. Gilbert,1 Nikolaos G. Frangogiannis,3 Jianwen Wang,1 Sherif F. Nagueh,1 and Dirar S. Khoury1

1Department of Cardiology, Methodist DeBakey Heart Center, The Methodist Hospital Research Institute; 2Department of Diagnostic and Interventional Imaging, Health Science Center, University of Texas; and 3Section of Cardiovascular Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas

Submitted 28 November 2006 ; accepted in final form 11 December 2007


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Multiple imaging modalities are employed independent of one another while managing complex cardiac arrhythmias. To combine electrical, anatomical, and functional imaging in a single catheter system, we developed a balloon catheter that carried 64 electrodes on its surface and an intracardiac echocardiography (ICE) catheter through a central lumen. The catheter system was inserted, and the balloon was inflated inside the left ventricle (LV) of eight dogs with 6-wk-old infarction, created by occlusion in the left anterior descending coronary artery. Anatomy was constructed by ICE imaging (9 MHz) through the balloon. Single-beat noncontact mapping (NCM) was performed via the multielectrode array to reconstruct unipolar endocardial electrograms during sinus rhythm. Standard contact mapping (CM) of the endocardium was also carried out for reference. Myocardial infarction in anterior LV extending from the middle to apical regions was localized both by ICE and NCM and validated by CM and pathology. The overall difference in the activation times between NCM and CM was 3 ± 1 ms. Unipolar voltage in infarcted middle anterior LV was smaller than the voltage in normal middle inferior LV both by NCM (11 ± 4 vs. 16 ± 3 mV; P = 0.002) and CM (11 ± 3 vs. 20 ± 4 mV; P < 0.001). Unipolar voltage was also inversely related to infarct transmurality, both by NCM (r = –0.87; P = 0.005) and CM (r = –0.94; P < 0.001). The infarct area by ICE (7.7 ± 2.9 cm2) was in agreement with CM (bipolar voltage, <1 mV; and area, 7.6 ± 3.3 cm2; r = 0.80; P = 0.016). Meanwhile, the voltage threshold that depicted the infarct area by NCM was directly related to the smallest unipolar voltage reconstructed within the infarct (r = 0.96; P < 0.001). In conclusion, combining NCM and ICE imaging in a single catheter system is feasible. The preclinical development of such an integrated system and its evaluation in experimental myocardial infarction demonstrate capabilities for single-beat mapping at multiple sites as well as the online assessment of anatomy and myocardial function.

electrophysiology; myocardial infarction; noncontact mapping

THE ONLINE VISUALIZATION of endocardial structures during electrophysiology procedures can advance the understanding of complex cardiac arrhythmias in relation to the underlying anatomy and may improve their management. However, present endocardial mapping systems (6, 11, 18, 29) do not currently provide capabilities for true online anatomical imaging. To address this limitation, recent studies have focused on importing into the catheterization laboratory anatomic images of the heart acquired in advance using computed tomography or magnetic resonance imaging and combining the cardiac anatomic images with electrical mapping (7, 17, 25). Challenges inherent in this approach include anatomic variability due to image acquisition at different time points and subsequent accurate image registration and fusion. More importantly, although this approach could be valuable in providing a road map for managing complex arrhythmias such as atrial fibrillation triggered by pulmonary vein foci, it neither permits the online assessment of anatomical or functional variations before, during, or after the delivery of therapy, nor does it enable verifying electrode-catheter contact with specific endocardial structures. Multiple imaging modalities are presently employed independent of one another in ways that do not allow an efficient diagnosis or comprehensive evaluation of therapy (1, 20, 26).

Combining online anatomical and functional imaging with endocardial mapping during catheterization can address some of the challenges described above and may provide several advantages. Our objective was to develop a method that integrates two previously established imaging modalities into a single catheter system by using 1) noncontact endocardial mapping, which has proved to be valuable for single-beat three-dimensional electrical imaging (15, 24) and 2) intracardiac echocardiography (ICE), which has provided considerable advantages for online guidance during electrophysiology procedures by imaging true detailed anatomical structures (16, 23). In this study, we validated the combined imaging approach on the basis of a clinically relevant condition represented by a canine myocardial infarction model.


   METHODS
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 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
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Animal preparation. The study protocol was approved by the Animal Care and Use Committee of the Institute of Biosciences and Technology at Texas A & M University. The protocol adhered to the Public Health Service guidelines for the Care and Use of Laboratory Animals. Ten adult mongrel dogs (weight, 35–40 kg) were studied. Before any experimental operation, each dog was preanesthetized by an intramuscular injection of xylazine (0.75–1.5 mg/kg) and atropine (0.02–0.06 mg/kg), anesthetized by an intravenous injection of propofol (5 mg/kg), and continued on isoflurane inhalation (2–3%) for the remainder of the study. Continuous intravenous saline infusion and the monitoring of ECG, oxygen saturation, and body temperature were maintained. Each dog underwent two procedures, wherein percutaneous catheterization was carried out to measure left ventricular (LV) pressure (5-Fr, SPC-350; Millar Instruments) and transthoracic echocardiography (Vivid 7; GE Healthcare) was performed to assess LV volume and function.

An initial procedure was performed whereby the heart was exposed through a left lateral thoracotomy and a small incision was made through the pericardium. The left anterior descending coronary artery (LAD) was dissected from the surrounding tissue between the first and second diagonal branches, and a snare was placed on the isolated LAD. Lidocaine hydrochloride (2 mg/kg) was administered intravenously, followed by partial LAD occlusion for 20 min and a complete occlusion thereafter. Epinephrine, dobutamine, and lidocaine were administered as needed to counteract adverse acute electrophysiological changes during occlusion. A rest period of 1 h was allowed, after which the chest was closed and the dog was allowed to recover. Treatment with antibiotics and analgesics was followed postsurgery.

A second procedure was conducted 6 wk post-LAD occlusion. Standard percutaneous contact electroanatomic mapping of the LV endocardium was performed during sinus rhythm using a 7-Fr, 4-mm tip quadripolar electrode catheter (Carto; Biosense Webster and Johnson and Johnson). Unipolar electrograms were recorded from the tip electrode with the Wilson central terminal as a reference (filtered at 0.05–400 Hz), whereas bipolar electrograms were recorded between the tip electrode and a closely spaced (1 mm) ring electrode (filtered at 30–400 Hz), all at a sampling interval of 1 ms. Subsequently, the heart was exposed through a median sternotomy and suspended in a pericardial cradle. Noncontact multimodal catheter imaging of the LV was then employed as described in Noncontact catheter imaging system.

Noncontact catheter imaging system. As shown in Fig. 1A, we built a custom noncontact catheter system on the basis of a balloon catheter that contained a 9-Fr central lumen. The balloon (length = 40 mm and maximum diameter = 15 mm; NuMed) carried on its surface an expandable multielectrode array that consisted of 64 electrodes arranged in 8 columns with 8 electrodes/column (interelectrode spacing = 4 mm). The lumen permitted inserting a standard ICE catheter (9-Fr, 9 MHz, Ultra ICE; Boston Scientific) that continuously recorded anatomical images through the balloon.


Figure 1
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  		Fig. 1. A: integrated imaging system consisting of a balloon catheter carrying a multielectrode array over its surface and an intracardiac echocardiography (ICE) catheter through a central lumen. B: radiograph depicting the catheter system in the canine left ventricle (LV) and showing the tip of the ICE catheter beyond the inflated balloon. C: radiograph illustrating the ICE catheter inside the lumen while imaging through the inflated balloon. RA, right atrium; RV, right ventricle.

 
Noncontact electrical, anatomical, and functional imaging. The noncontact catheter system was a preclinical version and not yet suited for a percutaneous insertion in the LV. Therefore, with the balloon collapsed and the ICE catheter inside the lumen, the combined catheter system was surgically inserted into the LV through the apex. The balloon was placed along the LV major axis under the guidance of both fluoroscopy and ICE and then inflated with 2.5 ml saline to expand the multielectrode array as shown in Fig. 1 and effectively create a noncontact mapping multielectrode probe.

Noncontact unipolar electrograms sensed by the multielectrode probe were filtered between 0.05–500 Hz and, along with body surface ECG, were acquired simultaneously with a multichannel recording system (CardioLab; GE Healthcare) that amplified and sampled the signals at 1-ms intervals. The Wilson central terminal was used as a reference for unipolar electrograms.

To display detailed anatomy, multiple continuous two-dimensional images were acquired by ICE, starting with the tip at the LV base beyond the distal end of the balloon, and by pulling the ICE catheter back in 2-mm increments through the lumen, ending at the apex as illustrated in Fig. 1, B and C. The ICE images were viewed on an imaging console (ClearView; Boston Scientific) and recorded at a sampling rate of 30 frames/s, along with the body surface ECG. A predefined marker, placed on the shaft of the balloon catheter along one of the columns of electrodes, was distinctly depicted during ICE imaging from inside the lumen. The marker projected onto the ICE image and served as a reference point for aligning and orienting the electrode array during ICE imaging. The ICE catheter pullback was assumed to follow a straight path within the balloon. Accordingly, the fixed shape of the balloon catheter and the geometry of the cavity were described in one coordinate system. Additional radiopaque and sonopaque ring markers confirmed the alignment.

Pathological evaluation. At the end of the study, the animal was euthanized by a rapid intravenous injection of KCl (30 meq). Subsequently, the heart was removed from the chest and sectioned into three transverse rings. Seventeen myocardial segments, consisting of six segments at both basal and midventricular levels and five segments at the apex, were obtained following the American Heart Association recommendations on standardized myocardial segmentation for tomographic imaging of the heart (5). The samples were fixed in B-5 without Formalin (3) and embedded in paraffin. Sequential 3–5-µm sections were cut by microtomy. The sections were stained with hematoxylin-eosin and picrosirius red staining as previously described (19). Slides were examined under a microscope (Zeiss). The infarcted myocardium was identified as the area of collagen-based scar. The area of infarction was assessed for the subendocardial and subepicardial half of each segment and expressed as a percentage of the total myocardial area (percent infarct transmurality).

Data analysis. ICE images acquired at multiple pullback levels and over several beats were synchronized. A semiautomatic method was employed in segmenting the endocardium at each level, whereby a custom algorithm automatically detected and digitized the boundary between manually placed marks. The endocardial boundary was extracted at end diastole (peak QRS on surface ECG) (8, 21), the same time instant during the cardiac cycle at which the Carto geometry was acquired. Total LV volume was computed by integrating multiple cross-sectional areas along the major axis of the cavity (using Simpson rule). Two investigators independently identified the myocardial region exhibiting abnormal wall motion (akinesis or dyskinesis) or scar on ICE and manually segmented the corresponding endocardial boundary at each pullback level. The infarct area by ICE was computed using a numeric surface integration of the segmented endocardium, and the average area in each dog was then determined.

Similar to previous work of our laboratory (14, 15), electrograms were numerically reconstructed (by employing the inverse solution) at an average of 1,973 points on the LV endocardial surface on the basis of noncontact electrograms measured by the mutlielectrode cavitary probe and three-dimensional geometry derived by ICE. Electroanatomic maps by Carto were constructed on the basis of >200 sequential contact points on the endocardium in each dog. The moment of the minimum first derivative defined the activation time of endocardial unipolar electrograms obtained both by contact and noncontact mapping. Endocardial unipolar electrogram duration was defined as the interval between electrogram onset (beginning of Q wave) and the activation time. All time intervals were corrected for heart rate to account for the variation between contact and noncontact mapping. The magnitude of contact endocardial bipolar electrogram voltage was measured as the absolute difference between the maximum voltage and the minimum voltage. The infarct area by Carto was determined following standard bipolar voltage mapping employing a fixed voltage threshold of 1 mV (4, 10). The magnitude of contact and noncontact endocardial unipolar electrogram voltage was determined as the absolute difference between the maximum voltage (during QR interval) and the minimum voltage (during RS interval).

The analysis of the LV was based on a 16-segment model that excluded the apical cap. Comparisons between contact and noncontact mapping data were not made at exactly the same endocardial locations but rather within the vicinity of one another in the middle of each of the 16 segments in each dog. Contact electrogram parameters were averaged over three sites in each segment. Data were compared using a paired t-test and are presented as means ± SD. Correlations were analyzed using simple linear regression. A P value of <0.05 was considered statistically significant, and n represents the number of dogs.


   RESULTS
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 METHODS
 RESULTS
DISCUSSION
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Animal model. Eight out of 10 dogs survived for a period of 6 wk after LAD occlusion and successfully underwent a second procedure for electrophysiological evaluation. One dog died a day after LAD occlusion, and the other died 2 wk following LAD occlusion. At 6 wk, transthoracic echocardiography consistently depicted abnormal wall motion in anterior LV with variable extent from the middle to apical regions. All surviving dogs were stable with minor changes on average in LV hemodynamics (baseline vs. infarct: QRS duration, 76 ± 6 vs. 78 ± 9 ms; ejection fraction, 39 ± 5 vs. 36 ± 7%; end-systolic pressure, 107 ± 8 vs. 104 ± 16 mmHg; and end-diastolic pressure, 18 ± 3 vs. 17 ± 3 mmHg).

ICE imaging of myocardial infarction. ICE imaging from the center of an inflated balloon catheter was feasible and enabled the online visualization of important details of underlying anatomy as illustrated in Fig. 2. Using ICE, we identified the orientation of the LV walls and observed the aortic and mitral valves, papillary muscles, interventricular septum, and right ventricle. There was no significant change in stroke volume before (22 ± 5 ml) and after (22 ± 8 ml) inserting and inflating the balloon catheter as determined in the LV by epicardial echocardiography (n = 5). The LV end-diastolic volume determined by ICE (76 ± 10 ml) and the corresponding volume determined by contact electroanatomic mapping (79 ± 15 ml) were in excellent agreement (r =0.95; n = 8; P < 0.001). The analysis of continuous ICE images recorded 6 wk after LAD occlusion confirmed the loss of contractile function, reduction in myocardial systolic thickening, and/or scar formation in anterior LV between the middle and apical regions. The infarct area by ICE (mean, 7.7 ± 2.9 cm2; and range, 3.1–10.9 cm2) was in good agreement with the infarct area (defined as voltage < 1 mV) by standard contact bipolar voltage mapping (mean, 7.6 ± 3.3 cm2; and range, 2.6–12.6 cm2; r = 0.80; P = 0.016; n = 8).


Figure 2
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  		Fig. 2. ICE images acquired from inside the lumen and through the multielectrode balloon. A: basal LV. B: middle LV. C: apical LV. Distinct shadows in the ICE images were caused by the mapping electrodes on the balloon. Yellow arrowheads point to infarct region. D: quantitative assessment of the extent of myocardial infarction was performed using picrosirius red staining (top) to label the collagen fibers in the healing infarct. A serial section (bottom), stained with hematoxylin-eosin, demonstrates the corresponding area of cardiomyocyte replacement with scar. Arrows identify border zone between infarcted and noninfarcted myocardium (original magnification, x12.5). E: photograph of gross pathology of middle LV segment corresponding to the ICE image in B. F: photograph of gross pathology of apical LV segment corresponding to the ICE image in C. AP, anterior papillary muscle; PP, posterior papillary muscle.

 
Noncontact endocardial activation mapping of myocardial infarction. Single-beat endocardial electrograms reconstructed by noncontact mapping during sinus rhythm yielded a highly accurate estimation of endocardial activation times and corresponding sequences compared with contact electroanatomic mapping. As summarized in Fig. 3, the difference in activation times between noncontact and contact mapping at 16 LV segments in all eight dogs was 3 ± 1 ms (range, 2–6 ms), and the activation sequences through 16 LV segments were well correlated between the two mapping methods (mean, r = 0.89 ± 0.05; and range, r = 0.81–0.96; n = 8).


Figure 3
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  		Fig. 3. Circumferential polar plots of 16 LV myocardial segments summarizing electrical-mapping results from 8 dogs. Top row: activation times and unipolar voltages determined in the middle of each LV segment by noncontact mapping during sinus rhythm. Bottom row: activation times, bipolar voltages, and unipolar voltages determined in the middle of each LV segment by contact electroanatomic (Carto) mapping during sinus rhythm. A, anterior; AL, anterior lateral; AS, anterior septum; I, inferior; IL, inferior lateral; IS, inferior septum.

 
During sinus rhythm, noncontact mapping depicted the earliest LV activation in the midseptum (Fig. 4). Septal activation rapidly expanded in basal and apical directions and was followed by the spread of activation toward anterior and inferior LV. However, the activation of anterior LV between the middle and apical regions exhibited conduction block and was significantly delayed compared with the activation of inferior LV (middle anterior LV, 23 ± 5 ms from onset of activation; and middle inferior LV, 11 ± 4 ms from onset of activation; P = 0.004). Unipolar electrograms reconstructed in the infarct region frequently exhibited more than one phase, which were in agreement with corresponding unipolar electrograms recorded by contact mapping. The last part to activate on the LV endocardium was generally in the anterior lateral region.


Figure 4
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  		Fig. 4. Top, left: map of LV activation sequence derived by contact endocardial electroanatomic mapping (Carto) at multiple sequential points. Top, right: map of LV activation sequence reconstructed in the same dog by noncontact endocardial mapping of a single heartbeat. Both maps are shown during sinus rhythm, with the red color representing area of earliest activation initiating from the septum. Representative endocardial unipolar electrograms along with surface ECG (lead II) are shown. Each group of signals is displayed at the same scale, with a calibration pulse indicated in the corresponding row. Bottom, left: standard voltage map depicting amplitudes of LV endocardial bipolar electrograms recorded by contact electroanatomic mapping. Bottom, right: voltage map depicting amplitudes of LV endocardial unipolar electrograms reconstructed in the same dog by noncontact mapping. Both maps are shown during sinus rhythm, with the red color portraying area of low voltage in anterior LV reflecting underlying infarct. Bottom left inset: a schematic of the heart with orientation approximated by Carto. Bottom, right, inset: actual orientation of the right ventricular cavity in relation to the LV cavity as determined by simultaneous ICE imaging. All maps are displayed in anteroposterior view. Maps shown are from the same dog in Fig. 2.

 
Noncontact endocardial voltage mapping of myocardial infarction. Unipolar electrograms in the infracted middle anterior LV region were significantly smaller in amplitude than electrograms in the normal middle inferior LV region both by noncontact mapping (11 ± 4 vs. 16 ± 3 mV; P = 0.002) and contact mapping (11 ± 3 vs. 20 ± 4 mV; P < 0.001). The difference in the amplitude of endocardial unipolar electrograms by noncontact and contact mapping at 16 LV segments in all eight dogs was 18 ± 6% (range, 11–26%) as summarized in Fig. 3. There was an inverse relationship between the magnitude of unipolar voltage and the endocardial-to-epicardial transmural extent of the infarct in middle anterior LV (Fig. 5), as determined both by noncontact mapping (r = –0.87; n = 8; P = 0.005) as well as by contact mapping (r = –0.94; n = 8; P < 0.001). Contact bipolar electrograms in middle anterior LV were significantly smaller than electrograms in middle inferior LV (0.8 ± 0.2 vs. 3.9 ± 1 mV; P = 0.001). However, bipolar electrogram voltage did not correlate with infarct transmurality (r = –0.50; n = 8; P = not significant). Endocardial unipolar electrogram duration in middle anterior LV was significantly longer than electrogram duration in middle inferior LV both by noncontact mapping (35 ± 4 vs. 19 ± 7 ms; P < 0.001) and contact mapping (28 ± 2 vs. 12 ± 4 ms; P < 0.001). There was no apparent relationship between unipolar electrogram duration and infarct transmurality.


Figure 5
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  		Fig. 5. Linear regression analysis of infarct endocardial-to-epicardial transmurality in middle anterior LV and corresponding unipolar electrogram amplitude as determined by noncontact mapping (top) and contact electroanatomic mapping (bottom).

 
The infarct region delineated by noncontact unipolar-voltage mapping was comparable with the region identified by contact bipolar voltage mapping (Fig. 4). However, the unipolar voltage threshold, achieving infarct areas by noncontact mapping similar to contact bipolar voltage mapping, varied among dogs (mean, 12.1 ± 4.8 mV; and range, 7.0–22.0 mV). The voltage threshold resulting in optimal infarct area by noncontact mapping was directly related to the smallest endocardial unipolar voltage reconstructed by noncontact mapping within the infarct region (y = 2.0 + 1.1x; r = 0.96; n = 8; P < 0.001) and inversely related to the average infarct transmurality (y = 21.8–0.2x; r = –0.79; n = 8; P = 0.019).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
To better understand cardiac electrophysiological properties in relation to underlying anatomy, multiple noninvasive as well as catheter-based imaging techniques are presently employed before, during, or after catheterization that are, however, performed independent of one another. The present study described a novel approach for combined LV electrical, anatomical, and functional imaging by introducing a catheter system that efficiently integrated noncontact endocardial mapping and echocardiographic imaging. Some of the advantages of a preclinical form of an integrated catheter imaging system were demonstrated in a canine model of chronic myocardial infarction. The study showed that the innovative operation of ICE in the center of a cavitary balloon carrying an electrode array on its surface enabled the online visualization of LV anatomy and myocardial function and allowed the reconstruction of three-dimensional geometry. Accordingly, endocardial electrograms reconstructed on the basis of single-beat noncontact electrograms measured by a cavitary multielectrode probe and geometry derived from ICE yielded an accurate depiction of endocardial activation sequence and voltage pattern, reflecting the location, extent, and transmurality of myocardial infarction.

We previously established the accuracy of using ICE in measuring LV volumes by comparison with the standard thermodilution method (8). In the present study, ICE imaging included an acquisition from inside a balloon catheter. The accuracy of using ICE was confirmed by the excellent agreement between end-diastolic volume reconstructed by ICE and the corresponding volume determined by standard contact electroanatomic mapping (Carto), a system that has been repeatedly validated.

The precision of ICE in recovering three-dimensional endocardial anatomy and multielectrode probe location inside the cavity is an important factor impacting the accuracy of endocardial potentials and the corresponding activation obtained by the inverse solution. When compared with previous work (14, 15), the present study confirmed that ICE imaging further improved the accuracy of reconstructed endocardial activation derived by noncontact mapping. Furthermore, the amplitudes of reconstructed electrograms were in reasonable agreement with the amplitudes of contact unipolar electrograms measured at corresponding LV segments. Causes of variability include differences in the sites within the same myocardial segment at which contact and noncontact electrograms were compared, the electrode size used in contact recording, and inherent uncertainty in electroanatomic mapping regarding the degree of electrode contact and its orientation with the endocardium.

The amplitude of the endocardial unipolar electrogram derived by noncontact mapping was inversely related to infarct transmurality. This novel finding could be useful in quantifying surviving myocardium in the infarct region. Endocardial unipolar electrograms independently measured by contact electroanatomic mapping further confirmed the amplitude dependence on infarct transmurality. Meanwhile, the amplitude of the endocardial bipolar electrogram measured by contact electroanatomic mapping did not have a significant relationship with infarct transmurality in the present study, a result that is probably impacted by the small sample size given the narrow range of bipolar voltage in the infarct region and considering the factors altering the morphology of recorded bipolar signals (15a). These findings are in line with the common knowledge of unipolar electrograms reflecting more far-field potentials than bipolar electrograms. Variable results were obtained in previous studies on changes in bipolar electrograms with respect to infarct thickness (10, 30).

Reentrant ventricular tachycardia circuits are often associated with infarcted myocardium. Contact endocardial bipolar electrogram voltage has been repeatedly shown to accurately reflect infarct area with a widely used voltage threshold value of 1 mV (4, 10). The ability of bipolar voltage to clearly distinguish infarct-diminished local electrical activity from neighboring regions can be observed in Fig. 3. It has been difficult to accurately determine infarct area by contact unipolar voltage mapping employing a fixed voltage cutoff value (4, 10). Similarly, with the use of a commercial noncontact mapping system, early studies showed that determining infarct area by noncontact unipolar voltage mapping was not reliable when a fixed voltage threshold was attempted (22, 28). More recent studies have attempted to delineate the infarct area by noncontact mapping on the basis of different electrogram characteristics (27) or additional pacing maneuvers in the infarct region (12) with variable results. Studies thus far have focused on determining a voltage threshold in relation to the maximum voltage reconstructed by noncontact mapping. However, the present study clearly demonstrated that the voltage threshold, yielding an infarct area that matched well with contact bipolar voltage mapping, was variable and highly correlated with the minimum voltage reconstructed by noncontact mapping within the infarct region. This relationship appeared to be influenced by varying infarct transmurality among different dogs.

Infarction was provoked as a pathologically relevant condition that enabled validation of the different components of the catheter imaging system. ICE enabled true dynamic imaging and identified reduced systolic thickening and wall-motion abnormality in the middle to apical aspects of anterior LV. The presence of multiple infarcts in different regions, as is often the case in humans, could be a challenge for noncontact voltage mapping alone to depict. However, combining noncontact mapping and ICE imaging together could be useful in evaluating LV infarcts during catheterization.

The catheter system employed in the study is a prototype preclinical version (outer diameter, 15-Fr) and requires additional refinement to reduce its size for safe-routine percutaneous insertion and placement inside the heart. This can be accomplished by better assembly and selecting smaller components. The size limitation notwithstanding, we are presently able in ongoing canine studies to percutaneously insert the catheter system through the jugular vein and perform imaging inside the right atrium.

Although imaging by ICE was performed over several heartbeats, imaging through a balloon carrying multiple sensors is a novel approach that rendered valuable online information not readily available from other present mapping systems. This approach may be expanded to include imaging catheters utilizing alternate ultrasound modalities such as ones based on multiple phased-array ultrasound transducers (9). Although the study aim was not to compare the quality of images acquired with different commercial ICE catheters, imaging with a phased-array system operating at a lower ultrasound frequency may allow deeper sound wave penetration inside the myocardium, which ensures more distinct echocardiographs. The recent addition of a position sensor in the shaft of such an ultrasound imaging catheter will make it possible to use the catheter in future studies for reconstructing three-dimensional geometry. In the meantime, multimodal noncontact imaging was satisfactorily accomplished in the present study using a rotational-transducer ICE catheter along the fixed axis of a balloon catheter without the necessity for a position sensor.

Several experimental factors could account for the differences between the results of contact and noncontact mapping. The procedures were performed in sequence with the former performed in the closed-chest state and the latter in the open-chest state. A prolonged period of anesthesia and surgical instrumentation of the heart at the time of noncontact mapping might have impacted electrical activation, myocardial function, and hemodynamics. Although contact mapping depended on catheter electrode size, direction, the degree of contact, and the number of sampling points at the endocardium, noncontact endocardial electrogram morphology and the corresponding activation sequence were possibly variably impacted by the smoothness imposed by numeric regularization while solving the inverse problem.

The ejection fraction appeared somewhat diminished at the normal baseline state, most likely due to the anesthetic agents administered before and during the procedure. The decrease in ejection fraction in the setting of myocardial infarction compared with baseline was not significant, presumably due to the relatively small size of the infarct and to the apparent enhancement in inferior wall function compared with baseline as delineated by transthoracic echocardiography.

The present study is a primary step in the systematic validation of the different components of a novel noncontact multimodal-imaging catheter in the setting of myocardial infarction. The inducibility and mapping of ventricular tachycardia associated with this disease model merit further investigation. Insofar as anatomical imaging is performed over several heartbeats, we speculate that localizing myocardial infarction during sinus rhythm by noncontact voltage mapping as well as by ICE may compensate for the possible inaccuracy associated with error in geometry during rapid tachycardia. This limitation notwithstanding, the catheter system may have several clinical implications such as reduced dependence on fluoroscopy during catheterization, enhanced understanding of cardiac arrhythmias in relation to underlying anatomy, better navigation and positioning of diagnostic or therapeutic electrode catheters, and improved delivery and assessment of pharmacological or electrical interventions.

Conclusions. Combining noncontact mapping and ICE imaging in a single catheter system is feasible. The preclinical development of such an integrated system and its evaluation in experimental myocardial infarction demonstrate capabilities for single-beat electrical mapping at multiple sites as well as the online assessment of anatomy and myocardial function.


   GRANTS
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This work was supported by National Heart, Lung, and Blood Institute Grants R01-HL-68768 (to D. S. Khoury) and R01-HL-76246 (to N. G. Frangogiannis).


   FOOTNOTES
 

Address for reprint requests and other correspondence: D. S. Khoury, The Methodist Hospital Research Inst., 6565 Fannin St., F764, Houston, TX 77030 (e-mail: dkhoury{at}tmhs.org)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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