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Fusion of imaging technologies: how, when, and for whom?

Ashul Govil & Hugh Calkins & David D. Spragg

Received: 3 November 2010 /Accepted: 14 August 2011 /Published online: 1 October 2011# Springer Science+Business Media, LLC 2011

Abstract Over the past decade, electroanatomic mapping

has emerged as a useful tool for complex ablation

procedures. A more recent advancement is the development

of image integration. Image integration refers to the processof registering a previously acquired MRI or CT scan of the

heart with the mapping space during the ablation procedure.

The technique of image integration is now relied on by

many electrophysiology laboratories to guide complex

ablation procedures, particularly atrial fibrillation ablation

and ablation of patients with ventricular tachycardia in the

setting of structural heart disease. An even more recent

development is image fusion. This refers to taking

information about the myocardial substrate, especially

intramyocardial scar, and registering it with the active

mapping space. This technique remains in its infancy but

shows great promise in facilitating complex ablation

procedures. The purpose of the article is to review the

development, state of the art, and future of these image

integration and fusion techniques.

Keywords Imaging technologies . Fusion . Image

integration . Ablation . Mapping

1 Introduction

During the past 20 years, tremendous advances have been

made in the tools used to perform ablation procedures.

When radiofrequency ablation was discovered to be a safe and

effective therapy for many types of cardiac arrhythmias two

decades ago, ablation procedures were guided by fluoroscopic

imaging as well as intracardiac electrograms. Mapping wasused to identify the earliest site of atrial or ventricular

activation, the presence of discrete electrical signals such as

accessory pathway potentials, mid-diastolic potentials, or the

His bundle, or evidence of a slow zone of conduction critical

for reentrant arrhythmias such as ventricular tachycardia and

atrial flutter. Although these mapping tools proved to be more

than adequate for guiding catheter ablation of accessory

pathways , atrioventricular nodal reentran t tachycardia

(AVNRT), atrial flutter, and idiopathic ventricular tachycar-

dia arising in the right ventricular outflow tract, they were far

less helpful in guiding ablation of complex arrhythmias.

Today, the field of catheter ablation has changed dramatically.

Whereas ablation of accessory pathways and AVNRT kept

electrophysiologists fully occupied 20 years ago, the focus has

shifted to catheter ablation of more complex arrhythmias

including atrial fibrillation, complex atrial tachycardias, and

ventricular tachycardia. The great progress made in ablating

these more challenging arrhythmias can be attributed, in a

large part, to the development and perfection of three-

dimensional (3-D) mapping systems. These currently include

the Biosense Webster Carto system and the St. Jude Medical

NavX system. Even more recently, it has become possible to

take advantage of the detailed anatomic information provid-

ed by intracardiac echocardiogram, CT, and MRI scans of the

heart through the use of image integration. The purpose of

this article is to provide a state-of-the art review of image

integration today and also to look toward the future.

2 Three-dimensional mapping systems

There currently are two main 3-D mapping systems which

are in wide spread clinical use in the USA. Although both

A. Govil

Department of Medicine, Johns Hopkins Bayview Medical Center,

Baltimore, MD, USA

H. Calkins : D. D. Spragg (*)

Division of Cardiology, The Johns Hopkins Hospital,

600 N. Wolfe Street, Carnegie 568,

Baltimore, MD 21287, USA

e-mail: [email protected]

J Interv Card Electrophysiol (2011) 32:195 – 203

DOI 10.1007/s10840-011-9616-7



of these systems are capable of accurately localizing a

mapping site or ablation point in three-dimensional space,

the technologies used to accomplish this differ, as do some

important ancillary features.

The first three-dimensional mapping system to be

developed was the Biosense Webster Carto XP system.

The CARTO system uses magnetic technology to accurate-

ly determine the location and orientation of the mapping/ ablation catheter and simultaneously records the local

electrogram from its tip. Sampling a sufficient number of

endocardial sites allows for reconstruction of the three-

dimensional geometry of the chamber, with the electro-

physiological information color-coded and superimposed

on the anatomy (Fig. 1). The system has been shown to be

highly accurate in both in vitro and in vivo studies [1]. The

mapping and navigation system is comprised of a miniature

passive magnetic field sensor, an external ultra-low mag-

netic field emitter (location pad), and a processing unit

(CARTO, Biosense). The locatable catheter is similar to a

regular electrophysiological 8F deflectable-tip catheter. Thecatheter tip is mounted on the distal end of the shaft and

includes the tip electrode and several additional proximal

electrodes that enable recording of unipolar or bipolar

signals. Just proximal to the tip electrode lies the location

sensor, totally embedded within the catheter. Signals

received within the sensor are transmitted along the catheter

shaft to the main processing unit. The locator pad is located

beneath the operating table and generates ultra-low mag-

netic fields (5×10−6 to 5×10−5 T) that code the mapping

space around the patient's chest with both temporal and

spatial distinguishing characteristics. These fields contain

the information necessary to resolve the location and

orientation of the sensor in six degrees of freedom ( x, y, z ,

roll, pitch, and yaw). The locator pad includes three coils.

Each coil generates a magnetic field that decays as a

function of the distance from that coil. The sensor measuresthe strength of the magnetic field, thus enabling determi-

nation of the distance from each of its sources. These

distances determine the radii of theoretical spheres around

each coil. The intersection of these three spheres determines

the location of the sensor in space. The location of the

mapping catheter is gated to a fiducial point in the cardiac

cycle and recorded relative to the location of the fixed

reference catheter at that time.

A second three-dimensional mapping system that is

currently available clinically is the NavX system (Endocar-

dial Solutions Inc., St. Paul, MN, USA) [2, 3]. This system

utilizes regular mapping and ablation catheters to sense a 5.6-kHz, low-current electrical field generated in the thorax

by externally placed electrodes. It has the ability to generate

an anatomic map and superimpose the locations of up to 64

catheter electrodes upon the map. A three-dimensional

computer model of the left atrium (LA) can be created by

dragging the ablation or multipolar catheter on the

endocardial surface and in each of the pulmonary veins

(PVs; Fig. 2). This nonfluoroscopic navigation system can

LAO Lateral

Fig. 1 CARTO mapping of the left ventricle, showing left anterior

oblique ( LAO) and lateral projections. The voltage maps demonstrate

a large inferior region of scar extending from the mitral valve ( white

ring ) to the ventricular apex. Dense scar is shown in grey, diseased

peri-infarct tissue is shown in red , and normal tissue in purple

196 J Interv Card Electrophysiol (2011) 32:195 – 203



display anatomic structures in three dimensions, includingthe precise location of PV ostia, as well as the relative

position of catheters and the sites of radiofrequency

application.

More recently, there has been the development of the

CARTO 3 system that improves on the original CARTO

system. CARTO 3 was recently released and makes

several improvements on the original system. Like the

original CARTO system, CARTO 3 uses magnet-based

localization for visualization of the catheter and map-

ping, but the new system incorporates nine magnets

within the locator pad as opposed to the original six

that may allow for greater accuracy and compensation

for patient movement. Unlike the original CARTO

system, CARTO 3 also allows for non-gated mapping

of the catheter. In addition, the new system merges the

magnet-based system with a new impedance-based

technology. The merging of magnetic- and impedance-

based technologies along with non-gated timing allows

for both tip and catheter curve visualizations as well as

simultaneous visualization of multiple electrodes, unlike

the original CARTO system that only allowed for

single-catheter tip visualization (Fig. 3). These features

also allow for fast anatomical mapping which utilizes

small fluctuations in catheter measurement of impedance.

This makes it possible to generate an electroanatomical

map and simultaneously to add electroanatomic informa-

tion without the need for point-by-point selection and

recording of electrograms. Although the system is rela-

tively new, two studies comparing various electroanatomic

mapping systems suggest the new features of the CARTO

3 results in significantly lower procedure and fluoroscopy

times than traditional fluoroscopy or older electroanatomic

mapping systems [4, 5].

3 Three-dimensional mapping systems and AF ablation

Although the original three-dimensional mapping systems

were developed prior to the era of atrial fibrillation (AF)

ablation, their widespread clinical use only occurred after it

was shown that the best outcomes of AF ablation could be

achieved with the use of three-dimensional mapping

systems to guide wide area circumferential pulmonary vein

isolation. Initial attempts at catheter ablation for AF relied

on the identification and ablation of focal triggers [6 – 8], but

it was quickly appreciated that this approach had many

limitations. These included the fact that most patients have

no active triggers during their ablation procedure and those

that did frequently had multiple foci arising from multiple

PVs. Furthermore, the approach to AF ablation directed at

arrhythmogenic foci resulted in radiofrequency (RF) delivery

within PVs which was subsequently shown to result in PV

stenosis or occlusion [9, 10].

Because of these limitations, anatomically based strate-

gies for catheter ablation of AF emerged. One of these

approaches employs a circumferential mapping catheter

which is deployed sequentially in each of the four PVs.

Although this approach was championed by several centers

throughout the world, it was ultimately discovered that the

best results of AF ablation are accomplished with an

alternate strategy, wide area circumferential ablation [11].

This strategy involves the delivery of RF energy to the

entire circumference of all PVs by the creation of circular

lesions just outside each PV ostium or the creation of two

larger circumferential lesions around the two right and the

two left PV ostia. The endpoint of this approach is complete

electrical isolation of all PVs. As these new anatomically

driven ablation strategies emerged, accurate mapping of left

atrial structure (in conjunction with local electrogram data)

Fig. 2 NavX map of the left

atrium, showing an AP view.

The left atrial appendage (dark

purple), left superior and

inferior pulmonary veins (light

purple and brown, respectively),

and right superior and inferior

pulmonary veins (tan and

yellow, respectively) are identi-

fied, and an intracardiac catheter ( green) is seen at the posterior

aspect of the left atrium

J Interv Card Electrophysiol (2011) 32:195 – 203 197



becam e paramou nt. The three-dim ensiona l map ping

systems discussed above provided (and continue to

provide) that mapping abil ity, allo wing for the safe

delineation of vital structures including the atrial walls, left

atrial appendage, pulmonary veins, and mitral annulus.

4 Image integration — from novel tool to standard

practice

4.1 Initial proof-of-concept studies

Image integration, the technique whereby three-dimensional

CT or MRI images are registered with the heart during the

mapping and ablation procedure, was first reported in 2003 in

an animal model [12, 13]. In these initial studies, we

demonstrated that a previously acquired MRI image could

be successfully registered with the animal’s heart and used to

both navigate and also deliver RF energy applications. The

following year, we reported the first human use of image

acquisition [14]. Prior to obtaining the MRI, nine standard

surface skin markers were placed on the chest and included

in the MRI image. These areas were then marked so that they

could be reapplied the following day when the procedure

was performed. Image registration, the process that super-

imposes the catheter mapping space with the MRI, was

performed by placing the ablation catheter at each skin

marker and correlating it with the corresponding imaged

marker. Registration required between 10 and 12 min. At

that point, the ablation catheter was successfully navigated

throughout the right atrium, superior vena cava, and right

ventricle. In this initial system, the catheter tip was

simultaneously displayed in coronal, sagittal, and axial

views. The accuracy of this external registration had a

precision and accuracy of 1.2 ± 0.4 and 9.5 ±4.2 mm,

respectively. Although we demonstrated the feasibility of

this approach, further optimization of position error was

required before this could be used as a standard clinical tool.

4.2 Commercial system development

The next major step in the clinical development of image

integration was the development of the CartoMerge system

by Biosense Webster and the NavX Fusion by St. Jude

Medical. We performed the initial study using CartoMerge

in a canine model to test the true accuracy of image

integration techniques for each cardiac chamber and to

evaluate its feasibility to facilitate clinical ablation proce-

dures [15]. This initial trial was performed in eight mongrel

dogs. Targeted ablations were performed at previously

placed fiducial markers guided only by reconstructed 3-D

images. At autopsy, the position error was 1.9±0.9 for the

right atrium, 2.7±1.2 for the right ventricle, 1.8±1.0 for the

left atrium, and 2.3±1.1 mm for the left ventricle. Ablations

Fig. 3 Carto3 map of the left

atrium (with CT merging; PA

projection), showing multiple

catheters projected onto the

mapping surface. A lasso map is

in the right inferior pulmonary

vein, while the ablation catheter

is below the ostium of the left

inferior pulmonary vein. The CS

catheter is also shown (belowthe LA body)




were also performed of the cavotricuspid isthmus, fossa

ovalis, and pulmonary veins. The associated position error

was 1.8±1.5, 2.2±1.3, and 2.1±1.2 mm, respectively. We

concluded from this initial evaluation of the system that

image integration with high-resolution 3-D CT allows

accurate placement of anatomically guided ablation lesions

and can facilitate complex ablation strategies.

The next step was to use this system to guide a clinical AF ablation. This was accomplished later that

year [16]. The system was successfully used to guide a

circumferential PV ablation in a 60-year-old man. And

the following year, we reported using this system to guide

AF ablation in 16 patients [17]. A preprocedure MRI was

obtained in eight patients, and a preprocedure CT scan

was obtained in eight patients. Using the CartoMerge

software package, the left atrium and PVs were segment-

ed. The segmented 3-D image was accurately registered

to the mapping space with a combination of landmark

and surface registration techniques. The registered 3-D

images were then successfully used to guide circumfer-ential PV isolation. The distance between the surface of

the registered 3-D image and the multiple electroana-

tomic p oints was 3 .0 5 ± 0 . 41 mm. T he re were n o

complications.

In a subsequent study, we evaluated with impact of heart

rhythm status on registration accuracy in a series of ten

patients [18]. Extensive mapping was performed with each

patient in both sinus rhythm and atrial fibrillation. The

results of this study revealed that registration error did not

differ between LA registrations conducted during the same

versus different rhythm as was present during CT imaging.

These findings were reassuring and suggested that, if a

patient ’s rhythm changes during an ablation procedure, the

image does not have to be reregistered.

Since publication of this small series of patients in 2006,

we have relied on image registration of previously acquired

MR or CT images to guide all of our AF ablation

procedures at Johns Hopkins (Fig. 4(a)). We also rely on

it to guide ablation of idiopathic ventricular tachycardia

(VT), ischemic VT, atypical atrial flutter ablation, and focal

premature ventricular contraction ablation, as CartoMerge

allows for image integration of all chambers and major

vascular structures that might include ablation target sites

(Fig. 4(b)).

4.3 Ultrasound imaging

Another advancement in image integration has been the

development of the CartoSound system (Biosense Webster)

that allows for image integration of electroanatomic

mapping with 3-D intracardiac echocardiogram (ICE)

through the combination of a catheter tip that has both a

navigation sensor and ultrasound phased array probe

(Fig. 5). Although ICE has been around for many years,

Khaykin et al. performed the first feasibility study

integrating it with electroanatomic mapping with the use

of Carto Sound in 2008 [19]. Traditional CT and MRI

image integration involves pre-procedure acquisition,

which is subject to distortion because of differences in

cardiac cycle [20], differences in respiratory phase [21],

atrial deformation from intraprocedure catheter manipula-

tion, or from anatomical/physiologic changes that occur

between the time of image acquisition and intraprocedure

registration [22]. Although we have previously demonstrated

prototype models for MRI use during ablation procedures

[23, 24], one of the potential advantages of ICE is that it is

the only widely available system compatible with current

electroanatomic systems that provides real-time anatomical

information. In addition, ICE acquired images merged with

electroanatomic mapping can then be merged with preproce-

dural CT or MRI. In an industry-sponsored study, Okumura

et al. found, in both a feasibility animal study and subsequent

study of ablation in 15 patients with atrial fibrillation, that

Fig. 4 (a) CartoMerge map of the left atrium, shown in PA projection.

CT imaging of the left atrium and pulmonary veins was performed

prior to electrophysiology study and ablation. Circumferential ablation

lesions (brown dots) around the PV ostia are shown. ( b) CartoMerge

image of all four cardiac chambers and associated vasculature, shown

in AP projection. RA, blue; RV, green; PA, yellow; LA, purple; LV,

aqua; aorta and coronary arteries, red




ICE constructed imaging may allow for more accurate

registration than with CT image integration alone [25].

4.4 Efficacy studies

Several studies performed to define the clinical benefit

of image integration as compared with ablation guided

only with a standard electroanatomic mapping system

have generated mixed results. Martinek et al. compared

outcomes in 53 patients who underwent ablation with a

standard mapping system versus 47 patients who

underwent ablation guided by an electroanatomic map-

ping system with image integration (CartoMerge; [26]).

The long-term success rate of catheter ablation with image

integration was 85%, compared with 68% in patients with

electroanatomic mapping alone. No PV stenosis was seen

in the patients who were ablated with image integration,

while three instances of PV stenosis were seen in the

patients whose ablation was only guided by standard

mapping. A potential flaw in the design of the study was

that the procedures were not randomized but were

performed in a sequential series fashion. This flaw was

subsequently addressed in a study by Della Bella et al.

[27]. In this report, 290 consecutive patients were

prospectively randomized to undergo ablation with stan-

dard electroanatomic mapping or with image integration

mapping. At more than a year of follow-up, AF recurrence

was less common among patients who underwent ablation

using an image integration system (19% recurrence versus

48%). They concluded that image integration results in

superior long-term outcomes. A similar improvement in

the efficacy of AF ablation guided by image integration

has also been reported by Bertaglia et al. [28] and by

Hunter et al. [29].

Other studies of image integration have yielded negative

results. In a prospective study, Kistler et al. randomized 80 patients with AF to undergo first-time ablation using

standard mapping alone or with CT image integration

(CartoMerge) [30]. They found no significant difference in

single procedure success at 6 months between the electro-

anatomic mapping (56%) and image integration (50%)

groups ( P =0.9). The complication rate was similar, and

there was one case of PV stenosis seen in the standard

mapping group compared with no cases in the image

integration group. Similarly, studies by Tang et al. and

Caponi et al. also found no difference in clinical outcomes

at 12 months with the use of CT and MRI image integration

system, respectively, and both showed similar complicationrates [31, 32]. However, although there was no difference in

clinical outcome of the arrhythmia, both of these studies did

find significantly reduced fluoroscopy time in the image

integration groups.

5 Image fusion of scar maps to guide ablation of VT

and atrial fibrillation

The next step in the development and utilization of image

integration software to guide ablation has been the

incorporation of scar maps from previously acquired

positron emission tomography (PET) or MRI images.

Dickfeld et al. were the first to report this in 2008 [33]. In

this initial series, 14 patients underwent PET/CT multi-

modality imaging before VT ablation. The PET/CT-derived

scar maps were used to characterize myocardial scar using a

17-segment analysis and surface reconstruction. In ten

patients, reconstructed 3-D metabolic scar maps were

integrated into a clinical mapping system and compared

with high-resolution voltage maps. A good correlation was

found between the PET/CT-derived scar maps and the

voltage maps. They also demonstrated that 3-D metabolic

scar maps accurately displayed endocardial and epicardial

surfaces and could be successfully integrated with a

registration error of 3.7±0.7 mm. These authors found that

a combination of visual alignment and surface registration

was most accurate for myocardial scar accounting for <15%

of the LV surface. Voltage map findings correlated closely

with scar size, location, and borderzone. Integrated scar

maps revealed metabolically active channels within the scar

not detected by voltage mapping and correctly predicted

non-transmural scar despite normal endocardial voltage

Fig. 5 CartoSound image of the left atrium and pulmonary veins,

shown in right superior PA view. Circumferential ablation around the

PV ostia and across the LA roof is shown ( brown dots) [25]




recordings. These authors concluded that PET/CT fusion

imaging is able to accurately assess left ventricular scar

and its borderzone. They also showed that the integra-

tion of a 3-D scar map into a clinical mapping system

is feasible and may allow supplementary scar character-

ization that is not available from voltage maps alone.

They further predicted that this system could facilitate

substrate-based VT ablation. In a subsequent study, Tianet al. published a case report describing a 57-year-old

man with a prior myocardial infarction who was

scheduled for VT ablation [34]. Prior to the procedure,

a PET/CT was obtained. The 3-D PET/CT LV and scar

data sets, as well as the delayed-enhancement MRI (DE-

MRI) 3-D reconstruction were co-registered. The 3-D CT

images allowed identification of the LV wall thickness and

epicardial and endocardial surfaces. Wall thinning was

observed only in areas with decreased endocardial voltage

or <1.5 mV, suggestive of scar or borderzone. The 3-D

PET images showed metabolic scar and borderzone at the

apex and the inferior wall that matched the voltage-derived areas of scar and borderzone. The DE-MRI scar

locations were consistent with the voltage-derived scar;

however, the MRI scar was 20% to 30% larger. No VT

could be induced, so a substrate-guided ablation procedure

was performed. Mapping was guided by the registered 3-D

scar. This study was important as it described, for the first

time, the use and value of integrating scar images from a

prior MRI or PET scan, co-registering them with a CT

image and using these data to help guide VT ablation.

More recently, Tian et al. used a contrast-enhanced CT

scan to identify scar. In a series of 11 patients, they

demonstrated that they could characterize LV anatomy and

3-D scar/borderzone substrate [35]. Integration of these

3-D data sets into a clinical mapping system provided

supplementary information as compared with voltage

mapping alone.

In addition to these investigators, our group at Johns

Hopkins has also been pursuing scar imaging and registra-

tion of these images to guide VT ablation. However, instead

of using contrast CT scans to characterize scars, we have

been using delayed-enhancement MRI imaging. We have

previously shown in an animal model that MRI images

accurately correlate with scar and can also correlate well

with inducible VT circuits [36]. We have also characterized

scar patterns in patients with cardiomyopathy (Fig. 6). We

are now embarking on a prospective randomized clinical

trial to determine if importing scar into an electroanatomic

mapping system improves the outcomes of VT ablation. In

our opinion, this is very likely to become a clinically

valuable tool.

The next step will be to use the same approach for

AF ablation procedures. A challenge that must be

faced, however, is the greater difficulty in visualizing

scar in the thin-walled atrium as compared with the

ventricle. However, recent advancements in cardiac

MRI have allowed for better visualization of the atrium

following ablation procedures [37]. McGann et al.

looked at 46 patients undergoing pulmonary vein isola-

tion for AF and took DE-MRI images before and 3 monthsafter ablation. They found that recurrence of AF at

3 months correlated with the degree of wall enhancement

with >13% injury in the LA predicting freedom from AF

[38]. A subsequent study by Badger et al. confirmed these

findings that higher total LA scar correlated well with

reduced AF recurrence. In addition, they demonstrated

that DE-MRI integration could be used to identify the

location of gaps or recovery in previous ablation scar that

could be potentially used as targets in repeat ablation

procedures [39]. Further studies will need to be done to

investigate the clinical application of DE-MRI in guiding

AF ablation procedures and how this will impact clinical

outcomes.

6 Conclusion

Fusion of imaging technologies or image integration has

been shown to be a highly valuable tool in performing

circumferential AF ablation. Although there have been

mixed results, several studies have reported improved

long-term outcomes, and this approach is now relied on

around the world at many centers to guide AF ablation.

The next step forward is to employ a technique that

allows the myocardial scar to be co-registered with a

surface shell to facilitate the ablation of ventricular

tachycardia and also atrial fibrillation. Several centers,

including ours, now routinely register scar images to

guide VT ablation and we anticipate that this approach

will rapidly spread to other centers, and the final step

will be to use this approach to guide AF ablation,

especially in patients who are undergoing repeat AF

ablation procedures.

Fig. 6 MRI of the left atrium and ventricle. Mid-myocardial scar in

the ventricular septum is shown (white defect ) [36]




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Govil, Calkins, Spragg - 2011 - Fusion of Imaging Technologies How, When, And for Whom-Annotated

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