title: Calf flow reserve with H(2)(15)O PET as a quantifiable index of lower extremity flow.
abstract: Objective measures of recruitable blood flow are of importance in angiogenesis trials. We validated a new PET-derived flow reserve (FR) measurement in healthy subjects and subjects with peripheral artery disease (PAD).
  
  
  METHODS
  Five healthy volunteers and 5 subjects with PAD underwent cannulation of the femoral artery and vein. Basal and maximal flow (100 micro g/kg/min of adenosine infused intraarterially) in the lower extremity was determined using thermodilution (TD) techniques. Subjects then underwent plethysmography (PL) followed by PET measurements of blood flow at the calf level. For the PET studies, a transmission scan followed by injection of 1.85 GBq (50 mCi) H(2)(15)O and dynamic scanning for 5 min were acquired in five 1-min frames. Regions of interest were drawn on successive PET image slices, and radioactivity was quantified from the first-minute scan after injection. FR for each of the 3 modalities was expressed as the ratio of adenosine to basal flow.
  
  
  RESULTS
  PET-derived FR correlated strongly with TD (r = 0.82; P = 0.004) but not with PL (r = 0.17; P = 0.85). The mean average difference in FR between healthy volunteers and PAD subjects was 13.0 with PET and 4.5 with TD. The intra- and intersubject variability for PET expressed as the coefficient of variation was 10.5% and 29.0% for healthy subjects and 7.0% and 52.9% in PAD, respectively.
  
  
  CONCLUSIONS
  As expected, FR was significantly lower in PAD subjects compared with healthy subjects as assessed with TD and PET but not with PL. PET-derived FR appears to be reproducible and generates sharper and higher indices of recruitable flow in healthy subjects and PAD. These findings have implications for the use of PET-derived FR as a sensitive index of recruitable flow in angiogenesis trials.
authors.affiliation: Section of Vascular Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schmidt
authors.forename: Anjan
authors.initials: A
authors.lastname: Chakrabarti
authors.forename: Qurratul
authors.initials: Q
authors.lastname: Shamim-Uzzaman
authors.forename: Niko
authors.initials: N
authors.lastname: Kaciroti
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D000241:Adenosine; D000328:Adult; D001158:Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology; D001783:Blood Flow Velocity; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D006801:Humans; D006859:Hydrogen / Q000493:pharmacokinetics; D035002:Lower Extremity / Q000098:blood supply / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000000981:diagnostic imaging*; D018919:Neovascularization, Physiologic; D010104:Oxygen Radioisotopes / Q000493:pharmacokinetics; D016491:Peripheral Vascular Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology; D010991:Plethysmography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012039:Regional Blood Flow; D013815:Thermodilution; D013848:Thigh / Q000098:blood supply / Q000000981:diagnostic imaging; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: D010104:Oxygen Radioisotopes; D019275:Radiopharmaceuticals; D006859:Hydrogen; D000241:Adenosine