Chonnam Med J.  2017 May;53(2):95-102. 10.4068/cmj.2017.53.2.95.

Structure-Inherent Targeting of Near-Infrared Fluorophores for Image-Guided Surgery

• Jo D
• Hyun H

• KMID: 2379281
• DOI: http://doi.org/10.4068/cmj.2017.53.2.95

Abstract

Although various clinical imaging modalities have been developed to visualize internal body structures and detect abnormal tissues prior to surgical procedures, most medical imaging modalities do not provide disease-specific images in real-time. Optical imaging can provide the surgeon with real-time visualization of the surgical field for intraoperative image-guided surgery. Imaging in the near-infrared (NIR) window (650-900 nm), also known as the "therapeutic window" has high potential by offering low absorbance and scattering in tissues resulting in minimized background autofluorescence. Clinically, optical fluorescence imaging with the targeted contrast agents provides opportunities for significant advances in intraoperative image-guided surgery. There are only two clinically available NIR fluorophores, indocyanine green (ICG) and methylene blue (MB), that support the image-guided surgery. However, neither of them perform in vivo by providing optimum specificity and stability for targeted image guidance. Therefore, it is of paramount importance to develop targeted NIR fluorophores for unmet clinical needs. Using the right combination of an NIR fluorescence imaging system and a targeted fluorophore, the desired target tissues can be imaged to provide real-time fluorescence guidance without changing the field-of-view during surgery. Thus, in a clinical discipline, the development of NIR fluorophores for "˜structure-inherent targeting' is an unmet need for early phase diagnostics with accurate targeting.

Keyword

Fluorescent Dyes; Fluorescence; Optical Imaging; Surgery

MeSH Terms

Contrast Media
Diagnostic Imaging
Fluorescence
Fluorescent Dyes
Indocyanine Green
Methylene Blue
Optical Imaging
Sensitivity and Specificity
Surgery, Computer-Assisted*
Contrast Media
Fluorescent Dyes
Indocyanine Green
Methylene Blue

Figure

• 

  FIG. 1 Schematic of dual-channel intraoperative NIR fluorescence imaging. A targeted NIR fluorophore is administered intravenously, topically, or intraparenchymally. During surgery, the fluorophore is visualized using a NIR fluorescence imaging system above the surgical field for open surgery or encased within a fiberscope for minimally-invasive and robotic surgery. All systems must have adequate NIR excitation lights (i.e., NIR1 for 700 nm fluorescence and NIR2 for 800 nm fluorescence), collection optics and filtration, and a camera sensitive to NIR fluorescence emission lights. An optimal imaging system includes simultaneous visible (i.e., white) light illumination of the surgical field, which can be merged with NIR fluorescence images. The surgeon display can be one of several forms factors including a standard computer monitor, goggles, or a wall projector (monitor form factor shown). Current imaging systems operate at a sufficient working distance that enables the surgeon to operate and illuminates a sizable surgical field. The monitor image is reproduced with permission from ref 43 (Copyright 2013 Wiley-VCH).

• 

  FIG. 2 Examples of structure-inherent targeting of the engineered NIR fluorophores. Reproduced with permission from ref 40 (for Thyroid and Parathyroid images, Copyright 2015 Nature Publishing Group), ref 48 (for Lymph Node image, Copyright 2014 Ivyspring International Publisher), ref 51 (for Nerve image, Copyright 2014 Ivyspring International Publisher), ref 56 (for Bone image, Copyright 2014 Wiley-VCH), ref 57 (for Catilage image, Copyright 2015 Wiley-VCH), ref 58 (for Adrenal image, Copyright 2015 ACS Publications), ref 59 (for Pituitary and Salivery images, Copyright 2016 ACS Publications), and ref 62 (for Pancreas image, Copyright 2015 Ivyspring International Publisher).

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