title: Noninvasive determination of spatially resolved and time-resolved tissue perfusion in humans during nitric oxide inhibition and inhalation by use of a visible-reflectance hyperspectral imaging technique.
abstract: BACKGROUND
  Vascular disease is commonly associated with reduced local synthesis of nitric oxide (NO) and impaired tissue perfusion. We introduce a novel noninvasive, visible-reflectance, hyperspectral imaging technique for quantifying the percentage of hemoglobin existing as oxyhemoglobin (HbO(2)) as an index of skin tissue perfusion.
  
  
  RESULTS
  To simulate vascular endothelial dysfunction, N(G)-monomethyl-L-arginine (L-NMMA) was infused into the brachial arteries of 9 healthy subjects for 5 minutes to inhibit forearm NO synthesis, first with the subject breathing room air and subsequently during NO inhalation at 80 ppm for 1 hour. Blood flow was measured by venous occlusion plethysmography, and the percentage of HbO(2) perfusing skin tissue was imaged noninvasively with a visible-reflectance hyperspectral technique. L-NMMA reduced blood flow by 31.7+/-4.9% and percentage of HbO(2) by 6.5+/-0.1 (P=0.002 and P<0.001 versus baseline, respectively). With subjects inhaling NO, blood flow fell during L-NMMA infusion by only 10.9+/-7.3%, and the percentage of HbO(2) decreased by 3.6+/-0.1 (P=0.007 and P<0.001, respectively, versus room air L-NMMA responses).
  
  
  CONCLUSIONS
  Visible-reflectance hyperspectral imaging demonstrates (1) a significant decline in the percentage of HbO(2) in skin tissue when blood flow is reduced after inhibition of forearm NO synthesis and (2) restoration of HbO(2) toward basal values with improved blood flow during inhalation of NO. This imaging method may provide an effective approach for time-resolved noninvasive monitoring of skin hemoglobin oxygen saturation and assessment of responses to therapeutic interventions in patients with vascular disease.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892-0510, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Zuzak
authors.forename: M D
authors.initials: MD
authors.lastname: Schaeberle
authors.forename: M T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: R O
authors.initials: RO
authors.lastname: Cannon
authors.forename: I W
authors.initials: IW
authors.lastname: Levin
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006225:Hand; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006454:Hemoglobins; D010108:Oxyhemoglobins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C100003:deoxyhemoglobin; D019001:Nitric Oxide Synthase; D010100:Oxygen