Influence of Methodology on the Presence and Extent of Mismatching

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However, methodological factors can influence assess ment of the presence of mismatching because of differences in background activity between the tracers.
CLINICAL INVESTIGATIONS

Influence of Methodology on the Presence and Extent of Mismatching Between 99mTc-MIBIand 123I-BMIPP in Myocardial Viability Studies André A. Dobbeleir, Anne-Sophie E. Hambye and Philippe R. Franken Department of Nuclear Medicine, Middelheim Hospital, Ant\verp, and Department of Nuclear Medicine, Free University of Brussels, Brussels, Belgium Key Words: 123l-beta-methyl-p-iodophenyl-pentadecanoic acid; chronic ischemie myocardium; myocardial viability; quantification Discordant uptake (mismatching) of 123l-labeledbeta-methyl-piodophenyl-pentadecanoic acid (BMIPP) less than 99mTc-labeled J NucÃ-Med 1999; 40:707-714 methoxyisobutyl isonitrile (MIBI) is a good predictor of myocardial viability. However, methodological factors can influence assess ment of the presence of mismatching because of differences in background activity between the tracers. In this study, we .Ithough a normal uptake of 99mTc-labeledmethoxyiso investigated the influence of methodological parameters on the butyl isonitrile (MIBI) is a good predictor of functional mismatching between BMIPP and MIBI in patients with chronic ischemie heart disease. Methods: Polar maps were created to recovery of myocardial tissue, a decreased uptake clearly quantify the extent of mismatched tissue measured in 10 patients underestimates its viability (/). Furthermore, the lower limit with myocardial infarction according to three methods for data of normal uptake of this tracer is not precisely defined and processing: no correction, subtraction of background activity fluctuates between 50% and 60% (2,3). measured in the left ventricle cavity and dual-window scatter Because of an early metabolic switch from ß-oxidation to correction. Mismatching was expressed as a percentage of the glycolysis to preserve the production of high-energy phos surface of the left ventricle globally as well as for each arterial territory using a BMIPP uptake of at least 10% less than MIBI as phates in hypoxic myocardium, SPECT with radioiodinated the threshold. The results of dobutamine stress echocardiografree fatty acid analogs has been proposed as an alternative to phy and the evolution of the regional contractility at 6-mo [18F]fluorodeoxyglucose for imaging cardiac metabolism follow-up were used as references. Results: Mean background (4). In this setting, mismatching with fatty acid uptake more activity in the ventricle cavity was 9.3% of the maximum activity severely reduced than flow is assumed to correspond to for MIBI and 21.4% for BMIPP before, and 2.8% and 8.3% after jeopardized but viable myocardium (4-7). scatter correction. Fourteen arterial vascular territories demon strated baseline wall-motion abnormalities; 9 territories showed However, comparing the tissue uptake of radiopharmaceucontractile reserve with dobutamine stress echocardiography. ticals labeled with different isotopes requires special atten Significant mismatching was found in 5 of 14 regions without tion to acquisition parameters. In particular, the use of correction, 9 of 14 after scatter correction and 13 of 14 after I23l-labeledcompounds can lead to an underestimation of background subtraction. Compared with the evolution of resting the defect contrast because of the emission of 2.5% of the regional contractility at follow-up, optimal results were found high-energy photons (440-625 keV). In low-energy collimawhen using the scarier-corrected data. Without correction, mis matching between BMIPP and MIBI was partially disguised tors, these photons cause septal penetration and scatter, because of the higher noise level in the iodine images. On the which is, in part, detected in the 159-keV photopeak contrary, subtraction of background measured by means of a window. This phenomenon results in an increased back single region of interest overestimated the magnitude of mismatch ground level in the 123Iimage. This can partly or completely ing due to the heterogeneous background distribution in the ventricular cavity. Conclusion: In quantifying the presence and disguise the reduction in fatty acid uptake related to the perfusion tracer or even result in an increased fatty acid/ extent of mismatching between MIBI and BMIPP in chronic ischemie heart disease, significant differences in the detection of perfusion uptake, as recently reported by Sloof et al. (8) in viability are noted according to the acquisition and processing chronic ischemie heart disease. One approach to over methods used. Scatter correction of the acquisition data is the coming this problem in performing I23l-imaging is to use most accurate and reliable method for identifying viable myocar medium-energy instead of low-energy collimators, despite a dium. Received Apr. 27, 1998; revision accepted Sep. 18, 1998. For correspondence or reprints contact: AndréDobbeleir, MSc, Nuclear Medicine, Middelheim Hospital, Lindendreef 1,2020 Antwerp, Belgium.

certain loss of resolution (9). Alternatively, low-energy high-resolution collimators can be used, even for quantita tive 123ISPECT imaging, if a scatter correction is applied (10).

METHODOLOGICAL PROBLEMS IN FREEFATTYACIDSCINTIGRAPHY • Dobbeleir et al.

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This study aimed at clarifying the influence of methodol ogy on the quantitative assessment of mismatching between I23l-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) and MIBI. For this purpose, we quantified the presence and degree of mismatching in 10 patients with previous transmural myocardial infarction using different methodological approaches and a previously described quantitative method (11). We compared the results with those of dobutamine stress echocardiography. We used all-purpose, low-energy collimatore instead of high-resolution collimators because, although the amount of septal penetration is similar with both kinds of low-energy collimators for I23l-labeled com pounds, the photopeak sensitivity is higher with all-purpose collimators, resulting in significant improvement in the signal-to-noise ratio. MATERIALS AND METHODS Study Design Ten patients with previous transmural myocardial infarction (median 3 mo, range 1 mo-10 y) were studied. Within 1 wk, coronary angiography, dobutamine stress echocardiography, radionuclide angiography, BMIPP and MIBI studies were obtained (the last two with a 3-d interval). The left ventricle was divided by echocardiography into eight segments. The anterobasal, anterolateral and anteroseptal segments were ascribed to the left anterior descending artery (LAD); the posterolateral to the left circumflex artery (LCX); and the diaphrag matic, posteroseptal and posterobasal to the right coronary artery (RCA). The apex was attributed to the LAD unless a dominant RCA or LCX was reported. In each arterial territory, wall motion was analyzed at rest and during intravenous infusion of 5 and 10 (jg/kg/min dobutamine and was graded as normal, slightly, mildly or severely hypokinetic, akinetic or dyskinetic. Viability was defined as an increase in wall motion of at least one grade in a segment with resting abnormalities. After completion of the tests, revascularization was performed within 1 mo in 6 patients in whom it was technically feasible; the remaining patients were conservatively treated. Follow-up data were obtained 6-7.5 mo later. All patients received written information about the study and gave informed consent. The study protocol had been approved by the Commission of Medical Ethics of the Hospitals of Antwerp.

Resting MIBI SPECT was started at a mean time of 80 min postinjection of 925 MBq (25 mCi) using a similar protocol as for the BMIPP but with 40-s acquisition time per projection and different photo- and scatterpeak characteristics. (The photopeak was set at 140 keV with a window between 126 and 154 keV; the scatter window was between 100 and 125 keV.) Determination of k Fraction for Dual-Window Scatter Correction In SPECT, scatter compensation consists of subtracting a fraction, k, of the compton image, C(x,y), from the photopeak image, P(x,y), to obtain a scatter-compensated image, I(x,y): I(x,y) = P(x,y) - k X C(x,y). The value of k depends on the acquisition geometry, the energy resolution of the camera, the energy settings and the size of the object (14). Using the above-mentioned collimators and energy window settings, the projection version of the dual-window scatter correc tion was implemented by performing weighted subtractions with an experimentally determined k value directly on the projection images before reconstruction (15). Experimental determination of this k value was performed as follows. Using the same window settings and collimators that would be used for the patient studies, the scatter subtraction fraction was calculated for "mTc and 123Iand different source geometries. Scatter correction was performed on planar images because SPECT data consist of a set of planar images and quantitative distortions will propagate in the tomographic studies. The following source geometries were tested for both isotopes: (a) a small point source, (b) a cylinder of 5-cm diameter and 1-cm thickness, (c) a cylinder of 10-cm diameter and 2-cm thickness and (d) a large cylinder of 10-cm diameter and 10-cm thickness. Images were acquired in air and with increasing depths of attenuating medium—4, 8, 12, 16 and 20 cm of water. When the logarithm of the counts was plotted against depth, the resulting straight line had a slope equal to the attenuation coeffi cient for broad-beam geometry, and after the accurate elimination of scatter, the absorption coefficient for narrow-beam geometry (16). Therefore, k was iteratively changed for each source, and the subsequent scatter-corrected counts were fitted to the single monoexponential function up until the attenuation coefficient corresponded to the values for water for the two isotopes (0.15 cm-' for "mTc and 0.146 cm-' for 123I).

Scintigraphic Imaging Protocol Radioiodination of BMIPP was realized at the Free University of Brussels using I23I(p,5n) and the Cu(I)-assisted isotopie exchange

Processing and Analysis of Scintigraphic Data The extent of viable tissue was evaluated with the following reaction developed by Mertens et al. (12). types of processing: (a) without correction; (b) after background BMIPP was intravenously injected into resting patients at a subtraction [a 1-cm2 region of interest (ROI) was drawn at the basal part of a 1-cm-thick midventricular long-axis slice on both MIBI mean dose of 159 MBq (4.3 mCi) after at least 6 h of fasting. and BMIPP images; the activity measured within these ROIs was Potassium perchlorate was administered to the patients 15 min subtracted from the data before bull's-eyes were created]; (c) using before injection to block thyroidal uptake of free iodine. SPECT dual-window scatter correction with k values of 0.7 for 99mTcand was started 30 min postinjection using a triple-head gamma camera 1.0 for 123I;and (d) using dual-window scatter correction but a (Triad; Trionix Lab. Twinsburg, OH), detector size 40 X 20 cm, subtraction constant k = 1.3 instead of 1.0 for 123I.These values of equipped with all-purpose, low-energy collimators. Ninety projec tions (30 per head) of 60-s duration were acquired over a 360° k for I23I, corresponding respectively to the point source and the phantom of 10-cm diameter and 10-cm height, had been found to noncircular body contour orbit, using a 128 X 64 matrix. A scatter image was obtained in a second window slightly less than the be the minimum and maximum correction fractions in the experi photopeak according to the method of Jaszczak et al. (13). The mental measurements. photopeak image was set at 159 keV with a window between 143 The three standard orthogonal tomograms were obtained after and 175 keV. The scatter image was acquired at 116-142 keV. filtered backprojection and appropriate reorientation of the images

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THE JOURNALOF NUCLEARMEDICINE• Vol. 40 • No. 5 • May 1999

using a Butterworth prefilter (cutoff frequency 0.75 cycles/s for MIBI and 0.6 cycles/s for BMIPP, order 5) and a ramp filterbackprojection filter, and polar maps were created. Quantification of Mismatching Color-coded polar maps allowing quantitative analysis of the relative proportions of normal, viable and scar tissue for the left ventricle globally and for each arterial territory were created as described (11). By quantifying the magnitude of viable tissue measured by the four processing methods, the influence of methodology on the quantitative assessment of mismatching be tween BMIPP and MIBI could be evaluated. These polar maps comparing the MIBI and BMIPP images were obtained as follows: The lower limit of normal MIBI uptake was defined as 60% of the normal local value (2) and was represented by red; scar tissue, defined as MIBI uptake