title: Noninvasive in vivo monitoring of methemoglobin formation and reduction with broadband diffuse optical spectroscopy.
abstract: We present noninvasive, quantitative in vivo measurements of methemoglobin formation and reduction in a rabbit model using broadband diffuse optical spectroscopy (DOS). Broadband DOS combines multifrequency frequency-domain photon migration (FDPM) with time-independent near infrared (NIR) spectroscopy to quantitatively measure bulk tissue absorption and scattering spectra between 600 nm and 1,000 nm. Tissue concentrations (denoted by brackets) of methemoglobin ([MetHb]), deoxyhemoglobin ([Hb-R]), and oxyhemoglobin ([HbO2]) were determined from absorption spectra acquired in "real time" during nitrite infusions in nine pathogen-free New Zealand White rabbits. As little as 30 nM [MetHb] changes were detected for levels of [MetHb] that ranged from 0.80 to 5.72 microM, representing 2.2 to 14.9% of the total hemoglobin content (%MetHb). These values agreed well with on-site ex vivo cooximetry data (r2= 0.902, P < 0.0001, n = 4). The reduction of MetHb to functional hemoglobins was also carried out with intravenous injections of methylene blue (MB). As little as 10 nM changes in [MB] were detectable at levels of up to 150 nM in tissue. Our results demonstrate, for the first time, the ability of broadband DOS to noninvasively quantify real-time changes in [MetHb] and four additional chromophore concentrations ([Hb-R], [HbO2], [H2O], and [MB]) despite significant overlapping spectral features. These techniques are expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and preclinical animal models.
authors.affiliation: Laser Microbeam and Medical Program, Beckman Laser Institute, 1002 Health Sciences Rd. East, University of California, Irvine, CA 92612-1475, USA.
authors.forename: Jangwoen
authors.initials: J
authors.lastname: Lee
authors.forename: Naglaa
authors.initials: N
authors.lastname: El-Abaddi
authors.forename: Andrew
authors.initials: A
authors.lastname: Duke
authors.forename: Albert E
authors.initials: AE
authors.lastname: Cerussi
authors.forename: Matthew
authors.initials: M
authors.lastname: Brenner
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Tromberg
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000378:metabolism; D007700:Kinetics; D008706:Methemoglobin / Q000378:metabolism*; D008708:Methemoglobinemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008751:Methylene Blue / Q000008:administration & dosage / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000378:metabolism; D017785:Photons; D011817:Rabbits; D012542:Scattering, Radiation; D012977:Sodium Nitrite; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000379:methods*
chemical_list: D006454:Hemoglobins; D010108:Oxyhemoglobins; C100003:deoxyhemoglobin; D008706:Methemoglobin; D012977:Sodium Nitrite; D008751:Methylene Blue