Gated 99mTc-tetrofosmin and 18F-FDG studies: a comparison of single-acquisition and separate-acquisition protocols

18F-FDG is a well-established tracer for evaluating myocardial viability, as is (99m)Tc-tetrofosmin (TET) for evaluating myocardial perfusion. Dual-isotope single-acquisition (DISA) studies using a (99m)Tc perfusion agent and (18)F-FDG have been performed to evaluate myocardial viability. The purpose of this investigation was to determine whether there is a difference in the results of gated SPECT DISA, compared with gated SPECT DIDA (dual-isotope dual-acquisition) studies using (99m)Tc-TET/(18)F-FDG and a high-energy collimated dual-head SPECT system. METHODS: We prospectively studied 13 patients with depressed left ventricular function using both acquisition protocols. Summed rest scores were calculated for both (99m)Tc and (18)F-FDG studies using a 12-segment model and a 5-grade severity score. Images were evaluated by a single reader who did not know whether the images were acquired separately or simultaneously. RESULTS: The concordance of DISA and DIDA protocols for (99m)Tc-TET when allowing no difference in the SRS was 57%, or 89 of 156 segments. The concordance of DISA and DIDA protocols for (18)F-FDG was 86%, or 134 of 156 segments. The concordance of segments determined to be viable versus nonviable was 92%, or 143 of 156 segments. Ejection fraction measurements obtained by gated (99m)Tc-TET studies correlated strongly with those obtained by gated (18)F-FDG studies. CONCLUSION: A high concordance for (18)F-FDG studies was shown between gated DISA and gated DIDA. A lower concordance was shown between gated DISA and gated DIDA studies using (99m)Tc-TET, most likely because of downscatter from (18)F into the (99m)Tc window. An excellent concordance was demonstrated between the 2 techniques for viability assessment. The gated (99m)Tc-TET/(18)F-FDG DISA protocol can be both a reliable and an efficient way to evaluate myocardial function, perfusion, and viability.     

Comparison of microsphere-equivalent blood flow (15O-water PET) and relative perfusion (99mTc-tetrofosmin SPECT) in myocardium showing metabolism-perfusion mismatch.

Myocardial perfusion imaging with (99m)Tc-tetrofosmin is based on the assumption of a linear correlation between myocardial blood flow (MBF) and tracer uptake. However, it is known that (99m)Tc-tetrofosmin uptake is directly related to energy-dependent transport processes, such as Na(+)/H(+) ion channel activity, as well as cellular and mitochondrial membrane potentials. Therefore, cellular alterations that affect these energy-dependent transport processes ought to influence (99m)Tc-tetrofosmin uptake independently of blood flow. Because metabolism ((18)F-FDG)-perfusion ((99m)Tc-tetrofosmin) mismatch myocardium (MPMM) reflects impaired but viable myocardium showing cellular alterations, MPMM was chosen to quantify the blood flow-independent effect of cellular alterations on (99m)Tc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF (MBF_micr; (15)O-water PET) and (99m)Tc-tetrofosmin uptake in MPMM and in "normal" myocardium. METHODS: Forty-two patients with severe coronary artery disease, referred for myocardial viability diagnostics, were examined using (18)F-FDG PET and (99m)Tc-tetrofosmin perfusion SPECT. Relative (18)F-FDG and (99m)Tc-tetrofosmin uptake values were calculated using 18 segments per patient. Normal myocardium and MPMM myocardium were classified using a previously validated (99m)Tc-tetrofosmin SPECT/(18)F-FDG PET score. In addition, (15)O-water PET was performed to assess kinetic-modeled MBF (MBF_kin), the water-perfusable tissue fraction (PTF), and the resulting MBF_micr (MBF_kin x PTF), which is comparable to tracer uptake values. (99m)Tc-tetrofosmin uptake and MBF_micr values were calculated for all normal and MPMM segments and averaged within their respective classifications. RESULTS: Mean relative (99m)Tc-tetrofosmin uptake was 86% +/- 1% in normal myocardium and 56% +/- 1% in MPMM, showing a significant difference (P < 0.001), as was expected from the classification. Contrary to these findings, mean MBF_micr in MPMM myocardium was 0.60 +/- 0.03 mL x min(-1) x mL(-1), which did not significantly differ from normal myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)). All values are given as mean +/- SEM. CONCLUSION: Differences between reduced (99m)Tc-tetrofosmin uptake and the unchanged MBF_micr in MPMM myocardium suggest that the pathophysiologic basis of MPMM is not a blood flow reduction but cellular alterations that affect uptake and retention of (99m)Tc-tetrofosmin independently of blood flow. Therefore, it seems that perfusion deficits in MPMM myocardium are greatly overestimated by (99m)Tc-tetrofosmin and that it tends to give false-positive findings.     

Baseline/postnitrate tetrofosmin SPECT for myocardial viability assessment in patients with postischemic severe left ventricular dysfunction: new evidence from MRI.

The aim of this study was to compare (99m)Tc-tetrofosmin SPECT with contrast-enhanced MRI (ceMRI), a new direct sign of myocardial fibrosis. METHODS: We studied 21 patients (age, 60 +/- 11 y; 19 male) with previous myocardial infarction and severe left ventricular dysfunction (ceMRI EF, 29% +/- 6%). All patients underwent resting and postnitrate (intravenous isosorbide dinitrate) (99m)Tc-tetrofosmin gated SPECT as well as ceMRI. Scintigraphic analysis was performed using quantitative perfusion SPECT (QPS), providing the percentage radiotracer uptake and defect severity in a 20-segment model. Hyperenhancement was defined by the increase of ceMRI signal intensity 20 min after intravenous injection of gadolinium-diethylenetriaminepentaacetic acid and its regional extension as the percentage of the total segment area. RESULTS: In ceMRI dysfunctional segments, the correlation between the extent of hyperenhancement and both (99m)Tc-tetrofosmin uptake and defect severity was significantly better after nitrate administration rather than at rest (P < 0.0001). Using a ceMRI cutoff below 40%, 102 of 196 (52%) segments were viable, whereas 94 (48%) segments were not viable. According to receiver-operating characteristic curve analysis, diagnostic accuracies were higher for postnitrate (99m)Tc-tetrofosmin uptake as well as perfusion defect severity than using resting data (0.84 vs. 0.71, P < 0.001; 0.89 vs. 0.76, P < 0.001, respectively). CONCLUSION: After nitrate administration, (99m)Tc-tetrofosmin uptake and perfusion defect severity were closely related to ceMRI, demonstrating, in vivo, the existence of an inverse correlation between the transmural distribution of fibrosis and tracer delivery to the myocardium.     

Evaluation of left ventricular wall motion, volumes, and ejection fraction by gated myocardial tomography with technetium 99m-labeled tetrofosmin: A comparison with cine magnetic resonance imaging

Background  Whether left ventricular function can be assessed accurately by gated single photon emission computed tomography (SPECT) in patients with myocardial infarction and severe perfusion defects is not well known. Methods and Results  Twenty-five patients with an acute myocardial infarction underwent ^99mTc-labeled tetrofosmin (^99mTc-tetrofosmin) gated SPECT and cine magnetic resonance imaging (MRI). Wall motion was assessed in 13 left ventricular segments using a 5-point scoring system ranging from 3 (normal) to-1 (dyskinetic). Exact agreement for wall motion scores between gated SPECT and MRI was excellent (92%, kappa=0.82). Furthermore, correlations between the two techniques were also good for end-diastolic volume (r=0.81, P<.0001), end-systolic volume (r=0.92, P<.0001), and ejection fraction (r=0.93, P<.0001). Conclusion  In patients with a recent myocardial infarction, ^99mTc-tetrofosmin gated SPECT provides reliable evaluation of global and regional ventricular function and volumes.     

Electrocardiographic-gated dual-isotope simultaneous acquisition SPECT using 18F-FDG and 99mTc-sestamibi to assess myocardial viability and function in a single study

Purpose Dual-isotope simultaneous acquisition single-photon emission computed tomography (DISA SPECT) with ¹⁸F-fluorodeoxyglucose (FDG) and ^99mTc-sestamibi appears attractive for the detection of viable myocardium because it permits simultaneous assessment of glucose utilisation and perfusion. Another potential benefit of this approach is that the measurement of left ventricular (LV) function may be possible by ECG gating. The aim of this study was to test the hypothesis that both myocardial viability and LV function can be assessed by a single ECG-gated ¹⁸F-FDG/^99mTc-sestamibi DISA SPECT study, based on comparison with ¹⁸F-FDG/¹³N-ammonia positron emission tomography (PET) and magnetic resonance imaging (MRI) as reference techniques.Methods Thirty-three patients with prior myocardial infarction underwent ECG-gated ¹⁸F-FDG/^99mTc-sestamibi DISA SPECT and ¹⁸F-FDG/¹³N-ammonia PET on a single day. Of these, 25 patients also underwent cine-MRI to assess LV function. The LV myocardium was divided into nine regions, and each region was classified as viable or scar using a semiquantitative visual scoring system as well as quantitative analysis. The global and regional LV function measured by gated SPECT was compared with the results of MRI.Results There was good agreement in respect of viability (90–96%, 0.74–0.85) between DISA SPECT and PET by either visual or quantitative analysis. Furthermore, although both global and regional LV function measured by gated SPECT agreed with those by MRI, ^99mTc-sestamibi showed a closer correlation with MRI than did ¹⁸F-FDG.Conclusion In conclusion, ECG-gated DISA SPECT provides information on myocardial viability, as well as global and regional LV function, similar to that obtained by PET and MRI.     

Comparison of technetium 99m-tetrofosmin and thallium-201 single photon emission computed tomographic imaging for the assessment of viable myocardium in patients with left ventricular dysfunction

Background  Tetrofosmin is a new technetium 99m-labeled myocardial perfusion agent that has demonstrated favorable imaging characteristics in recent clinical trials. However, it is not certain whether ^99mTc-tetrofosmin compared with thallium 201 would underestimate myocardial viability in regions with left ventricular dysfunction. Methods  To this end 15 patients (mean age 52±7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 35%±8%) documented on angiography underwent both quantitative rest-redistribution ²⁰¹TI and rest ^99mTc-tetrofosmin single photon emission computed tomography imaging. Results  Of 240 total segments on rest-redistribution ²⁰¹TI protocol 139 (58%) segments had irreversible ²⁰¹TI defects. Of these segments 79 (57%) had only mild to moderate reduction of ²⁰¹TI uptake (51% to 85% of normal uptake), whereas the remaining 60 (43%) had severely reduced tracer uptake (≤50% of normal uptake). On ^99mTc-tetrofosmin protocol 180 (75%) segments had abnormal ^99mTc-tetrofosmin uptake; of these segments 120 (67%) had mild to moderate reduction of ^99mTc-tetrofosmin uptake, whereas 60 (33%) had severely reduced activity. Among hypokinetic regions concordance between ²⁰¹TI and ^99mTc-tetrofosmin regarding myocardial viability with a cutoff point of 50% of peak activity was obtained in 28 (90%) of 31 segments (K′=0.80), leaving only 3 of 31 regions discordant (p=NS). Similarly, among akinetic or dyskinetic regions concordance between the two tracers regarding myocardial viability was achieved in 54 (93%) regions (K′=0.75), leaving only 4 of the 58 regions discordant (p=NS). Conclusions  These data show that when the severity of uptake was considered within abnormal segments, a similar amount of ²⁰¹TI viable regions were observed by ^99mTc-tetrofosmin. Thus these two agents may provide comparable information about myocardial viability when quantitative analysis of defect severity is performed.     

Effect of intramyocardial injection of autologous bone marrow-derived mononuclear cells on perfusion, function, and viability in patients with drug-refractory chronic ischemia.

Intramyocardial injection of bone marrow cells has been proposed as a new therapeutic option for patients with chronic ischemic heart disease. We investigated whether autologous bone marrow-derived mononuclear cell injection into the myocardium of patients with drug-refractory ischemia reduces anginal symptoms, improves left ventricular (LV) function, increases myocardial perfusion, and alters the extent of scar tissue. METHODS: In 25 patients (mean age +/- SD, 64 +/- 10 y; 21 male) with drug-refractory angina pectoris (Canadian Cardiovascular Society [CCS] class III-IV), despite optimized medical therapy and without options for conventional revascularization, bone marrow was aspirated from the iliac crest. Mononuclear cell injections were targeted at myocardial regions with stress-induced ischemia on gated (99m)Tc-tetrofosmin SPECT. Anginal symptoms were reassessed at 3- and 6-mo follow-up. At baseline and 3-mo follow-up, gated (99m)Tc-tetrofosmin SPECT and (18)F-FDG SPECT were performed to assess LV function, LV volumes, myocardial perfusion (stress and rest, 17-segment model), and extent of scar tissue. RESULTS: Mean CCS score improved from 3.4 +/- 0.6 at baseline to 2.3 +/- 0.6 at 3 mo (P < 0.01) and remained unchanged at 6 mo (2.3 +/- 0.6; P < 0.01 vs. baseline and P = not significant [NS] vs. 3 mo). Gated (99m)Tc-tetrofosmin SPECT demonstrated an increased LV ejection fraction (from 47.6% +/- 13.5% to 54.1% +/- 16.9%; P < 0.01) and a reduced LV end-systolic volume (from 81 +/- 68 mL to 75 +/- 70 mL; P < 0.01). Segmental regional wall thickening increased from 34% +/- 12% at baseline to 39% +/- 17% at 3-mo follow-up (P = 0.01). The number of segments with stress-inducible ischemia per patient decreased from 4.6 +/- 3.2 to 2.0 +/- 2.6 (P < 0.01). Both segmental stress and segmental rest score improved, although the improvement in stress score was more pronounced (decrease in segmental stress score 0.22 +/- 0.20 vs. decrease in segmental rest score 0.04 +/- 0.06; P < 0.01). Myocardial perfusion improved in 53% of the injected segments and in 13% of the noninjected segments (P < 0.01). The percentage of myocardial segments with some extent of scar remained unchanged at 3-mo follow-up (13% vs. 12%; P = NS). CONCLUSION: Autologous bone marrow-derived mononuclear cell injection in patients with drug-refractory angina and chronic ischemia improves anginal symptoms, increases LV function, and predominantly enhances myocardial stress perfusion in injected segments, whereas the extent of myocardial scar tissue remains unchanged.     

Feasibility and image quality of dual-isotope SPECT using 18F-FDG and (99m)Tc-tetrofosmin after acipimox administration.

Currently, with the rapidly increasing number of patients with heart failure due to chronic coronary artery disease, the need for viability studies to guide treatment in these patients is increasing. The most accurate method for viability assessment is metabolic imaging with (18)F-FDG with PET or SPECT. To obtain excellent image quality in all patients, the (18)F-FDG studies should be performed during hyperinsulinemic euglycemic clamping. However, this approach is time-consuming and is not feasible in busy nuclear medicine laboratories. Recently, the use of a nicotinic acid derivative, acipimox, has been suggested, but limited data are available on the image quality of the (18)F-FDG studies using this approach. METHODS: We evaluated the feasibility and image quality of (18)F-FDG SPECT (with dual-isotope simultaneous acquisition (DISA) using (99m)Tc-tetrofosmin to assess perfusion) after acipimox administration in 50 nondiabetic patients. The image quality of both (18)F-FDG and (99m)Tc-tetrofosmin was assessed visually and quantitatively using myocardium-to-blood-pool (M/B) ratios as a measure of target-to-background ratio. The image quality and diagnostic value of DISA (99m)Tc-tetrofosmin SPECT was compared with standard (99m)Tc-tetrofosmin SPECT at baseline. RESULTS: After acipimox administration, the plasma levels of free fatty acids were extremely low (68 +/- 89 nmol/L). No severe side effects were observed, only paroxysmal flushing. The (18)F-FDG image quality was good in 46 patients (92%) and moderate but still interpretable in the other 4 patients (8%). The clinical information of the baseline (99m)Tc-tetrofosmin SPECT was retained in the DISA (99m)Tc-tetrofosmin SPECT images because we did observe no substantial fill-in of perfusion defects by high (18)F-FDG uptake in the same segment. CONCLUSION: Cardiac (18)F-FDG SPECT after acipimox is safe and resulted consistently in good image quality; this simple approach may be the method of choice for routine cardiac metabolic imaging.     

Influence of SPECT attenuation correction on the quantification of hibernating myocardium as derived from combined myocardial perfusion SPECT and 18F-FDG PET

Background

To evaluate the influence of SPECT attenuation correction on the quantification of hibernating myocardium derived from perfusion SPECT and ¹⁸F-FDG PET.

Methods and Results

20 patients underwent rest ^99mTc-tetrofosmin perfusion SPECT/CT and ¹⁸F-FDG PET/CT. Perfusion images were reconstructed without attenuation correction (NC), with attenuation correction based on the CT from the SPECT/CT (AC_SPECT), and with attenuation correction based on the CT from the PET/CT (AC_PET). Another 56 patients had rest ^99mTc-tetrofosmin perfusion SPECT and ¹⁸F-FDG PET/CT. Perfusion images were reconstructed as NC and AC_PET. The amounts of hibernating myocardium and scar were quantified with QPS^® and corresponding AC and NC normative databases. In both cohorts, perfusion in the inferior wall was higher in the AC scans than without AC. Global and regional values for total perfusion deficit (TPD), hibernation and scar areas did not differ between NC, AC_SPECT, and AC_PET scans. In a retrospective evaluation with 7% cut-off of hibernating myocardium as a condition for revascularization, the therapeutic approach would have been altered in 5 of 56 patients, if the AC_PET approach had been used.

Conclusions

AC of SPECT perfusion scans with an attenuation map derived from PET/CT scans is feasible. If AC is unavailable, perfusion scans should be compared to NC normative databases for assessing TPD, hibernation, and mismatch. It should be taken into account that in approximately 10% of the patients, a therapeutic recommendation based on published thresholds for hibernating myocardium would be altered if NC scans were used as compared to AC scans.     

Evaluation of myocardial viability following acute myocardial infarctic using201Tl SPECT after thallium-glucose-insulin infusion —Comparison with18F-FDG positron emission tomography—

OBJECTIVE AND METHODS: The aim of this study was to evaluate myocardial viability in patients after acute myocardial infarction (AMI). We compared 201Tl SPECT after 201Tl with GIK (10% glucose 250 ml, insulin 5 U and KCl 10 mEq) infusion (GIK-201Tl) with resting 201Tl and 99mTc-pyrophosphate (PYP) dual SPECT, positron emission computed tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) in 21 patients with their first AMI, who all underwent successful reperfusion. GIK-201Tl SPECT, 201Tl and 99mTc-PYP dual SPECT were done within 10 days after admission and 18F-FDG-PET was performed at 3 weeks. GIK-201Tl SPECT was obtained after 30 min of GIK-201Tl infusion. 18F-FDG (370 MBq) was injected intravenously after oral glucose (1 g/ kg) loading, and then PET was obtained. PET and SPECT images were divided into 20 segments. Regional tracer uptake was scored using a 4-point scoring system (3 = normal to 0 = defect), and summed to a regional uptake score (RUS). Regional area means the infarcted area in which 99mTc-PYP accumulated. The number of decreased uptake segments (ES) was then determined. The infarcted area was defined as the area of 99mTc-PYP uptake. RESULTS: The ESs for the GIK-201Tl and 18F-FDG-PET images were significantly lower than the number of 99mTc-PYP uptake segments. The RUS for GIK-201Tl was higher than that for resting-201Tl imaging and similar to those for 18F-FDG-PET. CONCLUSIONS: In the detection of myocardial viability following AMI, GIK-201Tl imaging is useful with findings similar to those of 18F-FDG-PET.     

Evaluation of regional myocardial perfusion in patients with severe left ventricular dysfunction: Comparison of 13N-ammonia PET and 99mTc sestamibi SPECT

Objective

Positron emission tomography (PET) scanning with ¹³N-ammonia and ¹⁸FDG is well established for the detection of myocardial viability. Due to the limited availability of PET facilities, recent studies have combined technetium 99m sestamibi single photon emission computed tomography (SPECT) with ¹⁸FDG PET or ¹⁸FDG SPECT. This approach enables simultaneous assessment of regional myocardial blood flow and metabolism and substantially increases the capacity for viability detection. To validate whether ^99mTc-Sestamibi SPECT can replace ¹³N-ammonia PET, we compared these two modalities in patients with severe left ventricular dysfunction due to coronary artery disease.

Materials and Methods

Thirty-one patients (mean age 57±8 years; mean ejection fraction 27%±8%) with angiographically verified coronary artery disease were included. In random order, ammonia-PET and sestamibi-SPECT scans were performed. In a 20-segment model of the left ventricle, two blinded observers scored a total of 610 segments on a five-point scale. In a subset of 20 patients, 400 segments were scored twice to evaluate the observer variations of the two techniques. Segmental score differences were used to compare the imaging modalities. The impact on viability detection was assessed by combining the two flow tracers with FDG PET.

Results

Segmental comparison of the PET and SPECT studies yielded similar (difference ≤1) results in 74% of segments, reflecting regional concordance values in the lateral, apical, anterior, septal, and inferior myocardial walls of 86%, 82%, 71%, 66%, and 63%, respectively. The differences in the septal and inferior walls were primarily due to overestimation of perfusion defects by sestamibi SPECT, which yielded a higher proportion of mismatch patterns in those regions. The overall observer variations of the PET and SPECT studies were 7.5% and 5.8%.

Conclusion

Myocardial perfusion imaging with ¹³N-ammonia PET and ^99mTc-sestamibi SPECT yielded similar results in patients with severe left ventricular dysfunction, except for the septal and inferior regions. In these regions, SPECT tended to overestimate perfusion defects. Hence, attenuation correction should be considered when combining FDG PET and sestamibi SPECT for diagnosing myocardial viability to avoid overestimation of mismatch patterns in those regions.     

Nitrate administration to enhance the detection of myocardial viability by technetium-99m tetrofosmin single-photon emission tomography

A comparison was performed between technetium-99m tetrofosmin myocardial perfusion tomography at baseline and after nitrate administration, using a 2-day protocol, and rest-reinjection thallium-201 single-photon emission tomography (SPET) studies in order to assess whether nitrates enhance the detection of viable myocardium with^99mTc-tetrofosmin. Fifteen patients with coronary artery disease, previous myocardial infarction and a left ventricular ejection fraction <40% underwent²⁰¹T1 rest-injection and^99mTc-tetrofosmin. baseline-postnitroglycerin (0.4 mg sublingually) SPET studies, within 48 h. Tomograms based on the three spatial planes were divided into 15 segments and regional tracer uptake was quantitatively analysed. Viability was defined as presence of tracer uptake >50% of peak activity on baseline studies or after reversibility. The percentage of peak activity of^99mTc-tetrofosmin at baseline correlated with that of 201T1 (r=0.82,P <0.001). On baseline^99mTc-tetrofosmin studies, 73 of the 225 segments that were analysed had <50% of peal. activity. Fifteen percent of these segments showed reversibility after nitrate administration, with an increase in^99mTc-tetrofosmin uptake from 40%±9% to 57%±9% of peak activity (P=0.003). All reversible segments after nitrate administration had viability criteria on²⁰¹Tl studies, but 20 segments that were non-viable on^99mTc-tetrofosmin. studies were viable on²⁰¹Tl studies. Using a threshold value of >40% of peak activity, only seven segments remained non-viable on^99mTc-tetrofosmin studies. Overall agreement between^99mTc-tetrofosmin with nitrates and²⁰¹Tl-reinjection regarding the presence of myocardial viability was 90%. Detection of myocardial viability with^99mTc-tetrofosmin. was enhanced after nitrate administration, correlating with viability criteria observed on thallium studies.     

Comparative assessment of18F-fluorodeoxyglucose PET and99mTc-tetrofosmin SPECT for the prediction of functional recovery in patients with reperfused acute myocardial infarction

Purpose: Although preserved glucose metabolism is considered to be a marker of myocardial viability in the chronic stage, it has not been fully elucidated whether this is also true with regard to reperfused acute myocardial infarction (AMI). The aim of this study was to compare the diagnostic performance of^99mTc-tetrofosmin SPECT and¹⁸F-fluorodeoxyglucose (FDG) PET for the prediction of functional recovery in reperfused AMI.Methods: The study population comprised 28 patients. Both tetrofosmin SPECT and FDG PET were performed in all 28 patients at ca. 2 weeks and in 23 at 6 months. The tetrofosmin and FDG findings in infarct-related segments were compared with the regional wall motion score assessed by left ventriculography over 6 months to determine the predictive value for functional recovery.Results: Of 120 infarct-related segments, 83 had preserved flow (tetrofosmin uptake ≥50%) and 81 had preserved glucose metabolism (FDG uptake ≥40%). The sensitivity and specificity of tetrofosmin SPECT for the prediction of functional recovery tended to be superior to those of FDG PET (90.0% and 72.5% vs 85.0% and 67.5%, respectively). Thirteen segments with preserved flow and decreased glucose metabolism demonstrated marked recovery of contractile function from 2.5±1.0 to 1.4±1.4 (p<0.01), with restoration of glucose metabolism at 6 months. In contrast, 11 segments with decreased flow and preserved glucose metabolism demonstrated incomplete functional improvement from 3.0±0.8 to 2.2±1.2.Conclusion: In the subacute phase, preserved myocardial blood flow is more reliable than glucose metabolism in predicting functional recovery in reperfused myocardium.     

Incremental prognostic value of dobutamine–atropine stress 99mTc-tetrofosmin myocardial perfusion imaging for predicting outcome in diabetic patients with limited exercise capacity

Purpose This study assessed the incremental value of dobutamine stress ^99mTc-tetrofosmin single-photon emission computed tomography (SPECT) for the prediction of cardiac events in diabetic patients with limited exercise capacity.Methods The study population comprised 125 consecutive diabetic patients (mean age 61±9 years, 61% men) who were unable to perform an exercise test and underwent dobutamine ^99mTc-tetrofosmin SPECT. Follow-up was successful in 124 (99%) patients. Three patients who underwent early revascularisation (within 60 days) were excluded. End-points during follow-up were cardiac death and non-fatal myocardial infarction.Results An abnormal scan (with the presence of reversible or fixed perfusion defects) was observed in 76 (63%) patients. During the follow-up (3.4±1.5 years), 36 patients died (19 cardiac deaths) and four patients had non-fatal myocardial infarction. Cardiac death occurred in one of 49 (2%) patients with a normal myocardial perfusion study and in 18 of 75 (24%) patients with an abnormal study (p<0.001). Abnormal scan was incremental to the clinical parameters in predicting cardiac death (²=48 vs 39, p<0.05) and hard cardiac events (²=50 vs 43, p<0.05).Conclusion Dobutamine stress ^99mTc-tetrofosmin SPECT provides prognostic information additional to clinical data for the prediction of cardiac death and hard cardiac events in diabetic patients unable to perform an exercise test.     

Regional alterations in myocardial sympathetic innervation in patients with transient left-ventricular apical ballooning (Tako-Tsubo cardiomyopathy)

Background  Excess sympathetic nervous activity was proposed to play a crucial role in the pathogenesis of transient left-ventricular apical ballooning (TLVAB, also known as Tako-Tsubo cardiomyopathy). This study was conducted to assess presynaptic adrenergic alterations in the dysfunctional myocardium of patients with TLVAB. Methods and Results  Ten consecutive patients undergoing coronary angiography for acute coronary syndrome who fulfilled the proposed Mayo Clinic criteria for the diagnosis of TLVAB were investigated. Myocardial iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) studies (planar and single-photon emission computed tomography [SPECT]) were performed to evaluate adrenergic innervation. Concomitantly, myocardial perfusion was assessed by means of technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) SPECT. In all patients, angiography revealed typical ballooning of the left-ventricular (LV) apex and hyperkinesis of the basal LV segments (overall ejection fraction, 41%±5% [mean±SEM]). Planar ¹²³I-MIBG scans revealed decreased heart-to-mediastinum ratios at early (20 minutes) and delayed (4 hours) images (2.1±0.1 and 1.9±0.1, respectively). The cardiac washout rate of ¹²³I-MIBG on the late images was increased to 34%±3%. The ¹²³I-MIBG uptake on SPECT scans was obviously reduced in the akinetic LV apex (defect score, 3.30±0.34), whereas ^99mTc-MIBI SPECT indicated normal or only mildly reduced perfusion within this region (defect score, 0.89±0.35). Conclusions  Our study indicates a functional alteration in presynaptic sympathetic neurotransmission in patients with TLVAB, and suggests a pathophysiologic explanation of the impairment of LV function.     

Enhanced detection of reversible myocardial hypoperfusion by technetium 99m-tetrofosmin imaging and first-pass radionuclide angiography after nitroglycerin administration

Background  Reversal of ischemia after myocardial infarction by revascularization is worth-while only if viability exists in a sufficiently large portion of the left ventricle. Methods and Results  To determine myocardial hypoperfusion reversibility and its influence on segmental and global function, we studied 50 patients after myocardial infarction. Three technetium 99m-tetrofosmin scintigraphies were performed: 1 at rest, 1 after 0.6 mg sublingual nitroglycerin (NTG), and 1 after injection at peak stress. First-pass multigated radionuclide angiography was obtained at rest and after NTG. Each patient also underwent a stress redistribution-reinjection thallium-201 scintigraphy. During stress ^99mTc-tetrofosmin, 104 segments had normal uptake, 51 showed moderately reduced uptake, and 186 had severely reduced uptake. Of these 186 segments, 33 (18%) improved at rest, and 41 (22%) improved only after NTG. Fifty-nine (79%) of these segments with improved uptake were also found to have reversible defects on ²⁰¹Tl imaging. In the 26 patients with ventricular dysfunction, a 73% agreement was found between the functional and ^99mTc-tetrofosmin uptake post-NTG improvement, whereas a 69% agreement was found with thallium reinjection. No significant differences were seen between ^99mTc-tetrofosmin and ²⁰¹Tl imaging. Conclusion  Nitroglycerin administration during ^99mTc-tetrofosmin scintigraphy improves the detection of myocardium with reversible hypoperfusion in patients with a previous myocardial infarction.     

Myocardial imaging with 18F-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis

Purpose Despite accumulating reports on the clinical value of ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (¹⁸F-FDG PET) and magnetic resonance imaging (MRI) in the assessment of cardiac sarcoidosis, no studies have systematically compared the images of these modalities. Methods Twenty-one consecutive patients with suspected cardiac sarcoidosis underwent cardiac examinations that included ¹⁸F-FDG PET and MRI. The association of ¹⁸F-FDG PET and MRI findings with blood sampling data such as serum angiotensin converting enzyme levels was also evaluated. Results Eight of 21 patients were diagnosed as having cardiac sarcoidosis according to the Japanese Ministry of Health and Welfare Guidelines for Diagnosing Cardiac Sarcoidosis. Sensitivity and specificity for diagnosing cardiac sarcoidosis were 87.5 and 38.5%, respectively, for ¹⁸F-FDG PET, and 75 and 76.9%, respectively, for MRI. When the ¹⁸F-FDG PET and MRI images were compared, 16 of 21 patients showed positive findings in one (n = 8) or both (n = 8) of the two modalities. In eight patients with positive findings on both images, the distribution of the findings differed among all eight cases. The presence of positive findings on ¹⁸F-FDG PET was associated with elevated serum angiotensin-converting enzyme levels; this association was not demonstrated on MRI. Conclusions Both ¹⁸F-FDG PET and MRI provided high sensitivity for diagnosing cardiac sarcoidosis in patients with suspected cardiac involvement, but the specificity of ¹⁸F-FDG PET was not as high as previously reported. The different distributions of the findings in the two modalities suggest the potential of ¹⁸F-FDG PET and MRI in detecting different pathological processes in the heart.     

Influence of 99mTc-tetrofosmin SPECT myocardial perfusion imaging on the prediction of future adverse cardiac events

Background  The impact of myocardial perfusion imaging (MPI) on prediction of risk for future cardiac events was examined by comparing predictions based on clinical information alone and in combination with MPI findings. Methods and Results  A 3-cardiologist Cardiac Event Prediction Panel (CEPP) estimated three-year cardiac event (non-fatal MI; aborted sudden cardiac death; cardiac death) risk based on clinical data (C) for 371 subjects. CEPP repeated this estimation after receiving Summed Stress Scores (SSS) and Summed Rest Scores (SRS) from blinded reading of rest-stress ^99mTc-tetrofosmin MPI SPECT studies (C + MPI). The C and C + MPI estimates were then compared with three-year and total event rates. MPI was normal (SSS ≤ 3) in 227 patients (61%), mildly abnormal (SSS 4-8) in 31 (8%), moderately abnormal (SSS 9-13) in 36 (10%), and severely abnormal (SSS > 13) in 77 (21%). Eighteen cardiac events occurred within 3 years and 33 occurred during a mean follow-up of 3.9 years. C + MPI estimates of low risk (<1-1.5%/year) identified significantly more patients who did not have events than C. C + MPI three-year event-rate predictions were more accurate than those made with C (P < .01). C + MPI categorization also provided better delineation of incremental risk on time-to-event analyses. Conclusions   ^99mTc-tetrofosmin MPI single photon emission computed tomography (SPECT) findings significantly improve accuracy of cardiac event rate prediction compared to those based on clinical information alone. This study was performed by GE Healthcare.     

Comparison of <Superscript>99m</Superscript>Tc-annexin A5 with <Superscript>18</Superscript>F-FDG for the detection of atherosclerosis in ApoE−/− mice

Purpose ^99mTc-annexin A5, a marker of ongoing apoptosis, and ¹⁸F-FDG, a marker of the increased metabolism of inflammatory cells, are supposed to be useful in the detection of metabolically active atheroma. This study reports a comparison of the intralesional distribution of these tracers in relation to lesion development in ApoE−/− mice. Methods Male ApoE−/− mice (n = 12–14/group) were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks, ^99mTc-annexin A5 or ¹⁸F-FDG was injected and the aortas were harvested for autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a semiquantitative parameter for evaluating lesion development). Results Both ^99mTc-annexin A5 and ¹⁸F-FDG showed preferential uptake into atherosclerotic lesions, with higher uptake levels for ¹⁸F-FDG (mean, 56.07 %ID×kg/m²) than for ^99mTc-annexin A5 (mean, 10.38 %ID×kg/m²). The regional uptake levels of each tracer correlated with the Oil Red O staining score (r = 0.65, p < 0.05 for ^99mTc-annexin A5; r = 0.56, p < 0.05 for ¹⁸F-FDG). The uptake ratios of advanced lesions (score >0.5) to early lesions (score <0.5) were significantly higher for ^99mTc-annexin A5 than for ¹⁸F-FDG (f = 4.73, p = 0.03). Conclusion Both ^99mTc-annexin A5 and ¹⁸F-FDG accumulate in atherosclerotic lesions and correlate with the severity of each lesion. The higher absolute uptake levels of ¹⁸F-FDG may be advantageous for lesion detection, whereas the preferential uptake of ^99mTc-annexin A5 in advanced lesions may be a useful indicator of late-stage lesions or vulnerable plaque transformation.