title: Estimating coronary blood flow using CT transluminal attenuation flow encoding: Formulation, preclinical validation, and clinical feasibility.
abstract: BACKGROUND
  We present the formulation and testing of a new CT angiography (CTA)-based method for noninvasive measurement of absolute coronary blood flow (CBF) termed transluminal attenuation flow encoding (TAFE). CTA provides assessment of coronary plaque but does not allow for detection of vessel specific ischemia. A simple and direct method to calculate absolute CBF from a standard CTA could isolate the functional consequence of disease and aid therapy decisions.
  
  
  METHODS
  We present the theoretical framework and initial testing of TAFE. Nine canine models of ischemic heart disease were prepared and underwent CT imaging and microsphere measurements of myocardial blood flow. Additionally, 39 acute chest pain patients with normal coronary arteries underwent coronary CTA. We applied TAFE to calculate absolute CBF in the coronary arteries using 4 vessel input parameters including transluminal attenuation gradient, cross-sectional area, length, and the contrast bolus duration derived from the arterial input function.
  
  
  RESULTS
  In animal studies, TAFE-derived CBF in the left anterior descending, left circumflex, and right coronary artery was 20.8 ± 10.4 mL/min, 27.0 ± 13.4 mL/min, and 6.0 ± 3.7 mL/min, respectively. TAFE-derived CBF divided by myocardial mass strongly correlated with microsphere myocardial blood flow (R(2) = 0.90, P < .001). In human studies, TAFE-derived CBF in the left anterior descending, left circumflex, and right coronary artery was 26.4 ± 10.7 mL/min, 20.1 ± 13.0 mL/min, and 43.2 ± 40.9 mL/min, respectively. CBF per unit mass was 0.93 ± 0.48 mL/g/min in patients. Interobserver variability was minimal with excellent correlation (R = 0.96, P < .0001) and agreement (mean difference, 4.2 mL/min).
  
  
  CONCLUSIONS
  TAFE allows for quantification of absolute CBF from a standard CTA acquisition and may provide functional significance of coronary disease without complex computational methods.
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., 1042 Ross Building, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Mechanical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: al@jhmi.edu.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Lardo
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., 1042 Ross Building, Baltimore, MD, USA.
authors.forename: Amir Ali
authors.initials: AA
authors.lastname: Rahsepar
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Seo
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Parastou
authors.initials: P
authors.lastname: Eslami
authors.affiliation: Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Korley
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., 1042 Ross Building, Baltimore, MD, USA.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kishi
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., 1042 Ross Building, Baltimore, MD, USA.
authors.forename: Thura
authors.initials: T
authors.lastname: Abd
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Mittal
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., 1042 Ross Building, Baltimore, MD, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: George
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D005240:Feasibility Studies; D006801:Humans; D061330:Multidetector Computed Tomography; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D015588:Observer Variation; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011379:Prognosis; D012039:Regional Blood Flow; D015203:Reproducibility of Results
keywords: Computed tomography; Coronary atherosclerosis; Coronary blood flow; Fractional flow reserve; Myocardial ischemia; Transluminal attenuation gradients