Feasibility of in vivo dual-energy myocardial SPECT for monitoring the distribution of transplanted cells in relation to the infarction site

Purpose Cell therapy using bone marrow mesenchymal stem cells (BMSCs) shows promise in the treatment of myocardial infarction (MI) but accurate cell delivery within MI areas remains critical. In the present study, we tested the feasibility of in vivo pinhole SPECT imaging for monitoring the sites of intramyocardial implanted BMSCs in relation to targeted MI areas in rats.Methods BMSCs were labelled with ¹¹¹In-oxine and injected within the fibrotic areas of 3-month-old MI in ten rats. Two days later, dual ¹¹¹In/^99mTc-sestamibi pinhole SPECT was recorded for localisation of ¹¹¹In-BMSCs on a 15-segment left ventricular (LV) division. Additional ^99mTc-sestamibi pinhole SPECT had been performed 1 month earlier and on the day before transplantation. In vitro counting on histological sections was used to validate the pinhole SPECT determination of ¹¹¹In-BMSC activity within LV segments.Results The underperfused MI area (segments with <70% uptake) was stable between the ^99mTc-sestamibi SPECT study recorded at 1 month (4.6±1.9 segments) and at 1 day (4.7±2.3 segments) before transplantation. ¹¹¹In-BMSCs were detected by dual-energy SPECT in 56 segments: 33 (59%) were underperfused MI segments but 23 (41%) were not (14 adjacent and nine remote segments). Finally, ¹¹¹In-labelled BMSCs were not detected in 14 out of the 47 (30%) underperfused MI segments.Conclusion When BMSCs are injected within MI areas in rats, sites of early cell retention do not always match the targeted MI areas. The dual-energy pinhole SPECT technique may be used for monitoring the sites of early retention of implanted BMSCs and the data obtained may have critical importance when analysing the effects of cardiac cell therapy.     

Simultaneous assessment of Tc-99m-sestamibi and I-123-BMIPP myocardial distribution in patients with myocardial infarction: Evaluation of left ventricular function with ECG-gated myocardial SPECT

123I-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) is a branched-chain free fatty acid that is used to evaluate various cardiac diseases. The aim of the present study was to investigate the relationship between myocardial perfusion (99mTc-sestamibi) and BMIPP uptake, and to correlate perfusion and metabolic alterations with regional left ventricular dysfunction in patients with myocardial infarction (MI). ECG-gated dual-isotope myocardial SPECT was performed on 130 patients with MI with sestamibi (555 MBq) and BMIPP (148 MBq). The patients were classified into 3 groups according to PTCA therapy and the interval between the onset of infarction and RI injection (OR time). Group A (n = 56) included patients whose OR time was less than one month and who had undergone successful PTCA, Group B (n = 36) had OR times of less than one month and had conservative medical therapy, and Group C (n = 38) had OR times of over one month. The severity scores of the dual-isotope images were calculated from the defect scores in 9 segments. From the ECG-gated SPECT data with sestamibi, the left ventricular ejection fraction (LVEF; %) and regional wall motion were determined automatically using the QGS program LVEF obtained from gated SPECT correlated well with the severity scores for sestamibi and BMIPP (r = -0.68 and -0.76, respectively). The delta severity scores (BMIPP scores - sestamibi scores) of Group A were significantly higher than those of the other two groups (3.6 +/- 3.0 vs. 1.5 +/- 1.7 and 1.0 +/- 1.4, p < 0.001 ). The rate of dysfunctional segments with normal sestamihi distribution was significantly higher in Group A than in Group C (20.7% vs. 6.7%, p < 0.001). ECG-gated dual-isotope SPECT is useful since myocardial perfusion, fatty acid metabolism and left ventricular function can be analyzed during a single examination, so that this procedure has the potential to provide comprehensive information when evaluating patients with ischemic heart disease.     

Influence of infarct-zone viability detected by rest Tc-99m sestamibi gated SPECT on left ventricular remodeling after acute myocardial infarction treated by percutaneous transluminal coronary angioplasty in the acute phase

BACKGROUND: The purpose of this study was to assess the value of technetium 99m sestamibi gated single photon emission computed tomography (SPECT) in predicting the evolution of left ventricular volumes in patients treated successfully in the acute phase of a myocardial infarction (MI). METHODS AND RESULTS: Twenty-nine patients with acute MI and early percutaneous transluminal coronary angioplasty (PTCA) were included in this study. A rest Tc-99m sestamibi electrocardiography (ECG)-gated SPECT study was performed 21 +/- 5 days after PTCA. The myocardial perfusion index was calculated by use of a semiautomatic sectorial analysis. All patients had contrast ventriculography performed during the acute phase and 6 months later. The patients were separated into two groups according to the absence (group I, n = 21) or presence (group II, n = 8) of end-systolic enlargement. The perfusion index in the infarct sectors was -2.29 +/- 2.90 SD in group I and -6.40 +/- 2.85 SD in group II ( P < .01). With a cutoff value of -2.46 SD, the sensitivity and specificity of Tc-99m sestamibi SPECT for the prediction of end-systolic volume enlargement were 100% and 62%, respectively. When the functional data from ECG-gated acquisitions were added, specificity increased to 86%. CONCLUSIONS: Despite successful PTCA in the acute phase of MI, an increase in end-systolic volume was observed at 6 months in 28% of patients. Tc-99m sestamibi ECG-gated SPECT performed 3 weeks after the acute phase could predict this enlargement with a high accuracy.     

Selective intracoronary injection of sestamibi to detect myocardial viability: Prediction of perfusion and contractile recovery after percutaneous transluminal coronary angioplasty

BACKGROUND: The main limitation of myocardial single photon emission computed tomography (SPECT) in detecting hibernating myocardium is the poor delivery of radiotracers in hypoperfused areas supplied by severely stenotic coronary arteries. Increasing local availability of radiotracers by intracoronary injection might represent an attractive solution. The hypothesis that the intracoronary administration of sestamibi could improve myocardial SPECT accuracy in detecting hibernating myocardium was addressed in this pilot study. METHODS AND RESULTS: Seven patients with prior myocardial infarction and severe stenosis of the infarct-related artery underwent myocardial SPECT after intracoronary injection of technetium 99m sestamibi immediately before percutaneous transluminal coronary angioplasty (PTCA). Wall motion and perfusion were evaluated, before and 1 month after PTCA, by 2-dimensional echocardiography and rest-redistribution thallium 201 SPECT. A "low-flow area" was identified on the pre-PTCA Tl-201 SPECT image as the area with less than 50% of maximum radiotracer uptake. Changes in wall motion and perfusion in the low-flow area were compared with results of intracoronary sestamibi imaging. On a pixel-by-pixel analysis, intracoronary sestamibi predicted perfusion recovery within the low-flow area with a 91% sensitivity, a 78% specificity, and an 82% overall accuracy. Only in the 5 patients with an extent of sestamibi uptake greater than one third of the low-flow area was an improved regional and global left ventricular wall motion observed after PTCA (wall motion score index decreased from 1.95 +/- 0.28 to 1.60 +/- 0.34, P =.007; left ventricular ejection fraction increased from 42% +/- 7% to 49% +/- 7%, P =.001; asynergic segments in the low-flow area decreased from 3.6 +/- 0.9 to 1.8 +/- 1.5, P =.021). CONCLUSIONS: In patients with prior myocardial infarction and severe stenosis of the infarct-related artery, sestamibi uptake after intracoronary administration identified viable myocardium that was undetected after rest-redistribution thallium SPECT but capable of clinically significant contractile improvement after revascularization.     

Nitrate-enhanced gated SPECT in patients with primary angioplasty for acute myocardial infarction: evidence of a reversible and nitrate-sensitive impairment of myocardial perfusion

Purpose Reperfusion of myocardial infarction (MI) leads to a reversible dysfunction of coronary vessels. We hypothesised that vasodilating drugs such as nitrates might improve sestamibi uptake within viable areas of recently reperfused MI, thereby enhancing prediction of subsequent improvements in perfusion and contractility. This study was aimed at assessing nitrate-enhanced sestamibi gated SPECT after MI reperfusion. Methods Twenty-nine patients underwent rest followed by nitrate sestamibi gated SPECT at 9 ± 3 days after primary angioplasty for acute MI and at follow-up, 4–10 months later. Four MBq/kg of ^99mTc-sestamibi was injected at rest, and 12 MBq/kg after nitroglycerin spray. Results Follow-up improvements were documented for both perfusion (P+) and contractility (C+) in 18% of the 180 initially abnormal segments, in neither perfusion (P−) nor contractility (C−) in 44%, in contractility only (C+P−) in 16% and in perfusion only (C−P+) in 22%. Perfusion improvement was related to lower sestamibi uptake on baseline rest SPECT (P+: 42 ± 15% vs P−: 50 ± 15%, p = 0.001) and, moreover, to a higher increase between rest and nitrate uptake (P+: +9.5 ± 6.5% vs P−: +2.0 ± 5.9%, p < 0.001). Contractility improvement was related to sestamibi uptake on baseline nitrate SPECT (C+: 58 ± 15% vs C−: 38 ± 16%, p < 0.001), a variable enhancing the prediction provided by sestamibi uptake at rest (p < 0.05). Conclusion The improvement in perfusion which is documented in the months following MI reperfusion is predicted by initial nitrate enhancement of sestamibi uptake, suggesting a mechanism of reversible vascular injury. In this particular setting, sestamibi uptake is a better predictor of contractility recovery when determined after nitrate administration rather than under conventional resting conditions.     

In vivo detection of stem cells grafted in infarcted rat myocardium.

The evaluation of stem cell-mediated cardiomyoplasty by noninvasive in vivo imaging is critical for its clinical application. We hypothesized that dual-tracer small-animal SPECT would allow simultaneous imaging of (99m)Tc-sestamibi to assess myocardial perfusion and of (111)In-labeled stem cells to delineate stem cell engraftment. METHODS: Three to 4 million rat embryonic cardiomyoblasts (H9c2 cells) were labeled with 11.1-14.8 MBq (0.3-0.4 mCi) of (111)In-oxyquinoline and then injected into the border zones of infarcted myocardium of rats. (111)In images were acquired with a SPECT scanner 2, 24, 48, 72, and 96 h after the stem cells were injected into the infarcted myocardium. To visualize the perfusion deficit in the infarcted myocardium, we injected 74 MBq (2 mCi) of (99m)Tc-sestamibi (Cardiolite) intravenously 48 h after grafting. Dual-isotope pinhole SPECT was used to image (99m)Tc-sestamibi uptake simultaneously with (111)In to delineate retention of (111)In-labeled stem cells. The presence of labeled stem cells was confirmed by autoradiography and histology. RESULTS: SPECT of (99m)Tc-sestamibi was used to delineate perfusion deficits and infarcted myocardium. Bull's-eye plots indicated that the (111)In signal from the labeled stem cells overlapped the perfusion deficits identified from the (99m)Tc-sestamibi images. The (111)In signal associated with the radiolabeled stem cells could be detected with SPECT of the heart for 96 h after engraftment. CONCLUSION: This study demonstrated the feasibility of using dual-isotope pinhole SPECT for high-resolution detection of perfusion deficits with (99m)Tc-sestamibi and with (111)In-labeled stem cells grafted into the region of the infarct.     

In vivo tracking of 111In-labeled bone marrow mesenchymal stem cells in acute brain trauma model

IntroductionThis study was to evaluate the in vivo distribution of intravenously transplanted bone marrow-derived mesenchymal stem cells (BMSCs) in an acute brain trauma model by ¹¹¹In-tropolone labeling.MethodsRat BMSCs were labeled with 37 MBq ¹¹¹In-tropolone. Their labeling efficiency and in vitro retention rate were measured. The viability and proliferation of labeled BMSCs were evaluated for 14 days after labeling. The biodistribution of ¹¹¹In-labeled BMSCs in trauma models was compared with those of sham-operated rats and normal rats on gamma camera images. The migration of ¹¹¹In-BMSCs to the traumatic brain was evaluated using confocal microscope.ResultsThe labeling efficiency of ¹¹¹In-BMSCs was 66±5%, and their retention rate was 85.3% at 1 h after labeling. There was no difference in the number of viable cells between ¹¹¹In-BMSCs and controls at 48 h after labeling. However, the proliferation of ¹¹¹In-BMSCs was inhibited after the third day of labeling, and it did not reach confluency. On gamma camera images, most of the ¹¹¹In-BMSCs uptake was observed in the liver and spleen at the second day of injection. The brain uptake of ¹¹¹In-BMSCs was detected prominently in trauma models (1.4%) than in sham-operated (0.5%) or normal rats (0.3%). Radiolabeled BMSCs were observed at the traumatic brain on the confocal microscope as they have a homing capacity, although its proliferation capacity was suppressed.ConclusionAlthough growth inhibition by ¹¹¹In-labeling need to be evaluated further prior to use in humans, ¹¹¹In-labeled BMSCs are useful for the tracking of intravenously transplanted mesenchymal stem cells in brain disease models.     

Focal pulmonary uptake during Tc-99m myocardial perfusion SPECT imaging

PURPOSE: To evaluate the incidence and origin of abnormal focal pulmonary uptake during myocardial perfusion SPECT imaging (MSPECT). METHODS: For evaluation of chest pain, 790 men and 581 women (mean age, 56 +/- 13 years) underwent MSPECT. All of them received adenosine for pharmacologic stress and Tc-99m tetrofosmin (TF, n = 817) or Tc-99m sestamibi (MIBI, n = 554) for myocardial perfusion imaging. RESULTS: Review of chest radiography with or without computed tomography revealed 111 (8.1%) focal pulmonary diseases. Among them, 38 (34.2%) showed focal pulmonary uptake (TF, 22; MIBI, 16); 27 (30.7%) of 88 showed previous pulmonary tuberculosis; 2 of 10 (20%) benign pulmonary nodules; 4 of 5 (80%) metastatic lung cancers; 2 of 4 (50%) primary lung cancers; and 3 of 4 (75%) pneumonias. No difference in uptake was noted for the two imaging agents. Intensity of uptake did not vary with origin of the uptake. Focal abnormal pulmonary uptake was found in 2.8% of patients undergoing MSPECT and in 34.2% of patients in whom radiological examinations showed regional pulmonary disease. In patients with abnormal pulmonary uptake on MSPECT, 16% had a malignant lesion, whereas 75% of patients with a pulmonary nodule shown on radiography and focal pulmonary uptake on MSPECT had a malignant lesion. CONCLUSIONS: Although the incidence of abnormal pulmonary uptake during MSPECT was very low, the incidence of malignant lesions in the patients with nodular pulmonary uptake was relatively high.     

Irbesartan has a masking effect on dipyridamole stress induced myocardial perfusion defects

BACKGROUND AND AIM: The angiotensin II type 1 (AT1) receptor antagonist irbesartan is used for the treatment of hypertension, but its anti-ischaemic effect is not yet known. Our aim was to assess the effect of irbesartan administration on the diagnostic yield of 99mTc sestamibi single photon emission computed tomography (SPECT) in patients with coronary artery disease (CAD) after dipyridamole stress. METHODS: Our study group consisted of 13 patients (11 men and two women; mean age, 53.3 +/- 10.6 years; body mass index, 26.9 +/- 3.3 kg x m(-2)) with angiographically documented CAD. All patients underwent SmTc sestamibi SPECT studies at rest, before (STRESS-1) and 2 weeks after irbesartan (150 mg daily) administration (STRESS-2) at dipyridamole stress. The extent and severity of defects were analysed by using visual and quantitative 99mTc sestamibi SPECT. RESULTS: The mean summed stress score was significantly higher during the STRESS-1 study than the STRESS-2 study (13.2 +/- 7.4 vs. 11 +/- 7.4, P=0.003). The mean size of perfusion defects at stress was significantly larger for the STRESS-1 group than the STRESS-2 group (17.8% +/- 2.85% vs. 15.3% +/- 2.95%, P=0.01). CONCLUSION: Our study showed that the AT1 receptor blocker irbesartan reduces the extent and severity of 99mTc sestamibi perfusion defects after dipyridamole stress in patients with CAD. Irbesartan may alter coronary blood flow reserve. The continued use of irbesartan before stress myocardial perfusion SPECT has a masking effect on stress induced myocardial perfusion defects. For this reason AT1 receptor blockers must be stopped before stress myocardial perfusion scintigraphic examinations.     

Detecting myocardial salvage after primary PTCA: early myocardial contrast echocardiography versus delayed sestamibi perfusion imaging.

The extent of myocardial salvage after primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) is variable and cannot be predicted on the basis of either vessel patency or early regional wall motion assessment. The aim of this study was to evaluate the reliability of microvascular integrity, as shown by myocardial contrast echocardiography (MCE), as an indicator of tissue salvage and a predictor of late functional recovery, and to compare MCE with the quantification of tracer activity in sestamibi perfusion imaging. METHODS: Twenty-six patients with AMI who received successful treatment with primary PTCA were examined with MCE during cardiac catheterization immediately before and after vessel recanalization. Myocardial contrast effect was scored as 0 (absent), 0.5 (partial) or 1 (normal). Wall motion was assessed by two-dimensional echocardiography on admission and 1 mo later with a 16-segment model and 4-point score. Resting sestamibi SPECT was collected within 1 wk after AMI. The risk area was defined by MCE as the sum of the segments with no perfusion (score 0) before PTCA. Myocardial viability was defined by MCE as an increase in contrast score in the same segments after PTCA and by sestamibi SPECT as a preserved tracer activity (>60% of peak activity). The functional recovery after 1 mo detected by two-dimensional echocardiography was the reference standard for viability. RESULTS: A total of 50 segments showed perfusion defects before PTCA (risk area). Immediately after PTCA, the MCE score increased in 44 of 50 segments, whereas sestamibi SPECT showed preserved activity in 22 of 50 segments. After 1 mo, the wall motion score decreased in 22 of 50 segments (viable segments) and was unchanged in the remaining 28 segments. Thus, MCE showed a sensitivity of 91% and a specificity of 14% in detecting viable myocardium, whereas sestamibi SPECT showed a lower sensitivity (68%) but a significantly higher specificity (75%; P < 0.00001). The positive predictive values were 45% and 68% for MCE and SPECT (P < 0.005), respectively, and the negative predictive values were 67% and 71%, respectively. On a patient basis, SPECT was more specific (79% versus 21%; P < 0.01) and showed a higher overall predictive accuracy (88% versus 50%; P < 0.01) than MCE. CONCLUSION: The demonstration of microvascular integrity by MCE performed immediately after primary PTCA has a limited diagnostic value in predicting salvaged myocardium. Conversely, tracer activity quantification in resting sestamibi SPECT performed in a later stage is confirmed to be a reliable approach for recognizing myocardial stunning and predicting functional recovery.     

Nitrate-enhanced gated technetium 99m sestamibi SPECT for evaluating regional wall motion at baseline and during low-dose dobutamine infusion in patients with chronic coronary artery disease and left ventricular dysfunction: Comparison with two-dimensional echocardiography

BACKGROUND: The value of gated single photon emission computed tomography (SPECT) in the assessment of wall motion (WM) in patients with severe perfusion defects and in the evaluation of low-dose dobutamine (LDD)-induced changes is not yet established. In patients with chronic coronary artery disease who have left ventricular (LV) dysfunction, the results of nitrate-enhanced technetium 99m sestamibi (sestamibi) gated SPECT for the evaluation of resting and LDD WM were compared with those of baseline and LDD echocardiography (LDDE). METHODS AND RESULTS: Thirty-seven patients underwent echocardiography and nitrate-enhanced sestamibi gated SPECT within 1 week at rest and during LDD infusion. WM was scored from 1 (normal) to 4 (dyskinetic) by using a 16-segment model. Segments with sestamibi uptake less than 30% were considered unsuitable for WM analysis (36 of 592 segments). Echocardiography was technically unreliable in 10 of 592 segments. The precise agreement between echocardiography and gated SPECT for baseline regional WM was 68.4% (kappa = 0.54), without significant differences for the involved coronary artery territory. The agreement for +/- 1 WM scoring was 96.5% (kappa = 0.94). Contractile reserve during LDD was detected by means of echocardiography in 36% and by means of sestamibi gated SPECT in 33% of baseline asynergic segments. Agreement for detection of WM improvement in response to LDD was 74% (kappa = 0.41). The overall and +/-1 WM score agreement for LDD WM was 67.5% (kappa = 0.50) and 94.7% (kappa = 0.91), respectively. A significant correlation between echocardiography and gated SPECT was observed for both baseline (p = 0.78) and LDD (p = 0.74) WM score index. CONCLUSIONS: In patients with coronary artery disease who have LV dysfunction, nitrate-enhanced sestamibi gated SPECT allows a reliable WM evaluation, both at rest and during LDD infusion, in almost all segments and provides results in agreement with LDDE.     

Comparative performance of gated perfusion SPECT wall thickening, delayed thallium uptake, and F-18 fluorodeoxyglucose SPECT in detecting myocardial viability

To evaluate the comparative abilities of gated single photon emission computed tomography (SPECT) wall thickening, delayed thallium-201 (Tl-201) SPECT, and F-18 fluorodeoxyglucose (FDG) SPECT in detecting myocardial viability, 23 patients with previous myocardial infarction and clinically suspected viability were studied. Each patient had at least 1 extensive fixed perfusion defect on rest/stress technetium-99m sestamibi SPECT. A total of 41 major vascular territories had fixed defects. The mean (+/- 1 SD) left ventricular ejection fraction determined from gated perfusion SPECT was 26% +/- 11%. Wall thickening was assessed in a semiquantitative fashion by the regional increase in myocardial intensity during systole and was considered normal when a > or = 20% increase was observed. Tl-201 SPECT was acquired 4 hours after resting tracer injection was administered. Viability was considered present when regional defect Tl-201 count density, determined by quantitative analysis, was > 20% greater than that on the resting sestamibi scan. FDG SPECT was performed independently with a 10 mCi F-18 FDG dose after oral glucose loading was performed. A camera equipped with ultrahigh energy collimation was used. Quantitative criteria for viability were the same as for Tl-201. In the 23 patients viability within the fixed sestamibi defects was manifest by preserved wall thickening in 8 patients, delayed Tl-201 uptake in 10 patients, and FDG uptake in 18 patients. Nine major vascular territories with fixed defects were judged viable by wall thickening, 11 by Tl-201 SPECT, and 24 by FDG SPECT (P = .0009). We conclude that FDG SPECT demonstrates more evidence of myocardial viability than either gated sestamibi wall thickening or delayed Tl-201 SPECT.     

Accuracy of left ventricular ejection fraction determined by gated myocardial perfusion SPECT with Tl-201 and Tc-99m sestamibi: Comparison with first-pass radionuclide angiography

BACKGROUND: We compared estimates of left ventricular ejection fraction (LVEF) assessed by gated single photon emission computed tomography (SPECT), using both technetium-99m sestamibi and thallium-201, with those obtained by first-pass radionuclide angiography (FPRNA) in patients with a broad spectrum of LVEF and perfusion abnormalities. METHODS: Sixty-three patients were randomly selected to undergo a dual isotope gated SPECT study (rest Tl-201 followed by adenosine Tc-99m sestamibi scintigraphy). Studies were processed by use of the Cedars quantitative gated SPECT software. FPRNA was acquired during an intravenous bolus injection of Tc-99m sestamibi and processed with a commercially available software. RESULTS: The estimates of LVEF were similar (P = NS) with Tl-201 gated SPECT (54% +/- 15%), Tc-99m gated SPECT (54% +/- 16%), and FPRNA (54% +/- 12%). There was an excellent correlation between Tc-99m and Tl-201 gated SPECT (Pearson's r = 0.92, P < .0001). There were also good linear correlations between Tc-99m sestamibi gated SPECT and FPRNA (Pearson's r = 0.85, P < .0001), as well as between Tl-201 gated SPECT and FPRNA (Pearson's r = 0.84, P < .0001). In the 16 patients with LVEF < 50%, Tc-99m sestamibi gated SPECT and FPRNA (Pearson's r = 0.84, P < .0001) and Tl-201 gated SPECT and FPRNA (Pearson's r = 0.92, P < .0001) correlated well. CONCLUSION: LVEF can be accurately assessed by gated SPECT with either Tc-99m sestamibi or Tl-201 in properly selected patients with normal or depressed left ventricular function.     

Initial infarct size predicts subsequent cardiac remodeling in the rat infarct model: an in vivo serial pinhole gated SPECT study.

The rat infarct model is widely used to study left ventricular (LV) remodeling, a main cause of heart failure characterized by progressive LV dilatation. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The aim of this study was to assess this new imaging technique for predicting and quantifying variable LV remodeling from the rat infarct model. METHODS: Pinhole 99mTc-sestamibi gated SPECT was validated for determining LV volume and identifying the necrotic and nonviable LV segments (<50% of 99mTc-sestamibi uptake) in rats, and it was applied to monitor rat LV function from 48 h to 12 wk after occlusion of the left anterior descending coronary artery (LAD) (n = 20) or sham operation (n = 9). RESULTS: In LAD-occluded rats, 48-h SPECT necrosis was large (> or =30% LV) in 6, limited (<30% LV) in 6, and undetectable in 8. End-diastolic volume of LAD-occluded rats was equivalent to that of sham-operated rats at 48 h (320 +/- 84 microL vs. 293 +/- 48 microL; not significant) but became higher at 12 wk (501 +/- 191 microL vs. 343 +/- 46 microL; P = 0.01). The follow-up increase in end-diastolic volume, which reflects the remodeling process, was closely related to the initial extent of necrosis revealed by the SPECT images (P < 0.001; R2= 0.85). This increase was limited in sham-operated rats (50 +/- 15 microL) and in the LAD-occluded rats with undetectable necrosis (55 +/- 35 microL) but it was around 3- and 7-fold higher in the LAD-occluded rats with limited (165 +/- 57 microL) and large (366 +/- 113 microL) necrosis, respectively. CONCLUSION: The variable LV remodeling documented after coronary occlusion in rats closely relates to the variable extent of necrosis provided by this model. Pinhole gated SPECT allows this remodeling to be predicted and quantified and, hence, constitutes an original tool for the experiments scheduled on the rat infarct model.     

"False-positive" myocardial perfusion scintigraphy findings in patients with angiographically normal coronary arteries: insights from intravascular sonography studies.

Abnormal exercise perfusion findings have been described as false-positive for coronary artery disease in patients with suspected angina and angiographically normal coronary arteries. METHODS: The significance of this finding was further investigated by obtaining intravascular sonograms and Doppler guidewire measurements of at least 2 coronary arteries in 20 consecutive patients who had chest pain, normal coronary angiography findings, and positive stress-rest sestamibi SPECT findings. The summed reversible score was used to describe the extent and severity of reversible perfusion defects. On the basis of scintigraphy findings, vessels were grouped as supplying underperfused myocardial segments (target vessels, n = 20) or normal territories (reference vessels, n = 25). The presence and extension of atherosclerotic disease of the epicardial arteries were assessed by intracoronary sonography. Measurements of plaque area (PA), vessel area (VA), and relative cross-sectional PA (RPA) (RPA = PA/VA) were obtained at the site of maximum plaque concentration. The coronary flow velocity reserve (CFR) was assessed during adenosine-induced hyperemia, and the relative flow reserve was calculated as the target-to-reference coronary reserve ratio. RESULTS: The median summed reversible score was 3 (range, 1-6). Intracoronary sonography showed occult atherosclerosis in 19 patients (95%), with RPA greater than 40% in 16 patients (80%). Mean RPA was significantly greater in the target vessels (46% +/- 14%) than in reference vessels (12% +/- 18%; P < 0.0001). Doppler flow velocity measurements showed abnormal vasodilation capacity (CFR < 2.5) in 14 patients (70%). Mean CFR was significantly lower in the target vessels than in the reference vessels (2.3 +/- 0.5 versus 3.1 +/- 0.6; P < 0.0001). A significant inverse correlation was seen between the summed reversible score and the coronary reserve ratio (y = 9.05x - 9.9; r = 0.70; P < 0.005). CONCLUSION: Reversible perfusion defects seen on SPECT images are often associated with angiographically unrecognized occult atherosclerotic changes and an abnormal vasodilation capacity of the coronary circulation. The tendency to dismiss abnormal exercise perfusion findings as false-positive in these patients may be unjustified.     

Assessment of left ventricular perfusion, volumes, and motion in mice using pinhole gated SPECT.

Quantitative functional normal data should be a prerequisite before applying SPECT in murine models of cardiac disease. Therefore, we investigated the capability of in vivo pinhole gated SPECT for establishment of a reference database for left ventricular myocardial perfusion, volumes, and motion in normal mice. METHODS: A small-animal dedicated pinhole gamma-camera with a field of view of 17 cm and a focal distance of 12 cm was used with a 1.5-mm pinhole and a 2.5-cm radius of rotation. Phantoms were designed to test spatial resolution and microvolume measurements of accuracy. Eight adult normal mice (CD1) were studied using a heated mixture of air (0.3 L/min) and 1.5%-2.5% isoflurane for anesthesia. For myocardial perfusion, 350-450 MBq of (99m)Tc-tetrofosmin were used in 0.15-0.25 mL. Gated acquisitions (8 or 10 time bins per cardiac cycle) were obtained using a 180 degrees circular arc and 48 anterior projections of 300 R-R intervals. Image reconstruction was done using a specific Algebraic Reconstruction Technique (ART) cone-beam algorithm. For quantification, reconstructed images were processed using standard nuclear medicine software. RESULTS: Millimetric spatial resolution and volume calibration linear relationships (r(2) = 0.99) in the 10- to 100-muL range were obtained in phantoms and used to scale in vivo volume values. In mice, left ventricular perfusion was lower in the apex (65% +/- 6%) versus lateral (72% +/- 5%), inferior (74% +/- 5%), septum (75% +/- 4%), and anterior (74% +/- 2%) walls. The left ventricular ejection fraction was 60% +/- 9%, end-diastolic volume was 50 +/- 8 muL, end-systolic volume was 20 +/- 6 muL, stroke volume was 29.5 +/- 6 muL, and cardiac output was 9.6 +/- 1.6 mL/min. Wall thickening was higher in the apex (47% +/- 12%) versus lateral (30% +/- 9%), inferior (33% +/- 8%), septum (37% +/- 10%), and anterior (33% +/- 10%) walls. CONCLUSION: This work shows that in vivo pinhole gated SPECT can be used for assessment of left ventricular perfusion, volumes, and cardiac function in normal mice.     

Attenuation correction in myocardial perfusion SPECT/CT: effects of misregistration and value of reregistration.

The accuracy of myocardial perfusion SPECT improves with attenuation correction. Algorithms for attenuation correction in hybrid SPECT/CT systems have the potential for misregistration of emission and transmission scans because CT and SPECT are obtained sequentially. Misregistration will influence regional tracer distribution and may reduce diagnostic accuracy. This study focused on the role of misregistration in cardiac SPECT/CT and the performance of a software-based approach for reregistration. METHODS: We included 105 consecutive patients who underwent clinical myocardial perfusion imaging on a SPECT/CT system. Images were quantitatively assessed for misregistration using fusion software. Results were recorded in millimeters in the x-, y-, and z-axes. Regional tracer uptake in 6 segments (anterior, septal, inferior, lateral, anteroapical, and inferoapical) for noncorrected and attenuation-corrected images before and after reregistration was obtained from polar maps. To determine the relative influence of misregistration, we correlated individual differences between noncorrected and attenuation-corrected images, as well as between attenuation-corrected images before and after reregistration, with the degree of misregistration in a multivariate analysis including additional clinical variables such as sex and body weight. RESULTS: The difference in regional radiotracer uptake was significant between noncorrected and attenuation-corrected images in all 6 segments and was most pronounced in the inferior wall. On multivariate analysis, misregistration contributed significantly to changes in radiotracer distribution in the anterior (P = 0.038), septal (P = 0.011), and inferior (P = 0.006) segments. The mean misregistration was 8.6 +/- 3.8 mm (1.25 +/- 0.55 pixel). Misregistration of one or more pixels was observed in 64% of studies. Reregistration of misalignment significantly affected regional radiotracer distribution in the segments shown to be influenced by misregistration. CONCLUSION: Misregistration occurs with SPECT/CT systems and influences regional tracer distribution on attenuation-corrected myocardial images. Reregistration of misaligned studies may be a useful tool for correction. The impact of this strategy on the diagnostic and prognostic accuracy of cardiac hybrid imaging needs to be determined.     

Functional evaluation of myocardial viability by99mTc tetrofosmin gated SPECT —A quantitative comparison with18F fluorodeoxyglucose positron emission CT (18F FDG PET)—

To validate functional analysis of gated SPECT in detecting myocardial viability, seventeen patients (male 15, female 2, mean age 58) with angiographically proven chronic ischemic heart disease (RCA 6, LAD 10, LCX 1) and eight normal volunteers (all male) were studied. All patients underwent 18F FDG PET and 99mTc tetrofosmin (TF) gated SPECT within a week. After being displayed in a polar map, myocardial perfusion was regionally determined by the mean count in 9 segments at end diastole (ED) and end systole (ES) in gated SPECT. Systolic function was determined by the count increase ratio from ED to ES (WTI: ES - ED/ED). Glucose metabolism was assessed by 18F FDG PET in the segments correspondent to those defined for SPECT. TF %uptake of < 60% was defined as hypoperfusion, and FDG %uptake of < 50% was defined as reduced glucose metabolism. RESULTS: The myocardial segments were classified into 3 categories: "normal" perfusion (n = 85), "mismatch" (reduced perfusion with reserved FDG uptake, n = 25) and "matched" reduced perfusion and metabolic reduction (n = 26). Mean WTI in "mismatch" segment was 0.38 +/- 0.21, and was significantly greater than that in "matched reduced" segments, 0.15 +/- 0.20 (p < 0.001). It was also greater than that in "normal" segments, 0.27 +/- 0.16. Regression analysis showed that association between WTI and FDG %uptake was significant (r = 0.57, p < 0.0005) for the ischemic segments ("mismatch" + "matched", n = 51), but the association was weak for the entire segments although it was statistically significant (r = 0.26, p = 0.02, n = 136). CONCLUSION: For the segments determined as infarct by perfusion image, systolic functional analysis by gated SPECT is helpful in differentiation of a viable myocardial region or artifact from a scar. Nevertheless, further clinical and technical assessment is required for ECG gating to eliminate overestimation of viability and to warrant clinical use.     

Risk stratification in patients with remote prior myocardial infarction using rest-stress myocardial perfusion spect: prognostic value and impact on referral to early catheterization

BACKGROUND: Little is known about the prognostic value of myocardial perfusion single photon emission computed tomography (SPECT) in patients with remote prior myocardial infarction (MI). METHODS AND RESULTS: We identified 1413 consecutive patients with remote prior MI who underwent rest-stress myocardial perfusion SPECT. Semiquantitative visual analysis of 20 SPECT segments was used to define the summed stress, rest, and difference scores. The number of non-reversible segments was used as an index of infarct size. During follow-up (>or=1 year), 118 hard events occurred: 64 cardiac deaths (CDs) and 54 recurrent MIs. Annual CD and hard event rates increased significantly as a function of SPECT abnormality. For summed stress scores less than 4, 4 to 8, 9 to 13, and more than 13, the annual CD rates were 0.4%, 0.9%, 1.7%, and 3.5%, respectively (P =.002). Patients with small MI (<4 non-reversible segments) and no or mild ischemia (summed difference score or=4 non-reversible segments) had moderate to high annual CD rates (3.7%-6.6%) regardless of the extent of ischemia. Nuclear testing added incremental prognostic information to pre-scan information. Compared with a strategy in which all patients are referred to catheterization, a strategy that referred only those patients with a risk for CD of greater than 1% by myocardial perfusion SPECT resulted in a 41.6% cost savings. CONCLUSIONS: Myocardial perfusion SPECT adds incremental value to pre-scan information and is highly predictive and cost-efficient in the risk stratification of patients with remote prior MI. Patients with normal or mildly abnormal scan results or small MI in combination with absent or mild ischemia have a low risk for CD.     

Prognostic value of myocardial perfusion tomographic imaging in patients after percutaneous transluminal coronary angioplasty

PURPOSE: The authors assessed the prognostic value of stress myocardial perfusion tomographic imaging (SPECT) in patients with recurrent angina or inconclusive results of exercise electrocardiographic tests after successful percutaneous transluminal coronary angioplasty (PTCA). MATERIALS AND METHODS: After PTCA, 70 patients (54 men, 16 women; 41 after myocardial infarction; mean age, 56 +/- 9 years) underwent TI-201 or Tc-99m sestamibi SPECT studies. SPECT patterns were divided into normal (n = 25), fixed defects (n = 15), and reversible or combined fixed plus reversible defects (n = 30). A cardiac event was defined as either cardiac death, nonfatal myocardial infarction, or unstable angina requiring further revascularization. RESULTS: During an average follow-up of 25 +/- 10 months, two patients had severe outcomes (one cardiac death and one nonfatal myocardial infarction), and revascularization was required in 13 patients. In patients with normal SPECT or fixed defects, the annual event rate was low (1.2%), with only one revascularization. In patients with reversible or combined defects, the annual event rate was significantly greater (22.4%; chi square = 17.32, P = 0.00003). CONCLUSIONS: Normal perfusion or fixed defects predict a benign prognosis in patients after successful PTCA. The presence of stress-induced reversible defects appears to be the best predictor of future cardiac events.