pplication of nuclear medicine techniques to conduction anomalies has been studied through the use ofgated blood-pool studies (1—12).Functional imaging,in particular, is a unique approach used in nuclearcardiology, where specific parameters are extracted anddisplayed as maps. Phase analysis, one ofthe functionalimaging techniques, provides a parameter that corresponds to the sequence of contraction. Although phaseimaging does not directly assess electrical excitation,generally good agreement between excitation and mechanical contraction has been described (3—11).Sinceconventional phase image in planar gated blood-poolstudies is based on the time-activity curve that is basedon the movement ofthe blood pool, three-dimensionaloverlap of radioactivity cannot be avoided, and therefore there is a limitation to tracing the exact contractionsequence.

Tomography seems to be a more reasonable technique for the three-dimensional evaluation of contraction patterns (12). We have developed a length-basedFourier analysis (LFA) for the analysis of contractionand excitation using tomographic gated blood-pool

Received May 10, 1985: revision accepted Feb. 26, 1986.For reprints contact: Kenichi Nakajima, MD, Department of

Nuclear Medicine, School ofMedicine, Kanazawa University, 13-I Takara-machi, Kanazawa, 920, Japan

studies (13). The purpose of this study is to evaluatethe utility of the LFA for the detection of the accessoryconduction pathway (ACP) in the pre-excitationsyndrome (Wolff-Parkinson-White (WPW) syndrome).

METHODS

Study GroupThe study group consisted of 22 patients with pre

excitation syndrome who were considered for the surgical division of the ACP because of frequent episodesof tachycardia, a history of heart failure, and/or loss ofconsciousness. As preoperative studies, all patientsunderwent routine 12-lead ECGs, electrophysiologicstudies using i.v. catheters, radionuclide studies, andepicardial mapping. The final diagnosis for the locationof the ACP was confirmed by the epicardial mappingand the result of surgery. The patients were classifiedinto four groups according to the location of ACP,including five right cardiac types, three right septaltypes, ten left cardiac types, and four with multipleACPs. Of the four with multiple ACPs, three had anACP on each side, one had two ACPs on the right side.In a patient with two ACPs, ECO showed right cardiactype in the first study, and left type in the second studysoon after a pacing study. A control group consisted of

1131Volume27 •Number7 •July1986

Length-Based Fourier Analysisin the Pre—ExcitationSyndromeKenichi Nakajima, Hisashi Bunko, Norihisa Tonami, Junichi Taki, Ichiro Nanbu,Yasushi Shiire, Kinichi Hisada, Takuro Misaki, and Takashi Iwa

Department ofNudear Medicine and First Department ofSurgery, School of Medicine,Kanazawa University, Kanazawa, Japan

Length-based Fourier analysis (LFA) was applied to tomographic gated blood-pool study, andphase and percent-shortening diagrams were generated. In 22 patients with pre-excitationsyndromeandten controlsubjects,the mostbasalshort-axissectionwas usedfortomographic analysis. When the initial abnormal phase was considered as the location ofaccessoryconductionpathway(ACP),correctdiagnosisfor the localizationo?ACPwas givenin 19 of 22 patients. In ten control subjects, no specific segments of initial phase were noted,although six patients had initial phase in the septal or paraseptal segments. The tomographicLFA was more effective for pinpointing the segment of the earliest phase than tomographiccount-basedphaseanalysis.TheLFAprovidedobjectivethree-dimensionalinformationforcontraction sequence. Because movements of ventricular edges are essential in tomography,the LFAwasconsideredto be a reasonableapproachfor the analysisof tomographicgatedblood-pool study.

J NuciMed 27:1131—1137,1986

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ten patients who had neither conduction anomalies norventricular contraction abnormalities. Associated cardiac diseases were: Ebstein's anomaly (n = 1), coronaryartery disease with 75% narrowing of the left anteriordescending artery (n = 1), and corrected transpositionofthe great arteries (n = 1). The remaining patients hadno other cardiac complications. In this study, the differentiation of pre-excitation and normal conductionwas based on the ECG and electrophysiologic data. Nonuclear medicine criteria was used to separate thegroups.

Gated Blood-Pool Studies and Gated EmissionComputed Tomography

Routine gated blood-pool studies (0BPS) and gatedemission computed tomography (GECT) were performed using technetium-99m (99mTc)red blood cellsby an in vivo labeling method. Fiftee@ minutes afterinjection of stannous pyrophosphate solution, 25 mCiof [99mTc]pertechfletate were injected intravenously.ECO-gated blood-pool data were acquired in 64 x 64matrices with 24 frames/cardiac cycle in modified (10°caudal tilt) left anterior oblique (LAO) 35°,right anterior oblique (RAO) 35°,and left lateral views. The dataacquisition time was 10 mm for LAO view and 5 mmfor the latter two views. The GECT system consisted ofdual-headed scintillation cameras' equipped with highresolution collimators interfaced to a minicomputer@.Thirty-six projection data with 12 frames/cardiac cycle

were stored on magnetic disk. Each projection datumwas collected for 1 mm. Since dual cameras were employed, actual acquisition time was 18 mm. Serial shortaxis images perpendicular to the long axis of the heartwere reconstructed using a filtered backprojection algorithm supplied by the manufacturer. Full width athalf maximum of the system was 15 mm at the centerof rotation when the rotation radius was 23 cm.Attenuation correction was not performed.

Tomographic Count-Based Phase AnalysisThe same algorithm of phase analysis that has been

applied to the conventional planar 0BPS was utilizedfor tomographic images (1,12). Phase and amplitude ofthe fundamental frequency calculated from the timeactivity curve in each pixel were mapped as functionalimages. When we consider the nature of tomographicimages, the phase data interior to the end-systolic perimeters are meaningless. Therefore, we only evaluatedthe periphery of the phase images, that was outside ofthe end-systolic boundaries. We assumed that pre-excitation was associated with the earliest inward movement of the edges. The segment of the earliest phaseidentified on the serial short-axis phase images werejudged as the site of ACP.

Length-Based Fourier AnalysisThe algorithm of the length-based Fourier analysis

was (LFA) described (13). This algorithm was made upof five parts as follows.

%LS

FIGURE 1Length-based Fourier analysis (LFA) in normal subject. LFA was performed in most basal sliceventricles.Eachconcentriccircledenotes90°in phaseand 25% in %LS. In this diagram,minimalright anterior septal region (arrow). Left septal segments are excluded because %LSs are <5%

ED ESED ES

on both sides ofphaseisfoundin

1132 Nakajima,Bunko,Tonamietal TheJournalof NuclearMedicine

PHASE PHASE %LS

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DetectionNo.of patients

Siteof ACP (No.of ACP)byLFAt

(No.ofACP)Right

55Rightseptal33Left108Multiple

1 (2, rightandleft)1(2)1(2,rightandleft)1(1)1(2, rightandleft)1(1)1(2, rightandleft)0(0).

ACP = Accessory conductionpathway.t

LFA = Length-based Fourier analysis.

I . Isolation of chambers. In order to exclude surrounding structures, a region of interest (ROl) was setusing a track-ball. With the use of this ROI as a mask,the background outside the ROI was set to 0.

2. Determination of the center. A center of gravitywas determined by weighting the amount of activity ineach pixel inside of a certain threshold count (usually60% of the maximum count). This fixed point in thefirst frame was defined as a center throughout a wholecardiac cycle. If this center was out of end-systolicperimeter, it was set inside manually.

3. Calculation of time-length curve (TLC). Thelengths from a center to ventricular edges were measured and TLCs were generated in 60 radial directions.

4. Calculation of length-based phase. Phase and amplitude of the discrete Fourier transform based on thefirst harmonic. Percent length-shortening (%LS) wasdefined as:

%LS = 2 x amplitude x lOO/(DC + amplitude),

where DC is a direct current component ofthe Fouriertransform. This analysis was performed in 60 segments(6°step).

5. Display ofthe result. Length-based phase and %LS

in 60 radial directions were displayed using polar coordinates as shown in Fig. 1. Segment zero is definedas the right horizontal direction (3 o'clock) from thecenter and the segment numbers increasecounterclockwise.

Only the basal, short-axis slices were analyzed by theLFA. Although eight short-axis slices may have beenselected, only the most basal section was used. Theearliest length-based phase was considered to be thelocation of ACP in the WPW syndrome. The segmentsthat showed %LS < 5% were excluded, because thereliability of phase was low in the segments of reducedcontractility.

The range of length-based phase, defined as the difference of maximum and minimum phase in a basalslice, was calculated in each patient. In this analysis,right septal types were included in the right cardiactypes. In the left cardiac types, a patient with transposition of the great arteries was excluded, because theshape of right and left ventricles were reversed in thisanomaly. The ranges of length-based phase in the control patients were also calculated in both sides of theventricles.

Epicardial Mapping and SurgeryThe location of ACP was investigated by epicardial

mapping during surgery (14). Using electrode catheterwith six pairs of bipolar electrodes, activation on acardiac surface was analysed by computerized recorder.The earliest epicardial activation on the cardiac surfacewas determined. The retrograde atrial activation wasanalyzed during reciprocating tachycardia or ventricular pacing. In this way, the localizations of the ACPs

TABLE 1Detectability of Site of ACP by LFA

were determined. After the site of ACP was surgicallytransected, the ECG changed to the normal conductionpattern in all patients. Ifthe distance between a segmentof the earliest phase and the actual site of the ACP waswithin one eighth of an atrioventricular ring, it wasjudged as a correct diagnosis.

Statistical AnalysisThe results of the range of length-based phase were

described as mean ±s.d. The significance of the difference among the mean values was assessed with ananalysis of variance and Student's t-test.

RESULTS

Detectability of the site of ACP was summarized inTable 1. Five of five patients with right cardiac typeand three of three with septal ACPs were correctlydiagnosed. In ten ACPs with left cardiac type, eightwere correctly identified on the LFA. An ACP thatfailed to be detected was located on the left posterolateral segment; however, the earliest length-based phasewas in segment 16 (anterior wall). The other undetectedACP was located on the left posterior segment, whereasthe earliest phase was in segment 1 (lateral). Fourpatients with multiple ACPs were included in our studygroup. In a patient with an ACP on each side, ECOshowed right cardiac type in the first study, and theLFA demonstrated the earliest phase in segment 43(right posterior). After an intracavitary pacing study inthis patient, ECG showed left type, then radionuclidestudy with GECT was repeated. At this time, the earliestphase was identified at segment 54 (left posterolateral)in the left heart. These locations were in agreementwith the ACP sites surgically confirmed. One of twoACPs was detected in two patients, and none ofthe twowere identified in a patient. Overall diagnostic sensitivity for detecting the sites of ACPs was 19 of 22 patients(86%). Regarding the ACP sites, 77% (20 of 26 ACPs)were detected.

Tomographic count-based phase analysis had the

1133Volume27 •Number7 •July1986

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IIR L

PA

St PH @LS1 002 00

3 180 5

4 160 75 145 76 128 77 114 88 111 129 114 18

10 116 2511 11? 3012 117 3313 116 3314 115 3115 113 2816 113 261? 115 2418 118 2219 124 2020 133 1921 141 1922 148 2123 152 2324 155 2325 159 2226 163 2127 166 2128 166 2229 166 2430 165 24

@:PH @.LS31 164 2232 158 2033 147 2034 136 2135 131 2436 130 2437 133 2238 138 1939 143 1740 146 1541 144 1342 140 1343 137 1244 138 1345 144 1446 153 1647 160 1848 165 1849 165 1650 156 1251 126 952 94 1153.-84 1554 86 1655 95 1556 108 1457 123 1158 136 959 150 660 0 0

%LS

ED ES

B _

FIGURE 2A: Planarand tomographiccount-basedphaseimages.B: LFA in patientwith right posteriorparaseptalACP.Phaseimages are displayed in isocount display with gray scales, and earliest phase corresponds to white region. Earliestphasewas noticed in midportionof right ventriclein LAO view and in posterolateralregion in RAO view (above).Tomographic short-axis phase image apparently showed earliest contraction in right posterior paraseptal segment(arrow). In LFA, earliest segment was No. 53, that was in agreement with surgically confirmed location of ACP

L.LATRAOLAO

Tomographic Short Axis

PHASE

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@- —- —.-@

wPw righttypeRV869.833.9lefttypeLV946.821.7ControlRV1O

LV1O58.2 33.614.3lO.2@.vs.tp<0.05.

A B C D

FIGURE 3Resultsof length-basedphasein patientswith posteriorand anteriorseptalACPs(A and B) and left posteriorandlateral ACPs (C and D). Arrows in polar coordinate displays indicate segments of earliest phase and those in lowershort-axis blood-pool images correspond to location of earliest segments. Stars are sites of surgically confirmed ACPs.Note close correlations between length-based phase and site of ACP

same detectability for localizing the ACPs. However, intomographic phase images, the earliest region was extended to several segments, sometimes more than onefourth of an atrioventricular ring. The point of initialactivation demonstrated by the LFA was in good agreement with one or several earliest segments shown in thecount-based phase image. However, we think tomographic length-based presentations would makelocalizations simpler than with the count-basedmethod.

In ten control subjects, no specific segments of theearliest contraction were found. The earliest segmentswere: two in the right free wall, four in the right septalor paraseptal, two in left free wall, and two in the leftseptal or paraseptal regions. Six of ten patients hadinitial phase in the septal or paraseptal segments. Anexample of LFA in a normal subject is shown in Fig. 1.

Table 2 shows the range of phase in each group. Theranges of phase (deg) in the WPW syndrome and control subjects were 69.8 ±33.9 and 58.2 ±14.3 in the

TABLE2Rangeof Length-BasedPhasein BasalSlice

Group No. mean(°) s.d.(°)

right ventricular basal slice, and 46.8 ±2 1.7 and 33.6±10.2 in the left ventricular slice. The ranges of phasewere larger in the WPW syndrome than in controlsubjects; however, the differences were not statisticallysignificant. The range of phase distribution of the rightventricle showed significantly larger values than that ofleft ventricle in control patients (p < 0.05).

A patient with right posterior paraseptal ACP wasshown in Fig. 2. Some examples of the LFA and thelocations of ACPs confirmed by epicardial mappingand surgery were indicated in Fig. 3.

DISCUSSION

Gated blood-pool study and phase images have beenapplied to conduction anomalies and pacing studies toanalyze the relations of electrical excitation and mechanical movement (2—11).Although the propagationpattern of the phase is not the conduction pathwayitself, it has been applied to conduction disorders because sequence of motion is generally parallel with thatof conduction. In the WPW syndrome, we have attempted to detect the location of accessory conductionpathway with the use ofphase image analysis. However,the planar phase analysis was considered to be unsatisfactory for localizing the precise sites of ACPs even bymultiple projections (8,12). Tomographic gated bloodpool study with count-based phase analysis improvedthe diagnostic accuracy for localization of ACP (12).But tomographic count-based phase analysis (TCP) hadsome methodological problems as described later.

1135Volume27 •Number7 •July1986

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Therefore, we developed the algorithm, length-basedFourier analysis (13).

TomographicCount-Based Phase AnalysisOne of the advantages of the TCP is that the same

program that has been utilized for phase analysis isavailable in many nuclear medicine computer systems.In a previous study, we divided the most basal sectioninto eight segments on each side and the identificationof initial phase in the segment in which the ACP waslocated, or adjacent to it, was judged as the correctdiagnosis (12). With these lax diagnostic criteria, thedetectability of ACP was 12 of 14 (86%) patients.However, it was difficult to indicate an earliest segment,or to pinpoint the location. Another methodologicalproblem is in the use of count-based phase analysis forthe tomographic images. Considering the characteristicof tomography, the theoretical time-activity curves inside of the end-systolic boundary must be flat. Actuallythey are not flat because of the effect of spatial filteringand reconstruction process. When we observe only theperiphery ofcardiac chambers, however, the TCP couldbe an effective method because of the movements ofthe edges reflected on the phase value in the border ofthe cardiac chambers.

Length-Based Fourier AnalysisAnalyses of time-length curves from a center to yen

tricular edges are considered to be appropriate, becausethe information of edges is essential in tomographicimages. Pinpointing of the earliest segment was easilyperformed by the LFA automatically. Generally, thedifference between the surgically confirmed site of ACPand the earliest segment of length-based phase was atmost one-eighth of an atrioventricular ring. In TCP,the septal or paraseptal segment is usually inside of thephase image, and we must be careful in the interpretation of these regions. On the other hand, in the LFA,the movement of septal border was easily recognized.However, ifthe percent shortening in the septal segmentis small (we defined < 5% as akinetic), they are notinterpreted. As shown in this study, the LFA can be areliable diagnostic method for the localization of ACPs.Initial site of contraction and its sequence were objectively assessed. Moreover, this approach can be appliedto the other cardiac contraction abnormalities as wellas conduction disorders, because three-dimensionalinformation is available without overlap ofblood pools.

LFA in Normal SubjectsThere were no specific segments of initial phase in

normal subjects when the basal sections were analyzed.However, six of 10 patients had initial contraction inseptal or paraseptal regions. This finding was consistentwith the planar phase analysis (6,9). Therefore, in orderto differentiate the conductions with normals and bypass tracts, the difference of phase between right and

left ventricles is important. This differentiation can beachieved even by the planar gated blood-pool study inthe LAO view. Additionally, the ECG patterns duringradionuclide study were useful to confirm the presenceofdelta waves, short PR intervals, and wide QRS cornplexes. If the ECG did not show the pre-excitationpattern, the earliest segment of the phase in a chamberdid not indicate the location of ACP.

Range of Phase in WPW Syndrome and NormalsThe range of the length-based phase in the pre

excitation showed larger values than that of normalatrioventricular conduction, although they were notsignificant. This finding can be explained by the fusionof excitation through an ACP and normal conductionpathway. However, the separation of the WPW syndromes from normal patients were not good. This isdue in part to the fact that the LFA was performed onlyin the basal slice, whereas actual contraction spreadsover the whole myocardium. Therefore, the LFA shouldbe carried out over the whole cardiac surface on bothsides of heart. To overcome this limitation, a newprogram for making phase maps over the whole cardiacsurface will be required. However, in definite WPWsyndrome with characteristic ECO patterns and significant phase difference ofboth ventricles in planar phaseimage, the LFA can provide reliable information on theACP sites.

The phase distribution of right ventricular basal slicewas significantly larger than that of left ventricle. Asshown in Figs. 1, 2, and 3, the phase diagrams in theleft ventricle was more circular than in the right ventricle. The shape of the right ventricular basal slice had asemilunar shape and right ventricular outflow tract wassometimes included. A larger distribution of phase inthe right ventricle may be explained by the complexityof right ventricular shape and motion.

Factors Affecting LFAThree major factors can influence the result of the

LFA. First, the LFA reflects the motion abnormality.Myocardial ischemia or fibrosis, for example, may affectthe wall motion, that causes an abnormal length-basedphase. A patient with low ejection fraction or lowpercent-shortening must be carefully interpreted. Secondly, certain conduction anomalies other than preexcitation, such as bundle branch block, may affect thephase pattern. Even in the WPW syndrome, the degreeof pre-excitation is different in each patient. The contraction sequence of the WPW syndrome is the fusionof multiple conduction pathways. If the patients areconcealed types with only retrograde conduction orintermittent types without delta waves, they will shownormal contraction patterns. The third factor is intechnical problems. Although the spatial resolution inour system was 15 mm in full width at half maximumand temporal resolution for acquisition was 12 frames

1136 Nakajima,Bunko,Tonamietal The Journal of Nuclear Medicine

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invasive identification of initial site of abnormalventricular activation by least square phase analysis ofradionuclide cineangiogram. Circulation 65:1511—1518,1982

5. Botvinick EH, Frais MA, Shosa DW, et al: Accuratemeans of detecting and characterizing abnormal patterns ofventricular activation by phase image analysis.Am J Cardiol 50:289—298,1982

6. Chan WWC, Ka1ffV, Dick M II, et al: Topography ofpreemptying ventricular segments in patients withWolff-Parkinson-White syndrome using scintigraphicphase mapping and esophageal pacing. Circulation67:1139—1145,1983

7. Swiryn 5: Nuclear electrophysiology. PACE 6:1171—1180,1983

8. Nakajima K, Bunko H, Tada A, et al: Phase analysisin the Wolff-Parkinson-White syndrome with surgically proven accessory conduction pathways. J Nuc/Med25:7—l3,1984

9. Botvinick E, Frais M, O'Connell W, et al: Phase imageevaluation of patients with ventricular pre-excitationsyndromes. J Am Coil Cardio/ 3:799—814, 1984

10. Bashore TM, Stine RA, Shaffer PB, et al: The noninvasive localization of ventricular pacing sites byradionuclide phase imaging. Circulation 70:681—694,1984

11. Links JM, Raichlen JS, Wagner HN Jr. et al: Assessment of the site of ventricular activation by Fourieranalysis of gated blood-pool studies. J Nuci Med26:27—32,1985

12. Nakajima K, Bunko H, Tada A, et al: Nuclear tomographic phase analysis: localization of accessory conduction pathway in patients with Wolff-ParkinsonWhite syndrome. Am Heart J 109:809—815, 1985

13. Nakajima K, Bunko H, Tonami N, et al: Quantification ofsegmental wall motion by length-based Fourieranalysis.J Nuc/Med 25:917—921,1984

14. Iwa T, Kawasuji M, Misaki T, et al: Localization andinterruption of accessory conduction pathway in theWolff-Parkinson-White syndrome. J Thorac Surg80:271—279,1980

in a cardiac cycle, they were practically effective asshown in this study. As is seen in planar gated bloodpool study, arrhythmia during data acquisition, theshape of the time-length curve; and order of harmonicsall affect the result of phase analysis. The overlap ofblood pool, however, which is one of the major causesof inaccuracy, was avoided in tomography.

CONCLUSION

The LFA in gated blood-pool tomography detectedthe site of ACP in 86% (19/22) of patients with WPWsyndrome, and was effective for pinpointing the earliestsegment. It will also be helpful for analyzing threedimensional pattern of contraction sequence withvarious cardiac diseases.

FOOTNOTES

a Shimadzu Corporation (ZLC 75), Tokyo, Japan.

t Shimadzu Corporation (Scintipac 2400), Tokyo, Japan.

REFERENCES

1. Adam WE, Tarcowska A, Bitter F, et al: Equilibrium(gated) radionuclide ventriculography. Cardiovasc Radio/2:l61—l73,1979

2. Links JM, Douglass KH, Wagner HN, Jr Patterns ofventricular emptying by Fourier analysis of gatedbloodpoolstudies.J Nuc/Med 21:978—982,1980

3. Swiryn 5, Pavel DO, Byrom E, et al: Sequential regional phase mapping of radionuclide gated biventriculogram in patients with left bundle branch block.Am HeartJ102:1000—1010,1981

4. Turner DA, von Behren PL, Ruggie NT, et al: Non

1137Volume27 •Number7 •July1986

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1986;27:1131-1137.J Nucl Med.   Misaki and Takashi IwaKenichi Nakajima, Hisashi Bunko, Norihisa Tonami, Junichi Taki, Ichiro Nanbu, Yasushi Shiire, Kinichi Hisada, Takuro  Length-Based Fourier Analysis in the Pre-Excitation Syndrome

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