title: Intraoperative fluorescence imaging of peripheral and central nerves through a myelin-selective contrast agent.
abstract: OBJECTIVE
  Patients suffer from complications as a result of unintentional nerve damage during surgery. We focus on improving intraoperative visualization of nerves through the use of a targeted fluorophore and optical imaging instrumentation.
  
  
  METHODS
  A myelin-targeting fluorophore, GE3111, was synthesized, characterized for its optical and myelin-binding properties using purified myelin basic protein, and evaluated in mice. Additionally, a compact instrument was adapted to visualize nerves.
  
  
  RESULTS
  GE3111 was synthesized using a versatile methodology. Its optical properties were sensitive to the local environment both in vitro and in vivo. Following intravenous injection, central and peripheral nerves were visualized, with the kinetics of nerve uptake modifiable depending on the formulation. Fluorescence polarization showed specific and strong binding to purified myelin basic protein. Nerves were visualized in vivo using a dedicated compact imaging device requiring less than 2.5 mW/cm(2) of illumination at 405 nm.
  
  
  CONCLUSIONS
  Fluorescence imaging of nerves through myelin showed a potential for use in image-guided surgery. Intraoperative nerve imaging is an example where contrast agent and instrument development come together as a result of clinical need.
authors.affiliation: GE Global Research, One Research Circle, Niskayuna, NY 12309, USA.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Cotero
authors.forename: Tiberiu
authors.initials: T
authors.lastname: Siclovan
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Randall L
authors.initials: RL
authors.lastname: Carter
authors.forename: Anshika
authors.initials: A
authors.lastname: Bajaj
authors.forename: Nicole E
authors.initials: NE
authors.lastname: LaPlante
authors.forename: Evgenia
authors.initials: E
authors.lastname: Kim
authors.forename: Daniel
authors.initials: D
authors.lastname: Gray
authors.forename: V Paul
authors.initials: VP
authors.lastname: Staudinger
authors.forename: Siavash
authors.initials: S
authors.lastname: Yazdanfar
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Tan Hehir
mesh_terms: D061605:Administration, Intravenous; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002417:Cattle; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D003952:Diagnostic Imaging / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D007432:Intraoperative Period; D008297:Male; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000473:pathology*; D055620:Optical Phenomena; D009928:Organ Specificity; D010525:Peripheral Nerves / Q000473:pathology*; D012997:Solvents / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D025321:Surgery, Computer-Assisted
chemical_list: C578619:1-methylsulfonyl-4-(2-(4-(2-(4-aminophenyl)ethenyl)-3-methoxyphenyl)ethenyl)benzene; D000814:Aniline Compounds; D003287:Contrast Media; D004676:Myelin Basic Protein; D012997:Solvents; D013449:Sulfonamides