Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography

doi:10.1016/0002-8703(87)90702-2

American Heart Journal

Volume 113, Issue 3, March 1987, Pages 645-654

https://doi.org/10.1016/0002-8703(87)90702-2 Get rights and content

Abstract

In order to evaluate the detectability of coronary artery disease (CAD) with positron-emission computed tomography (PET), we performed ¹³N-ammonia myocardial PET scanning at rest and with exercise loading in 20 normal subjects and 40 patients with CAD, by means of a high-resolution, multi-slice, whole-body PET scanner. Myocardial PET scanning was performed 3 minutes after injection of ¹³N-ammonia at rest and during exercise. The circumferential profile analysis of resting PET images revealed regional hyporerfusion in 96% of CAD patients with previous myocardial infarction and in 29% of those without infarction. Exercise PET studies showed high sensitivity (93%) in detecting CAD without myocardial infarction, whereas no abnormal hypoperfusion was detected in normal subjects. Segmental analysis of regional myocardial perfusion with exercise stress identified 67 of 75 stenosed vessels (89%). We conclude that ¹³N-ammonia myocardial PET with exercise loading provides high-quality tomographic images of regional myocardial perfusion and is a valuable technique for detecting CAD.

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The Role of Noninvasive Imaging in Coronary Artery Disease Detection, Prognosis, and Clinical Decision Making
2013, Canadian Journal of Cardiology
Citation Excerpt :
A recent meta-analysis comparing diagnostic accuracy of SPECT and PET included only those studies using both attenuation correction and gating and found a sensitivity of 85% and a specificity of 85%.13 PET MPI has been demonstrated to possess superior accuracy than that of SPECT for the detection of CAD (Table 1).11,18,19-22 In a PET meta-analysis (1442 patients), the mean sensitivity and specificity of PET for CAD detection was 92% and 85% respectively (Table 1).23
A vast array of noninvasive imaging modalities is available for the evaluation of the presence and severity of coronary artery disease (CAD). Choosing the right test can be challenging but is critical for proper patient diagnosis and management. Presently available imaging tests for CAD include: (1) nuclear myocardial perfusion imaging procedures (single-photon emission tomography) and positron emission tomography, (2) stress echocardiography, (3) computed tomography coronary angiography, and (4) cardiac magnetic resonance imaging. Exercise treadmill testing electrocardiography is another alternative that we will discuss briefly. Selection of the most appropriate imaging modality requires knowledge of the clinical question being addressed, patient characteristics (pretest probability and prevalence of disease), the strengths, limitations, risks, costs, and availability of each procedure. To assist with test selection, we review the relevant literature in detail to consider the relative merits of cardiac imaging modalities for: (1) detection of CAD, (2) risk stratification and prognostication, and (3) guiding clinical decision making.
Un large éventail de modalités d’imagerie non effractive est disponible pour l’évaluation de la présence et de la gravité de la maladie coronarienne (MC). Choisir le bon examen peut être difficile, mais s’avère crucial pour le diagnostic et la prise en charge appropriés du patient. Les examens d’imagerie actuellement disponibles pour la MC incluent : 1) les interventions de scintigraphie myocardique de perfusion (tomographie par émission de photon unique) et la tomographie par émission de positons; 2) l’échocardiographie de stress; 3) la coronarographie par tomodensitométrie; 4) l’imagerie par résonance magnétique cardiaque. L’électrocardiographie à l’effort est une autre solution dont nous discuterons brièvement. Le choix de la modalité d’imagerie la plus appropriée exige de connaître les questions cliniques traitées, les caractéristiques du patient (la probabilité avant l’examen et la prévalence de la maladie), les forces, les limites, les risques, les coûts et la disponibilité de chaque intervention. Pour aider à choisir l’examen, nous examinons en détail la littérature pertinente pour explorer les avantages relatifs des modalités d’imagerie cardiaque dans : 1) la détection de la MC; 2) la stratification du risque et la pronostication; 3) l’orientation de la prise de décision clinique.
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Diagnosis and prognosis in cardiac disease using cardiac PET perfusion imaging
2010, Clinical Nuclear Cardiology
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2009, Cardiology Clinics
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In practice, the use of PET MPI as a first-line functional evaluation is generally reserved for those who may be prone to attenuation artifact (eg, obesity) or for those patients for whom the most definitive functional evaluation is required, as may be the case for a patient who has a moderate lesion on angiogram to determine hemodynamic significance before considering revascularization. A recent review reported that the mean sensitivity and specificity of PET MPI for diagnosis of CAD were 89% and 90% with ranges from 83% to 100% and 73% to 100%, respectively (Table 2).9,34–49 Six studies comparing CAD diagnostic accuracy have demonstrated superiority of 82Rb or 13NH3 PET MPI compared with 201Tl SPECT imaging.9,34,35,41,50,51
In the last two decades, the field of nuclear cardiology has experienced significant progress. The introduction of positron emission tomography (PET) imaging represented a major breakthrough that has significantly contributed to a better understanding of physiology and pathophysiology of several heart diseases. Currently, PET imaging is recognized as a well-established method to assess cardiac perfusion, function, metabolism, and viability. This article summarizes the main clinical applications of state-of-the art cardiac PET technology.
Diagnostic Performance of Positron Emission Tomography in the Detection of Coronary Artery Disease. A Meta-analysis
2008, Academic Radiology
Citation Excerpt :
Nineteen studies were included, with 6 being excluded because (a) they had overlapping data or (b) it was not possible to calculate absolute figures from the presented data. Study and population characteristics of the included studies are summarized in Table 1 (4–22). Data on diagnostic accuracy were available for the 19 studies with a total of 1442 patients.
Although myocardial perfusion positron emission tomography (PET), using either cyclotron-produced ammonia or generator-produced rubidium 82, has reported excellent diagnostic capabilities in the detection of coronary artery disease (CAD) in individual studies, the technique is not widely used in practice. This may be driven by cost and availability or by unawareness of performance. The purpose of our study was to conduct an evidence-based evaluation of PET in the diagnosis of CAD.
We examined studies from January 1977 to July 2007 using MEDLINE and EMBASE. A study was included if it (1) used PET as a diagnostic test for CAD and (2) used catheter x-ray angiography as the reference standard (≥50% diameter stenosis). Analysis was performed on a subject and coronary territory level.
Nineteen studies (1442 patients) met the inclusion criteria. On a patient level, PET demonstrated a sensitivity of 0.92 (95% confidence interval [CI]: 0.90–0.94) and specificity of 0.85 (CI: 0.79–0.90), with a positive likelihood ratio (LR+) of 6.2 (CI: 3.3–11.8) and negative likelihood ratio (LR−) of 0.11 (CI: 0.08–0.14). On a coronary territory level (n = 1130), PET showed a sensitivity of 0.81 (CI: 0.77–0.84) and specificity of 0.87 (CI: 0.84–0.90), with an LR+ of 5.9 (CI: 4.5-7.9) and an LR− of 0.19 (CI: 0.09–0.38).
PET demonstrates excellent diagnostic properties in the diagnosis of CAD, especially at the patient level. The capabilities appear superior to those reported in meta-analyses for perfusion imaging with Tl-201 and sestamibi, or anatomical imaging with coronary MDCT angiography or MRA. Given that previous studies have found PET to be cost-effective and the current findings of excellent sensitivity and specificity, the modality should be more widely considered as an initial test in the diagnosis of CAD.
Metabolism of [<sup>13</sup>N]ammonia in rat lung
2005, Neurochemistry International
Citation Excerpt :
13N also has been used, for example, to study nitrogen fluxes in microorganisms (e.g., Encarnación et al., 1998) and the metabolic fate of labeled chemotherapeutic drugs (e.g., Freed et al., 1982; Ginos et al., 1987). Measurement in vivo, by positron emission tomography (PET), of tracer concentrations following [13N]ammonia injection, has been used as an index of blood flow in the normal and diseased human heart (e.g., Yonekura et al., 1985; Krivokapich et al., 1987, 1989; Nienaber et al., 1991, 1993; Czernin et al., 1993; Choi et al., 1999; Schöder et al., 2000; Kudo et al., 2002; Gropler and Soto, 2004) and in the kidney (Chen et al., 1993). Among the advantages of radioactive 13N over the non-radioactive nitrogen tracer 15N are that the label content of whole organs can be measured in vivo, that label quantitation in relatively large in vitro specimens requires little, if any, specimen preparation, and that tracing the pathways of endogenous substances incurs far less interference from natural background.
Bolus injection of [¹³N]ammonia into the femoral vein of pentobarbital-anesthetized rats was followed by rapid clearance from the blood and first-pass extraction of nearly 30% by the lungs. Of the label present in the lungs at 6 s after injection (about 27% of the dose), more than 20% was in metabolized form. Of the label present in the lungs at 2 min after injection (about 10% of the dose), 18–25% was in ammonia, about 75% was in glutamine (amide) and less than 1% was in glutamate and aspartate. Thus, despite the presence of significant amounts of glutamate dehydrogenase, the overwhelming route for metabolism of ammonia entering the rat lung in vivo was the glutamine synthetase reaction. Lung tissue that was removed 6 s after intravenous injection of [¹³N]ammonia and incubated in Krebs–Ringer glucose medium at 37 °C for 20 min, showed a significant increase (more than one-third), compared to unincubated lung tissue in the quantity of label in glutamine. Between 6 s and 2 min after injection, during which time the total ¹³N content of the lungs decreased by more than 60%, the maintenance of a quasi-steady state in the concentration of labeled glutamine suggested a short-term balance between formation from extracted ammonia and loss of glutamine into the circulation. Our data support the concept that the lungs are a source of circulating glutamine in the rat. Despite the large fractional extraction of blood-borne [¹³N]ammonia by the lungs, only minute amounts of tracer (0.2–0.6 ppm of the injected dose) were detected in the expired air within the first 5 min after administration of [¹³N]ammonia to anesthetized rats, so that pulmonary excretion was not a significant pathway of ammonia elimination. The present findings emphasize the importance of the lungs in the maintenance of whole-body nitrogen homeostasis and suggest the use of [¹³N]ammonia and ¹³N-labeled amino acids as non-invasive probes in the study of normal and diseased lung metabolism.

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^☆: Supported in part by Japanese Ministry of Education grant 60010039.

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Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography☆

Abstract

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Determination of radionuclide concentrations with position CT scanning (PETT)

J Nucl Med

In vivo quantitation of regional myocardial blood flow by positronemission computed tomography

Circulation

Accurate in vivo measurement of regional myocardial blood flow by positron emission tomography (PET)

Circulation

Quantitation in positron emission computed tomography. 1. Effect of object size

J Comput Assist Tomogr

Performance characteristics of Positologica III, a whole-body positron emission tomograph

J Comput Assist Tomogr

Detection of coronary artery disease with ¹³N-ammonia and high-resolution positron-emission computed tomography☆