Fabio Esteves

Cardiac Dedicated Ultrafast SPECT Cameras: New Designs and Clinical Implications

Myocardial perfusion imaging (MPI) using nuclear cardiology techniques has been widely applied in clinical practice because of its well-documented value in the diagnosis and prognosis of coronary artery disease. Industry has developed innovative designs for dedicated cardiac SPECT cameras that constrain the entire detector area to imaging just the heart. New software that recovers image resolution and limits image noise has also been implemented. These SPECT innovations are resulting in shortened study times or reduced radiation doses to patients, promoting easier scheduling, higher patient satisfaction, and, importantly, higher image quality. This article describes these cardiocentric SPECT software and hardware innovations, which provide a strong foundation for the continued success of myocardial perfusion SPECT.

CD34+ cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent

BACKGROUND the objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow-derived CD34(+) cells after ST elevation myocardial infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells. METHODS patients were randomized to bone marrow harvest (n = 16) or control (n = 15). At a median of 8.3 days after coronary stenting for STEMI, CD34(+) cells were infused via the IRA at 3 dose levels (5, 10, and 15 × 10(6)) in cohorts of 5 patients each. Baseline and follow-up imaging and ex vivo CD34(+) cell mobility were performed. RESULTS Cell harvest and infusion were safe. Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the ≥ 10 million cohorts compared with controls (-256 vs +14, P = .02). There was a trend toward improved ejection fraction at 6 months (+4.5%) in the ≥ 10 million cohorts compared with no change in the controls and 5 million cohort (+0.7%). Improved perfusion and infarct size reduction correlated with the quantity and mobility of the infused CD34(+) cells. CONCLUSIONS the effects of CD34(+) cell IRA infusion during the repair phase after STEMI are dose dependent and, at a threshold dose of 10 million CD34(+) cells, associated with a significant improvement in perfusion that may limit deterioration in cardiac function (IRA infusion of CD34(+) cells in patients with acute myocardial infarction [AMR-01] NCT00313339).

Minimizing artifacts resulting from respiratory and cardiac motion by optimization of the transmission scan in cardiac PET/CT

The introduction of positron emission/computed tomography (PET/CT) systems coupled with multidetector CT arrays has greatly increased the amount of clinical information in myocardial perfusion studies. The CT acquisition serves the dual role of providing high spatial anatomical detail and attenuation correction for PET. However, the differences between the interaction of respiratory and cardiac cycles in the CT and PET acquisitions presents a challenge when using the CT to determine PET attenuation correction. Three CT attenuation correction protocols were tested for their ability to produce accurate emission images: gated, a step mode acquisition covering the diastolic heart phase; normal, a high-pitch helical CT; and slow, a low-pitch, low-temporal-resolution helical CT. The amount of cardiac tissue in the emission image that overlaid lung tissue in the transmission image was used as the measure of mismatch between acquisitions. Phantom studies simulating misalignment of the heart between the transmission and emission sequences were used to correlate the amount of mismatch with the artificial defect changes in the emission image. Consecutive patients were studied prospectively with either paired gated (diastolic phase, 120 kVp, 280 mA, 2.6 s) and slow CT (0.562:1 pitch, 120 kVp, Auto-mA, 16 s) or paired normal (0.938:1 pitch, 120 kVp, Auto-mA, 4.8 s) and slow CT protocols, prior to a Rb-82 perfusion study. To determine the amount of mismatch, the transmission and emission images were converted to binary representations of attenuating tissue and cardiac tissue and overlaid using their native registration. The number of cardiac tissue pixels from the emission image present in the CT lung field yielded the magnitude of misalignment represented in terms of volume, of where a small volume indicates better registration. Acquiring a slow CT improved registration between the transmission and emission acquisitions compared to the gated and normal CT protocols. The volume of PET cardiac tissue in the CT lung field was significantly lower (p < 0.03) for the slow CT protocol in both the rest and stress emission studies. Phantom studies showed that an overlaying volume greater than 2.6 mL would produce significant artificial defects as determined by a quantitative software package that employs a normal database. The percentage of patient studies with overlaying volume greater than 2.6 mL was reduced from 71% with the normal CT protocol to 28% with the slow CT protocol. The remaining 28% exhibited artifacts consistent with heart drift and patient motion that could not be corrected by adjusting the CT acquisition protocol. The low pitch of the slow CT protocol provided the best match to the emission study and is recommended for attenuation correction in cardiac PET/CT studies. Further reduction in artifacts arising from cardiac drift is required and warrants an image registration solution.

Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database.

The use of myocardial perfusion 82Rb PET/CT studies continues to increase but its accuracy using database quantification methods for the diagnosis of coronary artery disease (CAD) has not been established. Methods: A sex-independent normal database and criteria for abnormality for rest–stress 82Rb PET/CT myocardial perfusion imaging were developed and validated by evaluation of 281 patients (136 females: mean age ± SD, 63.3 ± 13.3 y; 145 males: mean age ± SD, 63.9 ± 12.8 y) who underwent a rest–adenosine stress 82Rb PET/CT study. These patients were divided into 3 groups: (a) healthy group: 30 patients, with <5% likelihood of CAD (low likelihood [LLK]) based on sequential Bayesian analysis; these patients were used to generate the normal distribution; (b) pilot group: 174 patients; these patients were used to determine the optimal criteria for detecting and localizing the perfusion abnormality; and (c) validation group: 76 patients (23 with LLK of CAD and 53 who underwent coronary angiography; these patients were used for prospective validation. Results: Of the 53 patients who underwent coronary angiography, 8 had <50% stenosis and 45 patients had at least one stenosis ≥50% in one major artery. Fifteen patients had single-vessel disease, 17 had double-vessel disease, and 13 had triple-vessel disease. The prospective validation shows a normalcy rate of 78% (18/23) for global CAD. The analyses by individual arteries show a normalcy rate of 96% (22/23) for the left anterior descending coronary artery, 96% for the left circumflex coronary artery (22/23), and 100% for the right coronary artery (23/23). The overall sensitivity for detection of CAD (≥50% stenosis) was 93% (42/45). The overall specificity for detection of the absence of CAD (≤50% stenosis) was 75% (6/8). Also, the positive predictive value for global CAD was 95% (42/44), the negative predictive value was 67% (6/9), and the accuracy was 91% (48/53). Conclusion: The quantitative 82Rb PET/CT database created and validated in this study is highly accurate for the detection and localization of CAD. Physicians should consider using the quantitative output of these algorithms as decision support tools to aid with image interpretation.

99mTc-MAG3 Renography: Normal Values for MAG3 Clearance and Curve Parameters, Excretory Parameters, and Residual Urine Volume

OBJECTIVE Specific quantitative measurements have been recommended to assist in the interpretation of technetium-99m mercaptoacetyltriglycine (MAG3) renal studies. Our objective was to define the sex- and age-specific normal ranges for these recommended parameters. MATERIALS AND METHODS Data were obtained from a retrospective analysis of 106 subjects who were evaluated for kidney donation. The MAG3 clearance was calculated using a common camera-based method. The relative uptake, prevoid/postvoid and postvoid/maximum count ratios were determined using whole-kidney regions of interest (ROIs). Time to peak, time to half-peak, 20 min/maximum and 20 min/2-3 min count ratios were determined for cortical and whole-kidney ROIs. Residual urine volume was calculated on the basis of the pre- and postvoid bladder counts and voided urine volume. RESULTS The mean camera-based MAG3 clearance was 321 +/- 69 mL/min/1.73 m2, essentially the same as the mean plasma sample MAG3 clearance in comparable populations. The percentages of relative uptake in the right and left kidneys were 49% and 51% +/- 4%, respectively; no difference was seen between men and women. Cortical values were lower than the whole-kidney values (p < 0.001); the mean cortical 20 min/maximum count ratio was 0.19 (SD, 0.07 and 0.04 for right and left kidneys, respectively). The mean postvoid/maximum whole-kidney count ratio was < 0.1, and the mean postvoid residual bladder volume was < 30 mL. CONCLUSION Normal limits adjusted for age and sex have been established. Applying normal ranges to quantitative MAG3 parameters may assist in the interpretation of MAG3 scintigraphy and facilitate appropriate patient management.

Myocardial ischemia during mental stress: role of coronary artery disease burden and vasomotion.

Background Mental stress–induced myocardial ischemia (MSIMI) is associated with adverse prognosis in patients with coronary artery disease (CAD), yet the mechanisms underlying this phenomenon remain unclear. We hypothesized that compared with exercise/pharmacological stress–induced myocardial ischemia (PSIMI) that is secondary to the atherosclerotic burden of CAD, MSIMI is primarily due to vasomotor changes. Methods and Results Patients with angiographically documented CAD underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and following both mental and physical stress testing, performed on separate days. The severity and extent of CAD were quantified using the Gensini and Sullivan scores. Peripheral arterial tonometry (Itamar Inc) was used to assess the digital microvascular tone during mental stress as a ratio of pulse wave amplitude during speech compared with baseline. Measurements were made in a discovery sample (n=225) and verified in a replication sample (n=159). In the pooled (n=384) sample, CAD severity and extent scores were not significantly different between those with and without MSIMI, whereas they were greater in those with compared with those without PSIMI (P<0.04 for all). The peripheral arterial tonometry ratio was lower in those with compared with those without MSIMI (0.55±0.36 versus 0.76±0.52, P=0.009). In a multivariable analysis, the peripheral arterial tonometry ratio was the only independent predictor of MSIMI (P=0.009), whereas angiographic severity and extent of CAD independently predicted PSIMI. Conclusions The degree of digital microvascular constriction, and not the angiographic burden of CAD, is associated with MSIMI. Varying causes of MSIMI compared with PSIMI may require different therapeutic interventions that require further study.

Assessment of acute myocardial infarction: current status and recommendations from the North American society for cardiovascular imaging and the European society of cardiac radiology

There are a number of imaging tests that are used in the setting of acute myocardial infarction and acute coronary syndrome. Each has their strengths and limitations. Experts from the European Society of Cardiac Radiology and the North American Society for Cardiovascular Imaging together with other prominent imagers reviewed the literature. It is clear that there is a definite role for imaging in these patients. While comparative accuracy, convenience and cost have largely guided test decisions in the past, the introduction of newer tests is being held to a higher standard which compares patient outcomes. Multicenter randomized comparative effectiveness trials with outcome measures are required.

Absent coronary artery calcium excludes inducible myocardial ischemia on computed tomography/positron emission tomography.

OBJECTIVE We set out to determine whether a coronary artery calcium (CAC) score of zero on computed tomography (CT) would predict a normal myocardial perfusion positron emission tomography (PET) in a population mostly at intermediate pretest likelihood of coronary artery disease (CAD). METHODS We enrolled 206 outpatients (36% men, mean age 60 ± 13 years) referred for Rb-82 myocardial perfusion PET/CT for suspected CAD. CAC scoring was performed by the Agatston method. The PET images were scored on a 5-point scale using a 17-segment left ventricular model. A summed stress score ≥ 2 was considered abnormal. Multivariable logistic regression analysis was used to test the independent predictive value of a CAC score of zero to exclude inducible myocardial ischemia. RESULTS Ninety-nine of 206 patients (48%) had a CAC score of zero and of these only 1 had inducible ischemia on PET. This yielded a negative predictive value of 99% (95% CI 95%-100%). CAC score of zero was the strongest independent predictor of a normal myocardial perfusion PET (OR = 0.05; 95% CI = 0.006-0.38; p = 0.004). CONCLUSION In a population of predominately intermediate likelihood of CAD, a CAC score of zero excludes inducible ischemia on myocardial perfusion PET.

Sex Differences in Mental Stress‐Induced Myocardial Ischemia in Patients With Coronary Heart Disease

Background Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress‐induced myocardial ischemia (MSIMI). Methods and Results We studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent 99mTc‐sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more‐adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, P<0.001) and the incidence of MSIMI was 82.6% higher (interaction, P=0.004) in women than in men. Incidence of MSIMI in women ≤50 years was almost 4‐fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress. Conclusions Young women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group.

Adenosine stress rubidium-82 PET/computed tomography in patients with known and suspected coronary artery disease.

BackgroundIntegrated positron emission tomography/computed tomography (PET/CT) is increasingly being utilized for myocardial perfusion imaging (MPI). However, there is a potential for increased imaging artifact compared with standard PET due to the different temporal resolution of PET and CT. We reviewed the diagnostic accuracy of adenosine stress 82Rb myocardial perfusion PET/CT to detect obstructive coronary artery disease (CAD) on invasive angiography at our institution. Methods and resultsSeventy-five patients were included, 23 (13 men, mean age 55.8±11.8 years) with low likelihood of CAD and 52 (28 men, mean age 67.1±11.4 years) with intermediate to high pretest probability of disease. Coronary angiography was performed only in the latter 52 patients on average within 17 days of the MPI study. The test characteristics of PET/CT MPI were assessed using a threshold of ≥50 and ≥70% stenosis in one or more major coronary artery on invasive angiography. Dedicated software was used for registration, processing, and interpretation. Consensus interpretation of the tomographic PET slices using a 4-point scale (1=definitely normal, 2=probably normal, 3=probably abnormal, 4=definitely abnormal) was done by two readers blinded to clinical information. ResultsAll MPI studies in the 23 low likelihood patients were normal. In the remaining 52 patients using a stenosis severity ≥50%, global sensitivity and specificity, negative and positive predictive value for detection of CAD were 86, 100, 57, and 100%. Using a stenosis severity ≥70%, these values changed to 90, 83, 71, and 87%. ConclusionAdenosine stress 82Rb MPI using PET/CT with manual registration demonstrates diagnostic accuracy comparable with that of traditional PET MPI.