The EXERRT trial: "EXErcise to Regadenoson in Recovery Trial": A phase 3b, open-label, parallel group, randomized, multicenter study to assess regadenoson administration following an inadequate exercise stress test as compared to regadenoson without exercise for myocardial perfusion imaging using a SPECT protocol.

BACKGROUND: This study assessed the non-inferiority and safety of regadenoson administration during recovery from inadequate exercise compared with administration without exercise. METHODS: Patients unable to achieve adequate exercise stress were randomized to regadenoson 0.4 mg either during recovery (Ex-Reg) or 1 hour after inadequate exercise (Regadenoson) (MPI1). All patients also underwent non-exercise regadenoson MPI 1-14 days later (MPI2). The number of segments with reversible perfusion defects (RPDs) detected using single photon emission computerized tomography imaging was categorized. The primary analysis evaluated the majority agreement rate between Ex-Reg and Regadenoson groups. RESULTS: 1,147 patients were randomized. The lower bound of the 95% confidence interval of the difference in agreement rates (-6%) was above the -7.5% non-inferiority margin, demonstrating non-inferiority of Ex-Reg to Regadenoson. Adverse events were numerically less with Ex-Reg (MPI1). In the Ex-Reg group, one patient developed an acute coronary syndrome and another had a myocardial infarction following regadenoson after exercise. Upon review, both had electrocardiographic changes consistent with ischemia prior to regadenoson. CONCLUSIONS: Administering regadenoson during recovery from inadequate exercise results in comparable categorization of segments with RPDs and with careful monitoring appears to be well tolerated in patients without signs/symptoms of ischemia during exercise and recovery.

Patient-centered imaging: shared decision making for cardiac imaging procedures with exposure to ionizing radiation.

The current paper details the recommendations arising from an NIH-NHLBI/NCI-sponsored symposium held in November 2012, aiming to identify key components of a radiation accountability framework fostering patient-centered imaging and shared decision-making in cardiac imaging. Symposium participants, working in 3 tracks, identified key components of a framework to target critical radiation safety issues for the patient, the laboratory, and the larger population of patients with known or suspected cardiovascular disease. The use of ionizing radiation during an imaging procedure should be disclosed to all patients by the ordering provider at the time of ordering, and reinforced by the performing provider team. An imaging protocol with effective dose ≤3 mSv is considered very low risk, not warranting extensive discussion or written informed consent. However, a protocol effective dose >20 mSv was proposed as a level requiring particular attention in terms of shared decision-making and either formal discussion or written informed consent. Laboratory reporting of radiation dosimetry is a critical component of creating a quality laboratory fostering a patient-centered environment with transparent procedural methodology. Efforts should be directed to avoiding testing involving radiation, in patients with inappropriate indications. Standardized reporting and diagnostic reference levels for computed tomography and nuclear cardiology are important for the goal of public reporting of laboratory radiation dose levels in conjunction with diagnostic performance. The development of cardiac imaging technologies revolutionized cardiology practice by allowing routine, noninvasive assessment of myocardial perfusion and anatomy. It is now incumbent upon the imaging community to create an accountability framework to safely drive appropriate imaging utilization.

Regadenoson pharmacologic rubidium-82 PET: a comparison of quantitative perfusion and function to dipyridamole.

BACKGROUND: Dipyridamole is used for stress (82)rubidium chloride ((82)RbCl) PET because of its long hyperemic duration. Regadenoson has advantages of a fixed dose and favorable symptom profile, but its mean maximal hyperemia is only 2.3 minutes. To determine its suitability for (82)RbCl PET, we imaged subjects using a regadenoson protocol based on its hyperemic response and compared the images in the same subjects having dipyridamole PET. METHODS: In 32 subjects (23 M), we assessed visually by blinded interpretation and quantitatively compared summed stress and difference scores, total perfusion deficit (TPD), LVEF, LV volumes, and change in stress-rest function. Linear correlation and Bland-Altman analysis of the paired measurements were applied for evaluation of differences. Paired t test and Pearson's correlation were applied for testing of significance. RESULTS: The images were interpreted the same by visual assessment. Twenty-six (26) subjects had reversible defects; by quantitation the SSS was 12.9 ± 7.0 and 14.1 ± 6.4 (P = .23) and SDS was 7.0 ± 6.8 versus 7.6 ± 6.2 (P = .40) for dipyridamole and regadenoson, respectively. Six (6) subjects had <5% likelihood of CAD and were normal by both. All paired measurements showed a high positive correlation between regadenoson and dipyridamole; stress segmental perfusion Reg = 0.93Dip + 4.4, r = 0.88; TPD Reg = 0.94Dip + 0.41, r = 0.93; LVEF Reg = 0.92Dip + 4.7, r = 0.95; stress minus rest LVEF Reg = 0.87Dip - 0.99, r = 0.82. CONCLUSION: Regadenoson stress (82)RbCl PET perfusion defect and cardiac function measurements are visually and quantitatively equivalent to dipyridamole studies and can be obtained with the clinical advantages of regadenoson.

A multicenter evaluation of a new post-processing method with depth-dependent collimator resolution applied to full-time and half-time acquisitions without and with simultaneously acquired attenuation correction.

BACKGROUND: The field of nuclear cardiology is limited by image quality and length of procedure. The use of depth-dependent resolution recovery algorithms in conjunction with iterative reconstruction holds promise to improve image quality and reduce acquisition time. This study compared the Astonish algorithm employing depth-dependent resolution recovery and iterative reconstruction to filtered backprojection (FBP) using both full-time (FTA) and half-time (HTA) data. Attenuation correction including scatter correction in conjunction with the Astonish algorithm was also evaluated. METHODS: We studied 187 consecutive patients (132 with cardiac catheterization and 55 with low likelihood for CAD) from three nuclear cardiology laboratories who had previously undergone clinically indicated rest/stress Tc-99m sestamibi or tetrofosmin SPECT. Acquisition followed ASNC guidelines (64 projections, 20-25 seconds). Processing of the full-time data sets included FBP and Astonish (FTA). A total of 32 projection data sets were created by stripping the full-time data sets and processing with Astonish (HTA). Attenuation correction was applied to both full-time and half-time Astonish-processed images (FTA-AC and HTA-AC, respectively). A consensus interpretation of three blinded readers was performed for image quality, interpretative certainty, and diagnostic accuracy, as well as severity and reversibility of perfusion and functional parameters. RESULTS: Full-time and half-time Astonish processing resulted in a significant improvement in image quality in comparison with FBP. Stress and rest perfusion image quality (excellent or good) were 85%/80% (FBP), 98%/95% (FTA), and 95%/92% (HTA), respectively (p < 0.001). Interpretative certainty and diagnostic accuracy were similar with FBP, FTA, and HTA. Left ventricular functional data were not different despite a slight reduction in half-time gated image quality. Application of attenuation correction resulted in similar image quality and improved normalcy (FTA vs. FTA-AC: 76% vs. 95%; HTA vs. HTA-AC: 76% vs. 100%) and specificity (FTA vs. FTA-AC: 62% vs. 78%; HTA vs. HTA-AC: 63% vs. 84%) (p < 0.01 for all comparisons). CONCLUSION: Astonish processing, which incorporates depth-dependent resolution recovery, improves image quality without sacrificing interpretative certainty or diagnostic accuracy. Application of simultaneously acquired attenuation correction, which includes scatter correction, to full-time and half-time images processed with this method, improves specificity and normalcy while maintaining high image quality.

Multicenter investigation comparing a highly efficient half-time stress-only attenuation correction approach against standard rest-stress Tc-99m SPECT imaging.

BACKGROUND: New iterative algorithms for scatter compensation (SC), noise suppression, and depth-dependent collimator resolution (RR) can shorten rest and stress SPECT acquisitions by 50% while maintaining quality and accuracy equivalent to conventional scans. Full-time stress-only myocardial perfusion SPECT is accurate and efficient when combined with line-source attenuation correction (LSAC). We investigated the potential for half-time stress-only LSAC-SPECT by comparing this to conventional rest/stress SPECT in patients imaged for suspected CAD at three different centers. METHODS: One hundred and ten patients (58% men, 53% exercise) had 64 projection rest/stress Tc-99m ECG-gated SPECT with simultaneous Gd-153 LSAC: 18 had

Validation of attenuation correction using transmission truncation compensation with a small field of view dedicated cardiac SPECT camera system.

BACKGROUND: Although attenuation correction (AC) has been successfully applied to large field of view (LFOV) cameras, applicability to small field of view (SFOV) cameras is a concern due to truncation. This study compared perfusion images between a LFOV and SFOV camera with truncation compensation, using the same AC solution. METHODS AND RESULTS: Seventy-eight clinically referred patients underwent rest-stress single-photon emission computed tomography (SPECT) using both a SFOV and LFOV camera in a randomized sequence. Blinded images were interpreted by a consensus of three experienced readers. The percentage of normal images for SFOV and LFOV was significantly higher with than without AC (72% vs 44% and 72% vs 49%, both P < .001). Interpretive agreement between cameras was better with than without AC (kappa = 0.736 to 0.847 vs 0.545 to 0.774). Correlation for the summed stress score was higher with than without AC (r (2) = 0.892 vs 0.851, both P < 0.001) while Bland Altman analysis demonstrated narrower limits with than without AC (4.0 to -4.3 vs 5.9 to -5.6). CONCLUSION: Attenuation correction using truncation compensation with a SFOV camera yields similar results to a LFOV camera. The higher interpretive agreement between cameras after attenuation correction suggests that such images are preferable to non-attenuation-corrected images.

Independent and incremental prognostic value of left ventricular ejection fraction determined by stress gated rubidium 82 PET imaging in patients with known or suspected coronary artery disease.

BACKGROUND: Whether left ventricular ejection fraction (EF) obtained by gated rubidium 82 positron emission tomography (PET) myocardial imaging can identify patients at risk for future cardiac events is unclear. METHODS AND RESULTS: Consecutive patients with known or suspected coronary artery disease who underwent dipyridamole stress gated Rb-82 PET imaging were evaluated. Scoring of perfusion was accomplished by use of a 17-segment model. EF was automatically generated. Patients were stratified based on summed stress scores (SSSs) (0-3, 4-8, or >8) and stress EF (>50%, 40%-49%, or <40%). All-cause mortality was determined by use of the Social Security Death Index. Of 1,441 patients, 132 (9.2%) died during mean follow-up of 2.7 +/- 0.8 years. Annualized mortality rates across SSS groups were 2.4% for SSS of 0 to 3, 4.1% for SSS of 4 to 8, and 6.9% for SSS greater than 8 (P < .001). Similarly, annualized mortality rates were 2.4%, 6.2%, and 9.2% for the group with EF greater than 50%, group with EF of 40% to 49%, and group with EF lower than 40%, respectively (P < .001). On multivariate analysis, the addition of EF to clinical and perfusion variables significantly increased the global chi(2) (73.3 to 107.7, P < .001). Integration of EF with SSS significantly enhanced risk stratification. CONCLUSION: EF assessed by stress gated Rb-82 PET imaging provides independent and incremental prognostic information and, hence, should be routinely incorporated in risk assessment.

Reconstruction of rapidly acquired Germanium-68 transmission scans for cardiac PET attenuation correction.

BACKGROUND: Transmission (TX) scan time by use of radionuclide sources for cardiac positron emission tomography prolong imaging and increase the likelihood of patient motion artifacts. A reconstruction algorithm combining ordered-subsets expectation maximization with a Bayesian prior was developed and applied to rapid Germanium-68 (Ge-68) TX scans. METHODS AND RESULTS: A cardiac phantom with Fluorine-18 (Fl-18) was used to determine a minimal count threshold for Ge-68 TX scanning. Images were acquired over a count range from 2.5 x 10(6) to 8 x 10(7) and for a high-count scan of 1.6 x 10(9) counts to study reconstruction parameters and to determine the minimum TX count threshold. The method was compared against clinical 4-minute TX scans in ten Rubidium-82 (Rb-82) rest/stress myocardial perfusion studies (body mass index, 30 +/- 4 kg/m(2)). The minimal count threshold was 20 x 10(6), and the mean scan time for the Rb-82 studies was 70.5 +/- 3.4 seconds. More than 90% of the segmental scores computed from images acquired via rapid TX scans differed by less than 5% from those obtained with 4-minute TX scans. The mean differences in perfusion scores between the rapid and 4-minute TX scans were 0.46% (95% confidence interval, -1.84% to 0.93%) at rest and 0.39% (95% confidence interval, -1.84% to 1.07%) at stress, demonstrating equivalency of the rapid and 4-minute scans. CONCLUSIONS: Ordered-subsets expectation maximization with a Bayesian prior accurately and efficiently reconstructs rapidly acquired Ge-68 TX scans for Rb-82 myocardial perfusion positron emission tomography studies.

A Bayesian iterative transmission gradient reconstruction algorithm for cardiac SPECT attenuation correction.

BACKGROUND: High-quality attenuation maps are critical for attenuation correction of myocardial perfusion single photon emission computed tomography studies. The filtered backprojection (FBP) approach can introduce errors, especially with low-count transmission data. We present a new method for attenuation map reconstruction and examine its performance in phantom and patient data. METHODS AND RESULTS: The Bayesian iterative transmission gradient algorithm incorporates a spatially varying gamma prior function that preferentially weights estimated attenuation coefficients toward the soft-tissue value while allowing data-driven solutions for lung and bone regions. The performance with attenuation-corrected technetium 99m sestamibi clinical images was evaluated in phantom studies and in 50 low-likelihood patients grouped by body mass index (BMI). The algorithm converged in 15 iterations in the phantom studies. For the clinical studies, soft-tissue estimates had significantly greater uniformity of mediastinal coefficients (mean SD, 0.005 cm(-1) vs 0.011 cm(-1); P < .0001). The accuracy and uniformity of the Bayesian iterative transmission gradient algorithm were independent of BMI, whereas both declined at higher BMI values with FBP. Attenuation-corrected perfusion images showed improvement in myocardial wall variability (4.8% to 4.1%, P = .02) for all BMI groups with the new method compared with FBP. CONCLUSION: This new method for attenuation map reconstruction provides rapidly converging and accurate attenuation maps over a wide spectrum of patient BMI values and significantly improves attenuation-corrected perfusion images.

Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT.

BACKGROUND: Although single photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) have evolved considerably over the last decade, there is no recent comparison of diagnostic performance. This study was designed to assess relative image quality, interpretive confidence, and diagnostic accuracy by use of contemporary technology and protocols. METHODS AND RESULTS: By consensus and without clinical information, 4 experienced nuclear cardiologists interpreted 112 SPECT technetium-99m sestamibi and 112 PET rubidium-82 MPI electrocardiography (ECG)-gated rest/pharmacologic stress studies in patient populations matched by gender, body mass index, and presence and extent of coronary disease. The patients were categorized as having a low likelihood for coronary artery disease (27 in each group) or had coronary angiography within 60 days. SPECT scans were acquired on a Cardio-60 system and PET scans on an ECAT ACCEL scanner. Image quality was excellent for 78% and 79% of rest and stress PET scans, respectively, versus 62% and 62% of respective SPECT scans (both p<.05). An equal percent of PET and SPECT gated images were rated excellent in quality. Interpretations were definitely normal or abnormal for 96% of PET scans versus 81% of SPECT scans (p=.001). Diagnostic accuracy was higher for PET for both stenosis severity thresholds of 70% (89% vs 79%, p=.03) and 50% (87% vs 71%, p=.003) and was higher in men and women, in obese and nonobese patients, and for correct identification of multivessel coronary artery disease. CONCLUSION: In a large population of matched pharmacologic stress patients, myocardial perfusion PET was superior to SPECT in image quality, interpretive certainty, and diagnostic accuracy.

Transmission scan truncation with small-field-of-view dedicated cardiac SPECT systems: impact and automated quality control.

BACKGROUND: Small-field-of-view (FOV) dedicated cardiac single photon emission computed tomography (SPECT) systems will frequently exhibit severe transmission scan truncation that may degrade attenuation correction (AC). This study evaluated the impact of transmission scan truncation on AC and developed automated transmission scan truncation quality control (ATSTQC) for small-FOV systems. METHODS AND RESULTS: Small-FOV data were simulated from the data of 10 patients acquired by a full-FOV Philips Vertex system. AC images of the full- and small-FOV data were compared by mean and maximum absolute differences of myocardial counts, and differences in stress and rest severity scores were calculated by use of the Emory Cardiac Toolbox.small-FOV systems. ATSTQC was developed to identify critical truncation that significantly increased these indices and then tested with 18 independent patients. Left-side truncation resulted in significant distortion of the quantitative indices. ATSTQC, developed on the condition that left-side truncation is critical, showed high concordance with the qualitative assessment in identification of critical truncation. CONCLUSIONS: Identification of left-side truncation as critical truncation is necessary to judge whether accurate AC can be obtained. The developed ATSTQC can accurately detect critical truncation and will help clinicians decide whether to use AC in a particular study.

Value of attenuation correction on ECG-gated SPECT myocardial perfusion imaging related to body mass index.

BACKGROUND: Obesity is a growing problem in the United States, and attenuation artifacts are more prevalent in this patient group. This study evaluated the impact of attenuation correction in patients with a high body mass index (BMI). METHODS AND RESULTS: Three readers interpreted gated attenuation-corrected and non-attenuation-corrected rest/stress technetium 99m sestamibi myocardial perfusion imaging results in 116 patients (BMI <30, n = 60; BMI > or =30, n = 56) who had coronary angiography no more than 60 days after imaging. Readers were blinded to all clinical information and as to whether myocardial perfusion imaging was attenuation-corrected or non-attenuation-corrected. Sensitivity, specificity, and accuracy for detection of coronary artery disease of 70% or greater for attenuation-corrected versus non-attenuation-corrected single photon emission computed tomography (SPECT) were 86% versus 89%, 79% versus 50%, and 84% versus 79%, respectively. Sensitivity, specificity, and accuracy for attenuation-corrected versus non-attenuation-corrected SPECT for patients with BMI less than 30 were 90% versus 90%, 82% versus 64%, and 88% versus 85%, respectively. For BMI of 30 or greater, the results were 82% versus 87%, 76% versus 41%, and 80% versus 73%, respectively. There was a significant difference in specificity overall ( P = .02) and for the category of BMI of 30 or greater ( P = .03). CONCLUSIONS: This study demonstrates that electrocardiography-gated attenuation-corrected Tc-99m sestamibi SPECT myocardial perfusion imaging improves specificity compared with electrocardiography-gated non-attenuation-corrected SPECT myocardial perfusion imaging, especially in patients with BMI of 30 or greater.

Attenuation correction single-photon emission computed tomography myocardial perfusion imaging.

Clinicians now rely heavily on the results of single-photon emission computed tomography (SPECT) myocardial perfusion imaging for diagnosing coronary disease and for planning therapy. However, the technique is imperfect for these purposes, mainly because of technical limitations, the most prominent of which is the effect of soft-tissue attenuation on apparent tracer distribution. Providers have attempted to compensate for this by a number of indirect approaches. Recently, validated hardware and software solutions for directly correcting image data for soft-tissue attenuation have become widely available commercially. Optimal application requires an understanding of the technical details that differ somewhat from system to system, the quality control prerequisites, knowledge of the importance of the transmission map quality, and how dedicated SPECT and SPECT-computed tomography systems present different challenges. In addition, the clinical literature is expanding rapidly, including studies on diagnostic accuracy, image appearances, quantitative analysis, appropriate patients for attenuation correction, clinical utility, incremental value in relation to ECG-gating, and risk stratification.

Quantitative Tc-99m sestamibi attenuation-corrected SPECT: development and multicenter trial validation of myocardial perfusion stress gender-independent normal database in an obese population.

BACKGROUND: A gender-independent stress normal database and criteria for abnormality for attenuation-corrected rest-stress technetium 99m sestamibi same-day myocardial perfusion imaging were developed by evaluation of 112 patients, validated against an obese population of 95 patients from four different clinical sites, and compared with conventional gender-matched database quantification of non-attenuation-corrected studies. METHODS AND RESULTS: These 95 validation patients (63 men) were used for prospective quantitative evaluation (mean weight, 213 +/- 57 lb; mean body mass index, 32 +/- 9 kg/m(2)). This group included 21 patients (12 men) with a lower than 5% likelihood of coronary artery disease (mean weight, 226 +/- 72 lb; mean body mass index, 34 +/- 13 kg/m(2)) and 74 who underwent cardiac catheterization within 2 months (35 with normal coronaries or coronary lesions <70%). These studies were processed twice, once by use of conventional reconstruction and gender-specific database quantification and a second time by use of attenuation correction and a single gender-independent attenuation-corrected normal database. The attenuation-corrected normal database and criteria for abnormality were developed by evaluation of 48 and 78 patients, respectively. No statistically significant differences were found when comparing attenuation-corrected perfusion distributions of normal men and women, whereas significant differences were found in the same uncorrected studies. Compared with quantitative analysis of the uncorrected studies, quantitative analysis of the attenuation-corrected studies by use of a gender-independent normal database demonstrated a significant improvement in normalcy rate (90% vs 52%, P =.006) and specificity (57% vs 29%, P =.015) in this obese population at no significant loss in sensitivity (90% vs 97%, P = not significant). CONCLUSION: Attenuation-corrected studies can be quantified with a single gender-independent normal database and a single criterion for abnormality without loss of sensitivity and with significantly better specificity and normalcy rate.

Clinical value of attenuation correction in stress-only Tc-99m sestamibi SPECT imaging.

BACKGROUND: Attenuation artifact remains a substantial limitation to confident interpretation of images and reduces laboratory efficiency by requiring comparison of stress and rest image sets. Attenuation-corrected stress-only imaging has the potential to ameliorate these limitations. METHODS AND RESULTS: Ten experienced nuclear cardiologists independently interpreted 90 stress-only electrocardiography (ECG)-gated technetium 99m sestamibi images in a sequential fashion: myocardial perfusion imaging (MPI) alone, MPI plus ECG-gated data, and attenuation-corrected MPI with ECG-gated data. Images were interpreted for diagnostic certainty (normal, probably normal, equivocal, probably abnormal, abnormal, and perceived need for rest imaging). With stress MPI data alone, only 37% of studies were interpreted as definitely normal or abnormal, with a very high perceived need for rest imaging (77%). The addition of gated data did not alter the interpretations. However, attenuation-corrected data significantly increased the number of studies characterized as definitely normal or abnormal (84%, P <.005) and significantly reduced the perceived need for rest imaging (43%, P <.005). These results were confirmed by use of a nonsequential consensus interpretation of three readers. CONCLUSION: Attenuation correction applied to studies with stress-only Tc-99m ECG-gated single photon emission computed tomography images significantly increases the ability to interpret studies as definitely normal or abnormal and reduces the need for rest imaging. These findings may improve laboratory efficiency and diagnostic accuracy.