Clinical Validation of Technetium-99m MIBI-Gated Single-Photon EmissionComputed Tomography (SPECT) for Avoiding False Positive Results in Patientswith Left Bundle-Branch Block: Comparison with Stress-Rest Nongated SPECT

HAKAN DEMIR, M.D., GÜNER ERBAY, M.D., K. METIN KIR, M.D., KENAN OMURLU, M.D.,* FATMA BERK, M.D., M.SC.,† CUMALI AKTOLUN, M.D., M.SC.†

Ankara University School of Medicine, Department of Nuclear Medicine; *Ankara University School of Medicine, Department ofCardiology, Ankara; †Kocaeli University School of Medicine, Department of Nuclear Medicine, Kocaeli, Turkey

Summary

Background: Septal perfusion defects are common on my-ocardial perfusion single-photon emission computed tomog-raphy (SPECT) slices in patients with left bundle-branchblock (LBBB) in the absence of coronary artery disease.

Hypothesis: The use of gated myocardial perfusion SPECTimaging in such patients should be clinically validated. Theaims of this study were, therefore, to validate clinically the useof gated myocardial SPECT imaging to avoid false positiveseptal perfusion defects in patients with LBBB and to comparenongated and gated SPECT imaging techniques in the samepatients in the same imaging session.

Methods: We performed stress-rest myocardial perfusionSPECT and resting gated SPECT using Technetium-99mMIBI in 25 patients with LBBB and in 6 control subjects.Stress-rest SPECT images and end-diastolic and end-sys-tolic gated SPECT slices were assessed visually and quanti-tatively (septum/lateral wall count ratio). Coronary angiog-raphy was performed in 15 patients with LBBB and in all 6control subjects.

Results: Stress-rest (nongated) SPECT slices and end-dias-tolic and end-systolic gated SPECT images were normal in allcontrol subjects. Stress-rest (nongated) SPECT imaging re-vealed septal perfusion defect in 20 (11 reversible, 9 irre-

versible) patients with LBBB, whereas the figures were 15 and5 for end-systolic and end-diastolic gated SPECT images, re-spectively. Coronary angiography results were normal in allcontrol subjects and in 15 patients with LBBB. Quantitativeanalysis of gated SPECT images revealed no statistically sig-nificant difference between patients with LBBB and controlsubjects in end-diastolic mean septum/lateral wall count val-ues (0.86 ± 0.19 in LBBB vs. 0.98 ± 0.15 in normal subjects,p > 0.05), but the difference was statistically significant forend-systolic, stress, and rest values (p<0.001 for all).

Conclusion: Gated SPECT imaging, particularly end-dias-tolic images, revealed fewer false positive results and thus canbe used to avoid false positive septal perfusion defects com-monly seen in stress-rest (nongated) myocardial perfusionSPECT in patients with LBBB.

Key words: SPECT, myocardium, gated SPECT, Tc-99mMIBI, left bundle-branch block

Introduction

From an imaging point of view, septal perfusion defectcommonly seen in patients with left bundle-branch block(LBBB) is a common cause of false positive results of myo-cardial perfusion single-photon emission computed tomog-raphy (SPECT) in patients with LBBB. These perfusion ab-normalities may be seen even on rest SPECT images. Themechanism of perfusion abnormalities in these patients is yetto be clearly understood.1 In the absence of signs and symp-toms of ischemic heart disease, false positive perfusion de-fects in the septum in this group of patients decrease the relia-bility of myocardial perfusion studies with both thallium-201(201Tl) and technetium-99m methoxy isobutyl isonitrile(99mTc MIBI).2–13

Gated SPECT imaging allows the simultaneous examina-tion of left ventricular myocardial perfusion and wall thicken-ing.14–17 Taking the possible pathophysiologic mechanisms ofthe LBBB and the proposed mechanisms for false positiveperfusion defects into consideration, it was suggested that gat-

Clin. Cardiol. 26, 182–187 (2003)

Address for reprints:

Cumali Aktolun, M.D., M.Sc.Professor of Nuclear Medicine,Department of Nuclear MedicineKocaeli University School of MedicineDerince, Kocaeli, TR-41900 Turkey e-mail:aktolun@ttnet.net.tr

Received: September 21 2002Accepted with revision: April 22, 2002

H. Demir et al.: Tc-99 MIBI-gated SPECT in patients with LBBB 183

ed SPECT would avoid the false positive results, exploiting itsability to study simultaneously regional myocardial perfusionand wall thickening.1

The aims of this study were (1) to validate the clinical use of99mTc MIBI-gated SPECT in patients with LBBB to avoidfalse positive perfusion defects, and (2) to compare the resultsof gated SPECT with those of stress-rest nongated SPECT inthe same patients in the same imaging session.

Materials and Methods

Patient Population

In all, 25 consecutive patients (13 men, 12 women, agerange 41–71 years, mean age 60.4 ± 7.4) with LBBB and 6control subjects (1 man, 5 women; age range 43–53 years,

mean age 49.1 ± 3.8) were included in this prospective study(Table I). We excluded patients with previously diagnosedcoronary artery disease, hypertension, cardiomyopathy, valvu-lar heart disease, myocardial infarction, and any electrocardio-graphic abnormality except for LBBB. All patients had a lowlikelihood of coronary artery disease. Normal coronary angio-graphy results were obtained in control subjects prior to theirreferrals to nuclear medicine for gated SPECT imaging; the indication for performing coronary angiography (CAG) wasatypical chest pain.

Imaging Protocol

Stress-rest myocardial perfusion SPECT: Technetium-99mMIBI myocardial perfusion SPECT imaging using stress-restsame-day protocol was performed both in patients with LBBBand in control subjects.18, 19 According to the patients’ needs,

TABLE I Cumulative data of visual interpretation and quantitative analysis of nongated SPECT and gated SPECT images

End- End- Stress Rest systolic diastolic End- End-

Stress CAG perfusion perfusion perfusion perfusion Stress Rest systole diastole No. Patients Age Sex type result defect defect defect defect S/L S/L S/L S/L

1 Control 50 F E Normal (�) (�) (�) (�) 0.90 0.90 0.96 1.002 Control 53 F D Normal (�) (�) (�) (�) 0.96 0.98 0.97 0.963 Control 52 M D Normal (�) (�) (�) (�) 0.95 0.97 0.95 0.994 Control 51 M D Normal (�) (�) (�) (�) 0.97 0.98 0.98 0.995 Control 46 F E Normal (�) (�) (�) (�) 0.95 0.95 0.96 1.006 Control 43 F E Normal (�) (�) (�) (�) 0.86 0.86 0.92 0.987 LBBB 61 F E NP (�) (�) (+) (�) 0.78 0.80 0.38 0.818 LBBB 64 M E Normal (+) (+) (+) (�) 0.62 0.63 0.63 0.849 LBBB 70 M D Normal (�) (�) (+) (+) 0.91 0.92 0.56 0.61

10 LBBB 71 M E NP (+) (+) (�) (�) 0.69 0.70 0.79 1.2111 LBBB 70 F E Normal (+) (+) (�) (�) 0.77 0.79 0.93 1.2712 LBBB 54 F E NP (+) (+) (�) (�) 0.68 0.70 0.76 0.8513 LBBB 68 M E Normal (+) (�) (+) (�) 0.67 0.80 0.44 0.8014 LBBB 61 M E Normal (+) (�) (�) (�) 0.80 0.86 0.86 1.1515 LBBB 62 M D NP (+) (+) (+) (�) 0.74 0.75 0.63 0.7016 LBBB 64 F E Normal (+) (+) (+) (�) 0.70 0.71 0.55 0.9417 LBBB 58 F E NP (+) (+) (+) (�) 0.84 0.84 0.66 1.0918 LBBB 47 M E NP (�) (�) (+) (+) 0.91 0.90 0.46 0.6119 LBBB 66 M E Normal (+) (�) (+) (�) 0.72 0.81 0.62 0.7320 LBBB 55 F D Normal (+) (�) (+) (+) 0.71 0.85 0.58 0.7221 LBBB 64 F D Normal (�) (�) (�) (�) 0.78 0.78 0.76 0.9922 LBBB 56 M E Normal (+) (�) (+) (�) 0.62 0.70 0.48 0.7623 LBBB 60 M E Normal (+) (+) (+) (+) 0.44 0.62 0.40 0.6224 LBBB 50 F E NP (+) (+) (�) (�) 0.84 0.83 0.79 1.0625 LBBB 65 F E Normal (�) (�) (+) (�) 0.76 0.78 0.70 0.9226 LBBB 41 F E Normal (+) (�) (+) (�) 0.67 0.74 0.61 0.8027 LBBB 52 F E NP (+) (+) (+) (�) 0.73 0.75 0.60 0.8428 LBBB 65 M D Normal (+) (�) (�) (�) 0.89 0.93 1.03 1.0329 LBBB 65 M D Normal (+) (+) (+) (+) 0.61 0.61 0.55 0.6530 LBBB 60 F D NP (+) (�) (+) (�) 0.84 0.92 0.65 0.8531 LBBB 62 M E NP (+) (+) (+) (+) 0.56 0.59 0.46 0.65

Abbreviations: CAG = coronary angiography, LBBB = left bundle-branch block, NP = not performed, S/L = septum/lateral wall counts ratio, E =exercise, D = dipyridamole, (�) = normal , (+) perfusion defect.

Clin. Cardiol. Vol. 26, April 2003184

routine treadmill exercise with modified Bruce protocol (n:18LBBB patients, n:3 normal subjects) and pharmacologic stress(oral, dipyridamole tablet, 5 mg/kg) (n:7 LBBB patients, n:3normal subjects)20, 21 are preferred for cardiac stress. Tech-netium-99m MIBI doses were 8 mCi (296 MBq.) and 25 mCi(925 MBq.) for stress and rest SPECT imaging, respectively.Stress and rest images were obtained 45 and 60 min after in-jections, respectively. Sixty-four projections were obtained us-ing a 64 � 64 matrix for 25 and 30 s/frame for stress and restSPECT images, respectively. For both stress and rest images,routinely used Butterworth prefilter and Ramp filter were uti-lized for reconstruction and back projection, respectively.

Gated SPECT imaging: After the completion of stress-restSPECT imaging, gated SPECT images were acquired by di-vision of cardiac cycle into eight frames in all patients andcontrol subjects. No new doses of 99mTc MIBI were reinject-ed for gated SPECT imaging because gated SPECT imagingwas started immediately after completion of rest myocardialSPECT imaging in all patients and control subjects. Thirty-two projections (40 s each) were obtained from right anterioroblique to left posterior oblique projections over 180˚. GatedSPECT image reconstruction was carried out by using GEMultitomo (GE Medical Systems, Twinsburg, Ohio, USA)protocol. Hann prefilters with cut-off frequency of 0.7 cycles/cm and Ramp filter were used for prefiltering stages. AllSPECT and gated SPECT studies were acquired on a dual-head gamma camera (Starcam 4000i Optima, GE MedicalSystems, Milwaukee, Wisc., USA) equipped with a low-ener-gy, high-resolution collimator.

Image Interpretation and Quantitative Analysis

A gated end-diastolic SPECT slice was derived from thedata of the first frame. Reconstructed gated SPECT short-axis images were displayed on screen to determine the end-systolic slice, which has the smallest cavity (often fourth orfifth frame).

Both stress and rest SPECT and gated end-diastolic andend-systolic SPECT images were assessed visually and quan-titatively. Visual evaluation was carried out on short-axis, ver-tical long-axis, and horizontal long-axis slices on SPECT im-ages and the corresponding slices on gated end-diastolic andend-systolic SPECT images. The perfusion pattern of eachmyocardial segment was described as “normal,” “reversibleperfusion defect,” or “irreversible perfusion defect.”

The quantitative analysis was performed by placing a 2 � 2pixel-size small box of region of interest (ROI) on the inter-ventricular septum and lateral wall on short-axis slices ofstress and rest SPECT and gated end-diastolic and end-sys-tolic SPECT images. Using the mean counts in these ROIs,septum to lateral wall ratio (S/L) was calculated. Furthermore,the count increase from end-diastole to end-systole in septumand lateral wall were calculated using the formula of the S/Lratio difference (end-systolic S/L ratio � end-diastolic S/L ra-tio) for control subjects and patients with LBBB.

Coronary angiography: Selective left and right coronaryangiograms were obtained by Judkins approach. Lesions were

considered significant if they exceeded 50% of the lumen di-ameter in two projections.

Statistical Analysis

All values are expressed as mean ± standard deviation (SD).Septum to lateral wall ratios of patients with LBBB and con-trol subjects were compared using the Mann-Whitney U test,and S/L ratios of LBBB patients were compared using thepaired-samples t-test.

Results

Stress-Rest Myocardial Perfusion SPECT

Stress-rest SPECT imaging was normal for all control sub-jects ( 6/6, 100%) and 5 of 25 patients (20%). Of 25 patients,11 (44%) and 9 (36%) had reversible and irreversible perfu-sion defect on septal wall, respectively (Fig. 1). Of 20 patientswho had perfusion defects (reversible or irreversible) onstress-rest SPECT images, 12 had normal coronary arteries onCAG (Table I and Figs. 2, 3).

Gated SPECT Imaging

End-systolic images were normal in all control subjects(100%) and in 7 of 25 patients (28%). Of 25 (72%) patientswith LBBB, 18 had defects on septal wall (Fig. 1). Of the 18patients with LBBB, 11 had normal coronary arteries on an-giography (Table I). End-diastolic images were normal in allcontrol subjects (100%) and in 20 of 25 (80%) patients withLBBB: only 5 of 25 (20%) patients with LBBB had perfusiondefects on septal wall (Fig. 1). Three of five patients withLBBB had normal coronaries on CAG (CAG could not beperformed in two of these five patients) (Table I and Figs. 2, 3).

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FIG. 1 Comparison of the results obtained from visual assessmentof stress-rest (nongated) SPECT and gated SPECT images in pa-tients with left bundle-branch block.

H. Demir et al.: Tc-99 MIBI-gated SPECT in patients with LBBB 185

Coronary Angiography

Coronary angiography was performed in 15 patients withLBBB and in all 6 controls subjects, all of whom had angio-graphically normal coronary arteries (Fig. 4).

Quantitative Analysis of Nongated and Gated SPECT Images

Cumulative results of septum/lateral wall count ratios forstress, rest, and end-diastolic and end-systolic images are illus-trated in Table I. The mean S/L ratios obtained from stress andrest SPECT slices in patients with LBBB are 0.73 ± 0.11 and0.77 ± 0.10, respectively. Corresponding figures for end-sys-tolic and end-diastolic gated SPECT slices are 0.66 ± 0.16 and

0.86 ± 0.19, respectively (Fig. 2). The ratios of the patientswith LBBB and the control subjects revealed no statisticallysignificant difference between end-diastolic values (0.86 ±0.19 in LBBB vs. 0.98 ± 0.15 in normal subjects, p > 0.05).However, significant differences were observed between end-systolic, stress, and rest values in the control subjects and in pa-tients with LBBB (p<0.001) (Fig. 2). The S/L ratio difference(end-systolic S/L ratio � end-diastolic S/L ratio) in normalsubjects was �0.03; the corresponding figure in patients withLBBB was �0.22. An example of a patient who had septal ir-reversible perfusion defect in stress-rest myocardial perfusionSPECT but normal end-diastolic gated SPECT images wasdemonstrated in Figure 5.

Results of Comparison of Stress Methods

Fisher’s exact test revealed no significant difference in re-sults with respect to stress methods (treadmill exercise vs.dipyridamole): in patients with LBBB the two-tailed p valueswere 0.436, 0.399, 0.663, and 0.289 for stress SPECT, restSPECT, gated end-systolic and gated end-diastolic SPECTimages, respectively.

Discussion

Despite sufficient perfusion, defects can be seen in septumon nongated SPECT images if they do not show a count in-crease from end-diastole to end-systole as a result of segmen-tal contraction abnormality.22 Septal perfusion defects aretherefore common on nongated SPECT slices in patients withLBBB, even in the absence of coronary artery disease.

False positive defects are seen both on 201Tl and 99mTc-MIBI images excluding any radiopharmaceutically relatedcause.2–13, 23 The etiology of false positive results is yet to befully understood. Small-vessel disease, decreased coronary

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FIG. 4 Comparison of coronary angiography results of patients withleft bundle-branch block who had abnormal perfusion on stress-rest(nongated) SPECT and gated SPECT imaging. Abbreviations as inFigure 3.

FIG. 3 Comparison of coronary angiography results of patientswith left bundle-branch block who had normal perfusion on stress-rest (nongated) SPECT and gated SPECT imaging. CAG = coronaryangiography, NP = not performed.

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FIG. 2 Comparison of the results of quantitative assessment ofstress-rest (nongated) SPECT and gated SPECT studies in patientswith left bundle-branch block and in the control group. S/L =Septum to lateral wall, LBBB = left bundle-branch block.

Clin. Cardiol. Vol. 26, April 2003186

flow reserve, a shortened diastolic filling time, and thinnedseptum as part of a cardiomyopathic process had been sug-gested to explain the possible mechanism for false positiveseptal perfusion defects.1, 3, 6, 10, 11, 14, 24–26

Gated SPECT imaging was recommended to avoid the ef-fects of wall motion abnormalities on gamma camera imagingby separately recording end-systolic and end-diastolic counts.1

Gated myocardial SPECT slices represent serial frames of acardiac cycle. Count increase from end-diastole to end-systoleon gated SPECT slices corresponds to the degree of wall thick-ening.27 This technique thus allows for assessing wall thicken-ing by comparing end-systolic and end-diastolic images.

The real challenge stems from false positive septal perfusionabnormalities seen in SPECT imaging following pharmaco-logic or physical stress in daily clinical practice. Thus, compar-ison should be made between nongated stress-rest (or vice versa) SPECT slices and gated rest end-systolic and end-dias-tolic slices. We therefore performed our comparison in a realclinical setting: we compared the routinely performed stress-rest (nongated) myocardial perfusion SPECT with gated restSPECT on the same patients in the same imaging session.

On stress-rest nongated SPECT images we found that 80%of patients with LBBB had perfusion defects in the septum,but the corresponding figures for end-systolic gated sliceswere 72%, and for gated end-diastolic slices only 20%. Thecount increase from end-diastole to end-systole in the septumwas smaller than that in the lateral wall. The greater differencein patients with LBBB indicates smaller count increase due toreduced wall thickening in the septum, which might cause hy-poperfusion seen in SPECT images in patients with LBBB.

Type of cardiac stress was suggested to have a role in this re-sult; pharmacologic stress, particularly dipyridamole-inducedstress, was recommended to avoid false positive perfusion ab-normalities. In our study, we employed both treadmill exerciseand dipyridamole stress protocols according to the patients’needs and eliminated the effect of stress type on the results by

studying statistically all results (nongated stress, nongated rest,gated end-systolic and gated end-diastolic SPECT slices in pa-tients with LBBB): there was no statistically significant differ-ence in the results with respect to the stress type. Pharmaco-logic stress did not prove to be a real clinical solution becausewall motion abnormality in LBBB was still a problem evenunder pharmacologic stress conditions.19–21

Study Limitations and Future Recommendations

In this study, the number of normal subjects was smallerthan the number of patients with LBBB (6 vs. 25). Althoughstatistically our study is validated and correct, a higher numberof normal subjects could have made a more reliable conclu-sion possible by optimizing comparative analysis of the resultsof normal subjects and patients.

Conclusion

We conclude that impaired septal wall thickening could re-sult in false positive septal perfusion defects, and gatedSPECT technique, especially end-diastolic images, can avoidfalse positive septal perfusion defects.

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