title: Optimal Adenosine Stress for Maximum Stress Perfusion, Coronary Flow Reserve, and Pixel Distribution of Coronary Flow Capacity by Kolmogorov-Smirnov Analysis.
abstract: Different adenosine stress imaging protocols have not been systemically validated for absolute myocardial perfusion and coronary flow reserve (CFR) by positron emission tomography, where submaximal stress precludes assessing physiological severity of coronary artery disease.
  
  
  
  In 127 volunteers, serial rest-stress positron emission tomography scans using rubidium-82 with various adenosine infusion protocols identified (1) the protocol with maximum stress perfusion and CFR, (2) test-retest precision in same subject, (3) stress perfusion and CFR after adenosine compared with dipyridamole, (4) heterogeneity of coronary flow capacity combining stress perfusion and CFR, and (5) potential relevance for patients with risk factors or coronary artery disease. The adenosine 6-minute infusion with rubidium-82 injection at 3 minutes caused CFR that was significantly 15.7% higher than the 4-minute adenosine infusion with rubidium-82 injection at 2 minutes and significantly more homogeneous by Kolmogorov-Smirnov analysis for histograms of 1344 pixel range of perfusion in paired positron emission tomographies. In a coronary artery disease cohort separate from volunteers of this study, compared with the 3/6-minute protocol, the 2/4-minute adenosine protocol would potentially have changed 332 of 1732 (19%) positron emission tomographies at low-risk physiological severity CFR ≥2.3 to CFR <2.0, thereby implying high-risk quantitative severity potentially appropriate for interventions but because of suboptimal stress of the 2/4 protocol in some patients.
  
  
  
  The 6-minute adenosine infusion with rubidium-82 activation at 3 minutes produced CFR that averaged 15.7% higher than that in the 2/4-minute protocol, thereby potentially providing essential information for personalized management in some patients.
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.).
authors.forename: Danai
authors.initials: D
authors.lastname: Kitkungvan
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.).
authors.forename: Dejian
authors.initials: D
authors.lastname: Lai
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.).
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhu
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.).
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Roby
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.).
authors.forename: Nils P
authors.initials: NP
authors.lastname: Johnson
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.).
authors.forename: Derek D
authors.initials: DD
authors.lastname: Steptoe
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.).
authors.forename: Monica B
authors.initials: MB
authors.lastname: Patel
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.).
authors.forename: Richard
authors.initials: R
authors.lastname: Kirkeeide
authors.affiliation: From the Weatherhead PET Center For Preventing and Reversing Atherosclerosis (A.E.R., D.D.S., K.L.G.), Division of Cardiology, Department of Medicine (D.K., N.P.J., M.B.P., R.K.), McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston; and Department of Biostatistics, School of Public Health, The University of Texas Health Science Center at Houston (D.L., H.Z.). k.lance.gould@uth.tmc.edu.
authors.forename: K Lance
authors.initials: KL
authors.lastname: Gould
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004176:Dipyridamole / Q000008:administration & dosage; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D015203:Reproducibility of Results; D012414:Rubidium Radioisotopes / Q000008:administration & dosage; D018709:Statistics, Nonparametric; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D019275:Radiopharmaceuticals; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents; D004176:Dipyridamole; D000241:Adenosine
keywords: Kolmogorov–Smirnov statistic; adenosine; adenosine stress; cardiac positron emission tomography; coronary flow; coronary flow reserve; quantitative myocardial perfusion