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Purpose: Guidelines propose different rest-stress activity ratios (RSAR) for one-day stress-first SPECT myocardial perfusion imaging (MPI), but evidence is limited. Our aim was to determine and validate the minimal RSAR resulting in the same diagnostic outcome in one-day stress-first SPECT MPI., Methods: Forty-seven patients referred for rest after stress CZT-SPECT/CT MPI were prospectively included. Rest acquisitions were performed 3 h after stress. In addition to the stress and rest acquisitions, the first 22 patients underwent an additional acquisition prior to the rest injection to determine the remaining stress activity. Next, we simulated six RSARs varying from 1.0 to 3.5 in both patients and a phantom and compared the images to those using the reference RSAR of 4.0. Differences in summed difference score (SDS) >2 or ischemic defect interpretation were considered to significantly influence diagnostic outcome. After deriving the minimal RSAR, it was validated in 25 additional patients by comparing it to a RSAR of 4.0., Results: After 3 h only 26% of the stress activity was still present in the myocardium. SDS differences >2 were found in one (4%) patient using RSAR of 3.5, 2.5 and 2.0, in three (12%) using 1.5 and in five (20%) using SRAR of 1.0. These results were consistent with the phantom study showing SDS differences >2 for RSARs ≤1.5 and with the visual interpretation which showed an increased number of deviating scans for RSAR 1.0. Validating the RSAR of 2.0 resulted in a different SDS in one patient (SDS of 30 versus 11). Moreover, two scans were interpreted as ischemic instead of normal when using RSAR 2.0 and in two other scans the opposite was the case., Conclusions: A RSAR of 2.0 in one-day stress-first MPI SPECT seems sufficient to obtain accurate diagnostic outcomes and is therefore recommended to reduce radiation exposure.

Background: In patients with normal SPECT but persistent complaints, invasive angiography may exclude obstructive coronary disease. We assessed whether high coronary artery calcium (CAC) scores are associated with increased referral for invasive angiography following normal SPECT., Methods and Results: 2286 consecutive patients (mean age 60 ± 12, 39% male) with normal SPECT were assessed. All patients underwent simultaneous CAC scoring. Patients were categorized into four groups based on their CAC score: CAC = 0 (n = 694), CAC 1 to 100 (n = 891), CAC 101 to 400 (n = 368), and CAC >400 (n = 333). The decision to perform angiography was left to the discretion of treating physician. Follow-up angiography was confined to the first 60 days after SPECT. Occurrence of MACE (late revascularization, myocardial infarction or death) was recorded. Overall, 100 patients (4.4%) underwent early angiography with increasing rates in higher CAC score groups (1.0%, 2.6%, 8.4%, and 11.7%), respectively, P < .001). A CAC score >400 (OR 3.56, 95% CI 2.19 to 5.77, P < .001) was independently associated with referral to angiography. Similarly, CAC score >400 was an independent predictor for MACE (HR 9.26, 95% CI 5.06 to 16.93). Early angiography did not influence prognosis (HR 1.57, 95% CI 0.91 to 2.73)., Conclusions: CAC scoring impacts clinical decision-making and increases referral rates for invasive angiography after normal SPECT.

Aims: Single-photon emission computed tomography (SPECT) is widely used for the assessment of coronary artery disease and for decision making regarding revascularization. Concerns about possible false negative findings exist. Our aim was to assess the prevalence of stenoses which are both functionally and anatomically significant in patients referred for invasive fractional flow reserve (FFR) measurements following a normal SPECT, because of persistent complaints., Methods and Results: One hundred and thirty-three consecutive patients with normal SPECT were included, with a total of 180 FFR measurements. Luminal narrowing of ≥70% (≥50% for left main) together with a FFR ≤0.80 denoted an anatomically and functionally significant coronary artery stenosis. Separate analyses were performed for FFR <0.75. Mean age of the patients was 65, 40% were women. Sixteen percent of the study population had both anatomically and functionally significant stenoses. Besides the use of nitrate, no differences in baseline characteristics, symptoms, coronary history, or pre-test likelihood could be identified for the prediction of functionally relevant obstructive coronary disease. If FFR <0.75 was used, only 7.5% of the patients had both anatomically and functionally significant stenoses., Conclusion: In patients with normal SPECT who undergo FFR measurements because of persistent complaints, the prevalence of stenoses which are both anatomically and functionally significant is low. This suggests that the prevalence of false-negative SPECT is (very) low.

Background: Correction of motion has become feasible on cadmium-zinc-telluride (CZT)-based SPECT cameras during myocardial perfusion imaging (MPI). Our aim was to quantify the motion and to determine the value of automatic correction using commercially available software., Methods and Results: We retrospectively included 83 consecutive patients who underwent stress-rest MPI CZT-SPECT and invasive fractional flow reserve (FFR) measurement. Eight-minute stress acquisitions were reformatted into 1.0- and 20-second bins to detect respiratory motion (RM) and patient motion (PM), respectively. RM and PM were quantified and scans were automatically corrected. Total perfusion deficit (TPD) and SPECT interpretation-normal, equivocal, or abnormal-were compared between the noncorrected and corrected scans. Scans with a changed SPECT interpretation were compared with FFR, the reference standard. Average RM was 2.5 ± 0.4 mm and maximal PM was 4.5 ± 1.3 mm. RM correction influenced the diagnostic outcomes in two patients based on TPD changes ≥7% and in nine patients based on changed visual interpretation. In only four of these patients, the changed SPECT interpretation corresponded with FFR measurements. Correction for PM did not influence the diagnostic outcomes., Conclusion: Respiratory motion and patient motion were small. Motion correction did not appear to improve the diagnostic outcome and, hence, the added value seems limited in MPI using CZT-based SPECT cameras.

Background: SPECT Myocardial perfusion imaging (MPI) is associated with a relatively high radiation burden and decreasing image quality in heavy patients. Patient-specific low-activity protocols (PLAPs) are suggested but follow-up data is lacking. Our aim was to compare the use of a standard fixed-activity protocol (FAP) with a PLAP in cadmium zinc telluride (CZT)-SPECT MPI., Methods: We retrospectively included 1255 consecutive patients who underwent CZT-SPECT stress-optional rest MPI. 668 Patients were scanned using FAP (370 MBq) and 587 patients using PLAP (2.25 MBq·kg -1 ). Percentage of scans interpreted as normal, radiation dose, and 1-year follow-up including hard event rates (all-cause death or non-fatal myocardial infarction) were collected and compared., Results: The percentage of scans interpreted as normal was 67% in FAP and 70% in PLAP groups (P = .29). The annualized hard event rates in these patients were 1.0% in the FAP and 0.9% in the PLAP group (P = .86). However, the mean radiation dose decreased by 23% for stress-only and by 15% to 2.6 mSv for stress-optional rest MPI after introduction of the PLAP (p<0.001)., Conclusions: Introduction of a patient-specific low-activity protocol does not affect the percentage of scans interpreted as normal or prognosis but significantly lowers the radiation dose for CZT-SPECT MPI.

The prognostic value of myocardial perfusion imaging (MPI) with the cadmium-zinc-telluride (CZT) SPECT camera is not well established. Therefore, the aim of the current study was to evaluate the prognostic value of MPI performed with a CZT SPECT camera in a large cohort of patients suspected of having coronary artery disease. Methods: Consecutive symptomatic stable patients ( n = 4,057) without a history of coronary artery disease underwent CZT SPECT MPI. During a median follow-up of 2.4 y (25th-75th percentile, 1.7-3.4), patients were monitored for primary (nonfatal myocardial infarction and cardiac mortality) and secondary outcomes (late revascularization [>90 d after scanning] and primary outcome). Results: Patients with normal perfusion demonstrated low annual event rates (primary outcome, 0.2%; secondary outcome, 0.6%). Annual event rates increased with the extent of abnormality of myocardial perfusion. In patients with small ischemic perfusion defects, annual event rates were 0.7% and 2.8% for the primary and secondary outcome, respectively. In patients with moderate or large ischemic perfusion defects, these event rates were 1.2% and 4.3%, respectively. After multivariate analysis, the risk for events was significantly associated with the extent of ischemia (hazard ratio for small ischemic defects: 2.2, 95% confidence interval [CI], 0.9-5.9 and 4.6, 95% CI, 2.8-7.6, for primary and secondary outcomes, respectively; hazard ratio for moderate or large ischemic defects: 4.0, 95% CI, 1.5-10.5 and 12.1, 95% CI, 7.2-20.2, for primary and secondary outcomes, respectively). Conclusion: Our findings show that MPI acquired with a CZT SPECT camera provides excellent prognostic information, with low event rates in patients with normal myocardial perfusion. In patients with abnormal SPECT MPI, the extent of abnormality is independently associated with an increased risk of events., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Attenuation correction (AC) improves the diagnostic outcome of stress-only myocardial perfusion imaging (MPI) using conventional SPECT. Our aim was to determine the value of AC using a cadmium zinc telluride-based (CZT)-SPECT camera., Methods and Results: We retrospectively included 107 consecutive patients who underwent stress-optional rest MPI CZT-SPECT/CT. Next, we created three types of images for each patient; (1) only displaying reconstructed data without the CT-based AC (NC), (2) only displaying AC, and (3) with both NC and AC (NC + AC). Next, two experienced physicians visually interpreted these 321 randomized images as normal, equivocal, or abnormal. Image outcome was compared with all hard events over a mean follow-up time of 47.7 ± 9.8 months. The percentage of images interpreted as normal increased from 45% using the NC images to 72% using AC and to 67% using NC + AC images (P < .001). Hard event hazard ratios for images interpreted as normal were not different between using NC and AC (1.01, P = .99), or NC and NC + AC images (0.97, P = .97)., Conclusions: AC lowers the need for additional rest imaging in stress-first MPI using CZT-SPECT, while long-term patient outcome remained identical. Use of AC reduces the need for additional rest imaging, decreasing the mean effective dose by up to 1.2 mSv.

Objectives: To investigate the impact of left bundle branch block (LBBB) on sequential single photon emission computed tomography (SPECT)/ CT imaging starting with stress-first SPECT., Methods: Consecutive symptomatic low- to intermediate-risk patients without a history of coronary artery disease (CAD) referred for SPECT/CT were included from an observational registry. If stress SPECT was abnormal, additional rest SPECT and, if feasible, coronary CT angiography (CCTA) were acquired., Results: Of the 5,018 patients, 218 (4.3 %) demonstrated LBBB. Patients with LBBB were slightly older than patients without LBBB (65±12 vs. 61±11 years, p<0.001). Stress SPECT was more frequently abnormal in patients with LBBB (82 % vs. 46 %, p<0.001). After reviewing stress and rest images, SPECT was normal in 43 % of the patients with LBBB, compared to 77 % of the patients without LBBB (p<0.001). Sixty-four of the 124 patients with LBBB and abnormal stress-rest SPECT underwent CCTA (52 %), which could exclude obstructive CAD in 46 of the patients (72 %)., Conclusions: Sequential SPECT/CT imaging starting with stress SPECT is not the optimal imaging protocol in patients with LBBB, as the majority of these patients have potentially false-positive stress SPECT. First-line testing using CCTA may be more appropriate in low- to intermediate-risk patients with LBBB., Key Points: • Stress-first SPECT imaging is attractive if many patients demonstrate normal stress perfusion. • The majority of left bundle branch block patients have abnormal stress-first SPECT. • Coronary CT excluded obstructive CAD in many LBBB patients with abnormal SPECT. • Stress-first SPECT imaging is not the optimal imaging protocol in LBBB patients. • In LBBB patients imaging with initial coronary CT may be more appropriate.

Hybrid cardiac SPECT-CT is a technique in which data from both nuclear single photon emission tomography (SPECT) and a CT scan are combined. These techniques are complementary to each other, as CT provides information about anatomy of coronary arteries (stenosis, calcification, aberrant vessels) while SPECT detects functional consequences such as myocardial ischemia. In 2009, the Isala Hospital in Zwolle (the Netherlands) was one of the first centres in Europe to introduce this technique. Hybrid cardiac SPECT-CT has proved to be effective and safe in reaching a comprehensive diagnosis and gives the physician the ability to reach a diagnosis in only one day. In addition, it has led to about 20% fewer invasive coronary angiograms. Utilising this technique requires close collaboration between cardiologists and nuclear medicine specialists.

The coronary artery calcium (CAC) score provides independent prognostic value on top of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). We sought to determine whether the prognostic value of the CAC score in patients with normal SPECT MPI is gender specific. We studied 3,705 consecutive symptomatic patients without a history of coronary artery disease with normal SPECT MPI. All patients underwent concomitant CAC scoring, which was categorized as CAC score 0, 1 to 99, 100 to 399, 400 to 999, or ≥1,000. Major adverse cardiac events were defined as revascularization, nonfatal myocardial infarction, or all-cause mortality. The median CAC score was 9 in women (interquartile range 0 to 113) and 47 in men (interquartile range 1 to 307, p <0.001). The annual event rate was lower in women than in men (1.6% and 2.7%, respectively, p <0.001). When stratified by CAC score, annual event rates were similar (for women and men, respectively: CAC score 0, 0.6% and 0.5%, p = 0.95; CAC score 1 to 99, 0.9% and 1.2%, p = 0.45; CAC score 100 to 399, 2.7% and 3.8%, p = 0.23; CAC score 400 to 999, 3.8% and 5.3%, p = 0.34; CAC score ≥1,000, 8.4% and 8.7%, p = 0.99). The CAC score was an independent predictor of major adverse cardiac events in both genders (CAC score ≥1,000: hazard ratio for women 8.5, 95% confidence interval 4.0 to 18.1; hazard ratio for men 14.8, 95% confidence interval 5.3 to 41.1). In conclusion, risk for events is similar for both genders when stratified by CAC score, wherein a high CAC score carries a high risk for events despite normal SPECT MPI. Our findings do not reveal a gender-specific prognostic value of the CAC score., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Single photon emission computed tomography (SPECT) myocardial perfusion imaging has proven to have prognostic importance in patients with suspected stable coronary artery disease (CAD). The recently introduced ultrafast cadmium zinc telluride (CZT)-based gamma cameras have been associated with less equivocal findings and more normal interpretations, allowing stress-only imaging to be performed more often. However, it is yet unclear whether normal stress-only CZT SPECT has comparable prognostic value as normally interpreted stress-only conventional SPECT., Methods: The study population consisted of 1,650 consecutive patients without known CAD with normal stress-only myocardial perfusion results with either conventional (n = 362) or CZT SPECT (n = 1,288). The incidence of major adverse cardiac events (MACE, all-cause death, non-fatal myocardial infarction and/or coronary revascularization) was compared between the conventional SPECT and CZT SPECT groups. Multivariable analyses using the Cox model were used to adjust for differences in baseline variables., Results: Patients scanned with CZT were less often male (33 vs 39 %), had less often hypercholesterolaemia (41 vs 50 %) and had more often a family history of CAD (57 vs 49 %). At a median follow-up time of 37 months (interquartile range 28-45 months) MACE occurred in 68 patients. The incidence of MACE was 1.5 %/year in the CZT group, compared to 2.0 %/year in the conventional group (p = 0.08). After multivariate analyses, there was a trend to a lower incidence of MACE in the CZT SPECT group (hazard ratio 0.61, 95 % confidence interval 0.35-1.04, p = 0.07)., Conclusion: The prognostic value of normal stress-only CZT SPECT is at least comparable and may be even better than that of normal conventional stress SPECT.

Background: The decreasing image quality in heavier patients can be compensated by administration of a patient-specific dose in myocardial perfusion imaging (MPI) using a cadmium zinc telluride-based SPECT camera. Our aim was to determine if the same can be achieved when using a conventional SPECT camera., Methods: 148 patients underwent SPECT stress MPI using a fixed Tc-99m tetrofosmin tracer dose. Measured photon counts were normalized to administered tracer dose and scan time and were correlated with body weight, body mass index, and mass per length to find the best predicting parameter. From these data, a protocol to provide constant image quality was derived, and subsequently validated in 125 new patients., Results: Body weight was found to be the best predicting parameter for image quality and was used to derive a new dose formula; A admin (MBq) = 223·body weight (kg)(0.65)/T scan (min). The measured photon counts decreased in heavier patients when using a fixed dose (P < .01) but this was no longer observed after applying a body-weight-dependent protocol (P = .20)., Conclusions: Application of a patient-specific protocol resulted in an image quality less depending on patient's weight. The results are most likely independent of the type of SPECT camera used, and, hence, adoption of patient-specific dose and scan time protocols is recommended.

Unlabelled: Myocardial perfusion imaging (MPI) with SPECT is widely adopted in clinical practice but is associated with a relatively high radiation dose. The aim of this study was to determine the minimum product of tracer dose and scan time that will maintain diagnostic value for cadmium zinc telluride (CZT) SPECT MPI., Methods: Twenty-four patients underwent clinically indicated stress MPI using CZT SPECT and a body weight-dependent (3 MBq/kg) (99m)Tc-tetrofosmin tracer dose. Data were acquired for 8 min in list mode. Next, images were reconstructed using 2-, 4-, 6-, and 8-min time frames. Differences between the 8-min reference scan and the shorter scans were determined in segmental uptake values (using the 17-segment cardiac model), ejection fraction, and end-diastolic volume. A 5% difference in segmental uptake was considered to significantly influence the diagnostic value. Next, the quality of the 4-, 6-, and 8-min scans was scored on a 4-point scale by consensus by 3 experienced nuclear medicine physicians. The physicians did not know the scan time or patient information., Results: Differences in segmental uptake values, ejection fraction, and end-diastolic volume were greater for shorter scans than for the 8-min reference scan. On average, the diagnostic value was influenced in 7.7 segments per patient using the 2-min scans, in comparison to 2.0 and 0.8 segments per patient using the 4- and 6-min scans, respectively. In addition, the 4-min scans led to a significantly reduced image quality compared with the 8-min scans (P < 0.05). This was not the case for the 6-min scan., Conclusion: Six minutes was the shortest acquisition time in stress MPI using CZT SPECT that did not affect the diagnostic value for a tracer dose of 3 MBq/kg. Hence, the patient-specific product of tracer dose and scan time can be reduced to a minimum of 18 MBq·min/kg, which may lower the effective radiation dose for patients to values below 1 mSv., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Proton-pump inhibitors (PPIs) induce potentially interfering stomach wall activity in single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) with technetium-99m ((99m)Tc)-sestamibi. However, no data are available for (99m)Tc-tetrofosmin. We assessed the influence of prolonged (>2 weeks) PPI use on the stomach wall uptake of (99m)Tc-tetrofosmin in patients referred for stress MPI with a cadmium-zinc-telluride-based SPECT camera and its relation with dyspepsia symptoms., Methods and Results: Consecutive patients (n=127) underwent a 1-day adenosine stress-first SPECT-MPI with (99m)Tc-tetrofosmin, of whom 54 (43%) patients had been on PPIs for more than 2 weeks. Stomach wall activity was identified on stress SPECT using computed tomographic attenuation maps and was scored using a four-point grading scale into clinically relevant (scores 2 or 3) or nonrelevant (scores 0 or 1).Patients on PPIs had stomach wall uptake more frequently as compared with patients not using PPIs (22 vs. 7%, P=0.017). Dyspepsia was similar in both groups., Conclusion: Prolonged use of PPIs is associated with stomach wall uptake of (99m)Tc-tetrofosmin in stress cadmium-zinc-telluride-SPECT images. Gastric symptoms were not associated with stomach wall uptake.

Background: The new multipinhole cardiac single photon emission computed tomography/computed tomography (SPECT/CT) cameras with cadmium-zinc-telluride (CZT) detectors are highly sensitive and produce images of high quality but rely on complex dedicated reconstruction algorithms. The aim of this study was to determine the impact of various processing steps on image formation and in the detection of ischaemia in CZT-SPECT/CT both with and without attenuation correction (AC)., Materials and Methods: Data on 20 consecutive patients who underwent a 1-day protocol stress-rest SPECT/CT using 99mTc-tetrofosmin were processed twice by three experienced operators, yielding 120 AC and 120 noncorrected (NC) data sets. Processing steps included selection and determination of myocardial axes, manual SPECT/CT coregistration for AC and myocardial masking. Using the 17-segment cardiac model, differences between stress and rest segmental uptake (%) were calculated for NC and AC image sets. Both interoperator and intraoperator variations were considered significant for the diagnosis of ischaemia when greater than 5%., Results: The mean interoperator variations were 2.4±1.4% (NC) and 3.8±1.9% (AC) (P<0.01). In 6% (NC) and 23% (AC) of the 120 processed cases, operator variation was larger than 5% and therefore potentially clinically interfering with the diagnosis of ischaemia. Differences between interoperator and intraoperator variations were nonsignificant., Conclusion: Operator variations in the processing of myocardial perfusion image data using CZT-SPECT/CT are significant and may influence the diagnosis of ischaemia, especially when AC is applied. Clearer guidelines for image processing are necessary to improve the reproducibility of the studies and to obtain a more reliable diagnosis of ischaemia.

Background: Guidelines for SPECT myocardial perfusion imaging (MPI) traditionally recommend a fixed tracer dose. Yet, clinical practice shows degraded image quality in heavier patients. The aim was to optimize and validate the tracer dose and scan time to obtain a constant image quality less dependent on patients' physical characteristics., Methods: 125 patients underwent Cadmium Zinc Telluride (CZT)-SPECT stress MPI using a fixed Tc-99m-tetrofosmin tracer dose. Image quality was scored by three physicians on a 4-point grading scale and related to the number of photon counts normalized to tracer dose and scan time. Counts were correlated with various patient-specific parameters dealing with patient size and weight to find the best predicting parameter. From these data, a formula to provide constant image quality was derived, and subsequently tested in 92 new patients., Results: Degradation in image quality and photon counts was observed for heavier patients for all patients' specific parameters (P < .01). We found body weight to be the best-predicting parameter for image quality and derived a new dose formula. After applying this new body weight-depended tracer dose and scan time in a new group, image quality was found to be constant (P > .19) in all patients., Conclusions: Also in CZT SPECT image quality decreases with weight. The use of a tracer dose and scan time that depends linearly on patient's body weight corrected for the varying image quality in CZT-SPECT MPI. This leads to better radiation exposure justification.

Objective: Regadenoson is a recently approved selective adenosine-2A receptor agonist to induce pharmacological stress in myocardial perfusion imaging (MPI) procedures using a single bolus injection., Material and Methods: We included 123 patients referred for MPI because of suspected coronary arterial disease (CAD). Of these, 66 patients underwent a regadenoson stress test and 57 patients underwent an adenosine stress test preceding standard myocardial SPECT imaging. Technicians, physicians and patients were asked to report their experience using questionnaires., Results: As compared to adenosine, regadenoson did not produce any atrio-ventricular block (0 vs. 10% with adenosine), but did produce minor tachycardia and minimal blood pressure changes while all other side effects were milder and shorter. There were fewer patients with severe complaints after taking regadenoson than adenosine (17% vs. 32%, respectively, p<0.01). The most frequent complaint reported was dyspnea, followed by flushing and chest pain. However, when they did occur, they usually disappeared rapidly. The overall symptom score, including severity and duration of side effects, was significantly lower after regadenoson than after adenosine (6.7±6.3 vs. 10.0±7.9, respectively; p<0.01.) SPECT imaging results were similar. The regadenoson procedure was faster and more practical., Conclusion: Regadenoson, the new selective adenosine-2A receptor agonist, is a stress agent for MPI with a patient- and department friendly profile., (Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.)

Background: False-negative myocardial perfusion imaging (MPI) can by due to left main (LM) or three-vessel disease causing "balanced ischemia". However, so far prevalence of LM or three-vessel-disease in patients with normal MPI is unclear. We assessed prevalence, location, and extent of significant coronary artery disease (CAD) in patients with normal MPI., Methods: Between 2006 and 2010, 256 patients with normal MPI who had invasive angiography because of persisting or worsening of the same initial symptoms were studied. Significant CAD was defined as stenosis > 70% or LM > 50%., Results: A total of 93 patients (36%) had significant CAD. Significant CAD was observed more frequently in males, higher age and those with typical angina complaints. Significant LM disease was present in 7%, three-vessel disease in 10%, two-vessel disease in 22%, and single vessel disease (not left main) in 61%. In those with single vessel disease, the location was the LAD in 40%, the RCA in 30%, and the LCX in 30%., Conclusions: In selected patients with normal MPI, one-third had significant CAD. The majority of these patients had single vessel disease (not left main). LM or three vessel disease, causing "balanced ischemia", is a less common cause of false-negative MPI.

Purpose: Coronary artery calcium (CAC) scores influence the pre-test likelihood of ischemia in patients undergoing myocardial perfusion imaging (MPI). We investigated the influence of CAC score knowledge on the visual interpretation of MPI in patients referred for the diagnostic work-up of suspected coronary artery disease., Methods: We retrospectively analyzed symptomatic patients who were referred for MPI. For the current analysis, we selected 151 patients who underwent SPECT MPI with simultaneous CAC scoring. MPI was visually interpreted in two separate sessions, first without and then with knowledge of the CAC score. MPI results were classified into four groups: normal, fixed defects, ischemia, and equivocal., Results: Mean age of the patients was 64 ± 11 years, 56% were male. Without knowledge of the CAC score MPI was evaluated as normal in 36%, compared to 40% with knowledge of the CAC score (P = 0.636). Overall, the addition of the CAC score changed the interpretation of MPI in 56 patients (37%). Importantly, the frequency of equivocal MPI interpretations decreased from 21% without knowledge of CAC score to 9% with knowledge of CAC score (P = 0.002)., Conclusions: Knowledge of the CAC score has a major impact on the interpretation of MPI, increasing the interpretative certainty.

Purpose: The new ultrafast cardiac single photon emission computed tomography (SPECT) cameras with cadmium-zinc-telluride (CZT)-based detectors are faster and produce higher quality images as compared to conventional SPECT cameras. We assessed the need for additional imaging, total imaging time, tracer dose and 1-year outcome between patients scanned with the CZT camera and a conventional SPECT camera., Methods: A total of 456 consecutive stable patients without known coronary artery disease underwent myocardial perfusion imaging on a hybrid SPECT/CT (64-slice) scanner using either conventional (n = 225) or CZT SPECT (n = 231). All patients started with low-dose stress imaging, combined with coronary calcium scoring. Rest imaging was only done when initial stress SPECT testing was equivocal or abnormal. Coronary CT angiography was subsequently performed in cases of ischaemic or equivocal SPECT findings. Furthermore, 1-year clinical follow-up was obtained with regard to coronary revascularization, nonfatal myocardial infarction or death., Results: Baseline characteristics were comparable between the two groups. With the CZT camera, the need for rest imaging (35 vs 56%, p < 0.001) and additional coronary CT angiography (20 vs 28%, p = 0.025) was significantly lower as compared with the conventional camera. This resulted in a lower mean total administered isotope dose per patient (658 ± 390 vs 840 ± 421 MBq, p < 0.001) and shorter imaging time (6.39 ± 1.91 vs 20.40 ± 7.46 min, p < 0.001) with the CZT camera. After 1 year, clinical outcome was comparable between the two groups., Conclusion: As compared to images on a conventional SPECT camera, stress myocardial perfusion images acquired on a CZT camera are more frequently interpreted as normal with identical clinical outcome after 1-year follow-up. This lowers the need for additional testing, results in lower mean radiation dose and shortens imaging time.

Purpose: Diagnosing Parkinson's disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls., Methods: Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated., Results: FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques., Conclusion: FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity.

Purpose: Diagnosis of Parkinson's disease (PD) can be difficult. F-DOPA PET is able to quantify striatal dopa decarboxylase activity and storage capacity of F-dopamine, but is expensive and not generally available. FP-CIT binds to the dopamine transporter, and FP-CIT SPECT is cheaper and more widely available, but has a lower resolution. The aim of this study was to compare these two methods in the same patients with different stages of PD to assess their power in demonstrating deficits of the striatal dopaminergic system., Methods: Thirteen patients with de novo PD and 17 patients with advanced PD underwent FP-CIT SPECT and static F-DOPA PET. After data transfer to standard stereotactic space, a template with regions of interest was used to sample values of the caudate, putamen and an occipital reference region. The outcome value was striato-occipital ratios. Patients were clinically examined in the "off state" (UPDRS-III and H&Y stage)., Results: Good correlations were found between striatal F-DOPA uptake and striatal FP-CIT uptake (r = 0.78) and between putaminal F-DOPA uptake and putaminal FP-CIT uptake (r = 0.84, both p < 0.0001). Both striatal uptake of FP-CIT and that of F-DOPA correlated moderately with H&Y stage (rho = -0.52 for both techniques), UPDRS-III (rho = -0.38 for F-DOPA; rho = -0.45 for FP-CIT) and disease duration (rho = -0.59 for F-DOPA; rho = -0.49 for FP-CIT, all p < 0.05)., Conclusion: FP-CIT values correlate well with F-DOPA values. Both methods correlate moderately with motor scores and are equally able to distinguish patients with advanced PD from patients with de novo PD.

The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with sufficient viable myocardium, patients with predominantly scar tissue should be treated medically. Patients with left ventricular dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischemia but at the same time benefit most from revascularization. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy (SPECT), whether using (201)thallium, (99m)Tc-sestamibi, or (99m)Tc-tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management. Metabolic and perfusion imaging with positron emission tomography (PET) radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularization. New techniques in the nuclear cardiology field, like attenuation corrected SPECT, dual isotope simultaneous acquisition (DISA) SPECT and gated FDG PET are promising and will further improve the detection of myocardial viability. Also the combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and non-invasive coronary angiography to myocardial perfusion imaging and quantification. Evaluation of the clinical role of these creative new possibilities warrants investigation.

Purpose: Dual-isotope simultaneous acquisition (DISA) single-photon emission computed tomography (SPECT) is an attractive technique as it permits assessment of both myocardial glucose metabolism and perfusion within a single session, but few data on its accuracy for the assessment of viability are available as yet. In the present study, DISA SPECT was compared with positron emission tomography (PET) for the detection of myocardial viability in normal and dysfunctional left ventricular (LV) myocardium., Methods: Fifty-eight patients with chronic coronary artery disease and LV dysfunction (LV ejection fraction 33+/-12%) were studied. Patients underwent a 1-day dipyridamole stress 99mTc-sestamibi/18F-fluorodeoxyglucose (18FDG) DISA SPECT and 13N-ammonia/18FDG PET protocol. Within 1 week, resting MRI was performed to assess contractile function. Comparison of PET and SPECT data was performed using both visual and quantitative analysis., Results: The correlation of normalised activities of the flow tracers 99mTc-sestamibi and 13N-ammonia was good (r = 0.82; p < 0.001). The correlation between the two 18FDG studies was also good (r = 0.83; p < 0.001). The agreement for the assessment of viability for all segments between DISA SPECT and PET was 82%, with a kappa-statistic of 0.59 (95% CI 0.53-0.64), without a significant difference; in dysfunctional segments only, the agreement was 82%, with a kappa-statistic of 0.63 (95% CI 0.56-0.70), without a significant difference. When the DISA SPECT data were analysed visually, the agreement between DISA SPECT and PET was 83%, with a kappa-statistic of 0.58 (95% CI 0.52-0.63), without a significant difference. Moreover, there was no significant difference between visual and quantitative DISA SPECT analysis for the detection of viability., Conclusion: This study shows an overall good agreement between 99mTc-sestamibi/18FDG DISA SPECT and PET for the assessment of myocardial viability in patients with severe LV dysfunction. Quantitative or visual analysis of the SPECT data did not influence the agreement with PET, suggesting that visual assessment may be sufficient for clinical purposes.

Planar gated blood-pool imaging (GBPI) is a standard method for non-invasive assessment of left ventricular (LV) function. Gated blood-pool single photon emission computed tomographic (GBPS) data acquisition can be accomplished in the same time as GBPI, with the benefit of enabling visualization of all cardiac chambers simultaneously. The purpose of this investigation was to evaluate the degree to which automated and manual LVEF calculations agree with one another and with conventional GBPI LVEF measurements. GBPI studies were performed in 22 consecutive, unselected patients, followed by GBPS data acquisition. GBPS left ventricular ejection fraction (LVEF) calculations were performed by available software (NuSMUGA, Northwestern University, Chicago, IL) automatically and manually, using all LV gated short axis slices. Automatic LVEF assessed by GBPS correlated well with conventional planar GBPI (r = 0.88, P < 0.001). Mean planar GBPI LVEF was 50% +/- 12%, and mean GBPS automatic LVEF was significantly lower at 45% + 14% (P = 0.001), with a mean difference of 6% +/- 5%. Manual GBPS LVEF also correlated well with conventional planar GBPI (r = 0.90, P < 0.0001). Mean LVEF measurement by manual GBPS versus GBPI was significantly higher at 59% +/- 13%, with a mean difference of 10% +/- 6% (P < 0.001). Manual GBPS LVEF values were also significantly higher than automatically determined GBPS LVEF values (P < 0.001). It is concluded that LVEF values assessed by NuSMUGA GBPS software were reproducible, and automatic and manual values correlated well with conventional GBPI values. However, both automatic and manual GBPS calculations were significantly different from one another and from GBPI values, so that GBPI and NuSMUGA calculations cannot be considered to be equivalent.

Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-sestamibi ( Tc-MIBI) and metabolism using F-fluorodeoxyglucose ( F-FDG) in a single study. The prerequisite is that the Tc-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered Tc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-MIBI and 185 MBq of F-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-FDG and Tc-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r =0.93, P<0.0001) between the Tc-MIBI uptake detected in the single and dual isotope acquisition. The average difference between the dual and single isotope Tc-MIBI uptake was -1.2% (not significantly different from zero) and the coefficient of variation of the difference was 8.7%. Of the 79 regions with irreversible perfusion defects on previous rest-stress Tc-MIBI, six regions in five patients showed a perfusion-metabolism mismatch pattern. We conclude that DISA does not affect the quality of the Tc-MIBI images. Furthermore, F-FDG- Tc-MIBI DISA may show viability in a small but significant (7.6%, P<0.0034) number of regions with irreversible perfusion defects on rest-stress Tc-MIBI.

Unlabelled: L-3-[123I]iodo-alpha-methyl-tyrosine (IMT) is a modified amino acid that is avidly taken up by many tumors. Uptake is based on the increased transmembrane transport of amino acids in malignancies. IMT is the only amino acid tracer suitable for SPECT. The aim of this study was to determine the feasibility of IMT SPECT in the detection, staging, and treatment evaluation of non-small cell lung cancer., Methods: We evaluated 44 IMT SPECT studies in 17 patients with histologically proven non-small cell lung cancer, stage III. IMT SPECT and planar imaging of the chest was performed before, 2 wk after, and 3 mo after 60 Gy radiotherapy. Staging was based on the findings of bronchoscopy, chest CT, mediastinoscopy, or explorative thoracotomy. After radiotherapy, CT and bronchoscopy were repeated to assess tumor response., Results: In 15 of 16 evaluable primary tumors, avid IMT uptake was present (sensitivity, 94%), with a mean (+/-SD) tumor-to-background ratio (T/B) of 2.95 +/- 0.78 (range, 1.7-4.9). In 12 of 14 patients (86%) with mediastinal involvement, IMT SPECT detected one or more mediastinal metastases. However, only 13 of 20 mediastinal metastases were detected in lesion analysis (lesion-based sensitivity, 65%). For lesions < 2 cm in diameter, sensitivity was 42%. FDG PET (available for 5 patients) detected more known and unknown lesions than did IMT SPECT. After radiotherapy, T/B had fallen to 1.84 +/- 0.29 (P < 0.001 vs. baseline), and 3 mo later to 1.61 +/- 0.41 (not statistically significant vs. second study). Considerable nonspecific uptake was found in irradiated normal lung tissue (mean ratio to nonirradiated tissue, 1.79 +/- 0.53), persisting for > 3 mo. No relationship was observed between various IMT uptake parameters and the presence of residual viable tumor tissue or survival., Conclusion: IMT SPECT has a high sensitivity for the detection of primary non-small cell lung cancer. Although patient-based sensitivity in detecting mediastinal spread was adequate, sensitivity for individual lesions, especially for small metastases (<2 cm in diameter) was too low to be clinically helpful. Radiotherapy caused considerable nonspecific IMT uptake, which also limits applicability in evaluating the results of treatment.

Objectives: We sought to prospectively compare nitrogen-13 (13N)-ammonia/18fluorodeoxyglucose (18FDG) positron emission tomography (PET)-guided management with stress/rest technetium-99m (99mTc)-sestamibi single-photon emission computed tomography (SPECT)-guided management., Background: Patients with evidence of jeopardized (i.e., ischemic or viable) myocardium may benefit from revascularization, whereas patients without it should be treated with drugs. Both PET and SPECT imaging have been proven to delineate jeopardized myocardium. When patient management is based on identification of jeopardized myocardium, it is unknown which technique is most accurate for long-term prognosis., Methods: In a clinical setting, 103 patients considered for revascularization with left ventricular wall motion abnormalities and suspicion of jeopardized myocardium underwent both PET and SPECT imaging. The imaging results were used in a randomized fashion to determine management (percutaneous transluminal coronary angioplasty [PTCA], coronary artery bypass graft surgery [CABG] or drug treatment). Follow-up for cardiac events (cardiac death, myocardial infarction and revascularization) was recorded for 28 +/- 1 months. The study was designed to have a power of 80% to detect a 20% difference in the event rate between PET- and SPECT-based management., Results: Management decisions in 49 patients randomized to PET (12 who had PTCA, 14 CABG and 23 drug therapy) were comparable with 54 patients randomized to SPECT (15 who had PTCA, 13 CABG and 26 drug therapy). In terms of cardiac event-free survival, no differences between PET and SPECT were observed (11 vs. 13 cardiac events for PET and SPECT, respectively; p = NS by the Kaplan-Meier statistic)., Conclusions: No difference in patient management or cardiac event-free survival was demonstrated between management based on 13N-ammonia/18FDG PET and that based on stress/rest 99mTc-sestamibi SPECT imaging. Both techniques may be used for management of patients considered for revascularization with suspicion of jeopardized myocardium.

Unlabelled: L-3-[123I]-Iodo-alpha-methyl-tyrosine (IMT) is a modified amino acid. It is reported to be avidly taken up in brain tumors, reflecting amino acid transport and is suitable for SPECT., Methods: To determine whether tumors outside the brain can also accumulate this tracer, we injected 300-450 MBq IMT into 20 patients with different tumors [5 breast cancers, 4 lung tumors (1 benign), 2 carcinoid liver metastases, 4 soft-tissue tumors (1 benign), 3 malignant lymphomas and 2 primary brain tumors]. Tumor size ranged from 1-12 cm. Imaging was repeated after radiotherapy in two patients with breast cancer. Histology was available in all cases. Dynamic scans, whole-body imaging and SPECT were performed during the first hour and 3 hr after injection. Plasma samples were analyzed for IMT, free 1231 and other metabolites., Results: All primary tumors were visualized. Tumor-to-background ratios ranged from 1.1 to 3.8 on planar and from 1.3 to 6.2 on SPECT images. Tumor uptake peaked in the first hour. Two carcinoid lesions in the liver tumors exhibited no IMT uptake above liver background. Tumor-to-background ratios in a benign bone inflammatory process and a focal pulmonary vasculitis were less than 1.2 (planar) and 1.9 (SPECT) and could be differentiated from uptake in all malignant nonbrain tumors. IMT was rapidly cleared from the plasma [3.6% +/- 0.6% (mean +/- s.d.) injected dose/liter at 10 min postinjection]. Minor in vivo deiodination was present (<1% of injected dose 1 hr postinjection). No other metabolites were found. Normal distribution consists of some uptake in the brain, liver, spleen, muscles, pancreatic region and intestinal structures and massive uptake and excretion in the kidneys and bladder., Conclusion: IMT has potential as a metabolic tracer in tumors outside the brain.