Nerve-highlighting fluorescent contrast agents for image-guided surgery

Summer Gibbs, Khaled A. Nasr, Kenneth M. Fish, Onkar Khullar, Yoshitomo Ashitate, Tiberiu M. Siclovan, Bruce F. Johnson, Nicole E. Barnhardt, Cristina A. Tan Hehir, John V. Frangioni

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Nerve damage is the major morbidity of many surgeries, resulting in chronic pain, loss of function, or both. The sparing of nerves during surgical procedures is a vexing problem because surrounding tissue often obscures them. To date, systemically administered nerve-highlighting contrast agents that can be used for nerve-sparing image-guided surgery have not been reported. In the current study, physicochemical and optical properties of 4,49-[(2-methoxy-1,4- phenylene)di-(1E)-2,1-ethenediyl]bis-benzenamine (BMB) and a newly synthesized, red-shifted derivative 4-[(1E)-2-[4-[(1E)-2-[4-aminophenyl]ethenyl]-3- methoxyphenyl]ethenyl]-benzonitrile (GE3082) were characterized in vitro and in vivo. Both agents crossed the blood-nerve barrier and blood-brain barrier and rendered myelinated nerves fluorescent after a single systemic injection. Although both BMB and GE3082 also exhibited significant uptake in white adipose tissue, GE3082 underwent a hypsochromic shift in adipose tissue that provided a means to eliminate the unwanted signal using hyperspectral deconvolution. Dose and kinetic studies were performed in mice to determine the optimal dose and drugimaging interval. The results were confirmed in rat and pig, with the latter used to demonstrate, for the first time, simultaneous fluorescence imaging of blood vessels and nerves during surgery using the FLARE (Fluorescence-Assisted Resection and Exploration) imaging system. These results lay the foundation for the development of ideal nerve-highlighting fluorophores for image-guided surgery.

Original languageEnglish (US)
Pages (from-to)91-101
Number of pages11
JournalMolecular Imaging
Volume10
Issue number2
DOIs
StatePublished - Mar 2011
Externally publishedYes

Fingerprint

Computer-Assisted Surgery
nerves
Fluorescent Dyes
surgery
Surgery
Contrast Media
Blood-Nerve Barrier
Tissue
White Adipose Tissue
Fluorescence
Optical Imaging
adipose tissues
Blood-Brain Barrier
Chronic Pain
Blood Vessels
Fluorophores
Adipose Tissue
Blood vessels
Deconvolution
Swine

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Condensed Matter Physics

Cite this

Gibbs, S., Nasr, K. A., Fish, K. M., Khullar, O., Ashitate, Y., Siclovan, T. M., ... Frangioni, J. V. (2011). Nerve-highlighting fluorescent contrast agents for image-guided surgery. Molecular Imaging, 10(2), 91-101. https://doi.org/10.2310/7290.2010.00026

Nerve-highlighting fluorescent contrast agents for image-guided surgery. / Gibbs, Summer; Nasr, Khaled A.; Fish, Kenneth M.; Khullar, Onkar; Ashitate, Yoshitomo; Siclovan, Tiberiu M.; Johnson, Bruce F.; Barnhardt, Nicole E.; Tan Hehir, Cristina A.; Frangioni, John V.

In: Molecular Imaging, Vol. 10, No. 2, 03.2011, p. 91-101.

Research output: Contribution to journalArticle

Gibbs, S, Nasr, KA, Fish, KM, Khullar, O, Ashitate, Y, Siclovan, TM, Johnson, BF, Barnhardt, NE, Tan Hehir, CA & Frangioni, JV 2011, 'Nerve-highlighting fluorescent contrast agents for image-guided surgery', Molecular Imaging, vol. 10, no. 2, pp. 91-101. https://doi.org/10.2310/7290.2010.00026
Gibbs, Summer ; Nasr, Khaled A. ; Fish, Kenneth M. ; Khullar, Onkar ; Ashitate, Yoshitomo ; Siclovan, Tiberiu M. ; Johnson, Bruce F. ; Barnhardt, Nicole E. ; Tan Hehir, Cristina A. ; Frangioni, John V. / Nerve-highlighting fluorescent contrast agents for image-guided surgery. In: Molecular Imaging. 2011 ; Vol. 10, No. 2. pp. 91-101.
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