Application of Fluorescein Fluorescence in Vascular Neurosurgery

Abstract

Background: Fluorescein sodium (FNa) is a fluorescent drug with a long history of use for assessing retinal blood flow in ophthalmology; however, its application in vascular neurosurgery is only now gaining popularity. This review summarizes the current knowledge about using FNa videoangiography in vascular neurosurgery. Methods: We performed a literature review on the usage of FNa for fluorescent videoangiography procedures in neurosurgery. We analyzed methods of injection, dosages of FNa, visualizing platforms, and interpretation of FNa videoangiography. We also reviewed practical applications of FNa videoangiography during various vascular neurosurgeries. Results: FNa videoangiography can be performed with intraarterial (intracarotid) or intravenous dye injections. Both methods provide excellent resolution with enhanced fluorescence that shows intravascular blood flow on top of visible surrounding anatomy, and both allow simultaneous purposeful microsurgical manipulations. Although it is invasive, an intracarotid FNa injection results in faster contrast appearance and higher-intensity fluorescence and requires a lower dose per injection (reported range, 1-50 mg) compared with peripheral intravenous FNa injection (reported range, 75-2,000 mg or 1-1.5 mg/kg body weight). Four optical excitation/detection tools for FNa videoangiography have been successfully used: conventional xenon-light operating microscope with a special filter set, pencil-type light-emitting diode probe with a filter set, laser-illumination operating microscope, and an endoscope with a filter set. FNa videoangiography was reported to be feasible and useful in various clinical scenarios, such as examining the feeders and drainers in arteriovenous malformation surgery, checking the patency of a microvascular anastomosis, and assessing blood flow during aneurysm clipping. FNa videoangiography can be repeated during the same procedure and used along with indocyanine green (ICG) videoangiography. Conclusions: Compared with ICG videoangiography, FNa videoangiography has the advantages of enabling real-time inspection and better visualization at deep locations; however, thick vessel walls limit visualization of FNa in larger vessels. FNa videoangiography is a useful tool in multiple neurovascular scenarios and merits further studies to establish its clinical value.

Keywords: aneurysm; arteriovenous fistula; arteriovenous malformation; fluorescein angiography; fluorescein fluorescence; fluorescein sodium; vascular neurosurgery.

Figure 1

Graphic demonstrating the contrast and brightness changes during angiography with an (A) intravenous and (B) intraarterial FNa injection. The green color embedded in the bar above the graph represents the flow of the fluorescein. With an intravenous injection, the fluorescein is diluted and contrasts less as shown in the less steep and delayed graph, compared with an intraarterial injection during which the fluorescein is more concentrated and contrasts better as shown by the steep and acute graph. Max, maximum; Min, minimum. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Figure 2

Various platforms used for FNa videoangiography. (A–C) Operating microscope. (A) The operating microscope with Yellow 560 module (ZEISS KINEVO 900, Carl Zeiss AG, Oberkochen, Germany). (B) Intraoperative views of FNa videoangiography (left to right: arterial, capillary, and venous phases). (C) Patented filter combinations used in the operative microscope balances the intensities of narrow bands of excitation and emitted light to create a clear operating field view with yellow fluorescence of fluorescein. The excitation (bottom) and emission (top) profiles of fluorescein (peaks are 485 nm, blue; 514 nm, green, respectively) are shown on the background. The transmittance of filters at various wavelengths results in the uniform intensity of all bands, with a higher intensity of emitted yellow light. (D-H) Pencil-type probe with filter attached to the microscope objective lens. (D) The pencil-type probe with blue LED emission. (E) Sketch demonstrating the intraoperative usage of the probe. (F) The switch of the filter adapted to the operating microscope. (G) The intraoperative view using this device (left, fluorescence off; right, fluorescence on). (H) A diagram showing optical setup of the device. Blue LED light is concentrated around 465 nm, and a long-pass filter (black line) allows green emission light into the camera. (I-K) The laser microscope. (I) The illuminating device. (J) Images of the laser FNa videoangiography (left to right: intraoperative image under white light, capillary phase and venous phases of the FNa videoangiography). (K) Regular excitation (light blue) overlapping the emission (light green) laser light contains light only at 464 nm wavelength and does not interfere with the emission light; thus, the videoangiogram has good contrast. (L–N) An endoscope outfitted for FNa videoangiography. (L) A 2.7-mm straight endoscope is connected to a blue LED light source and a long-pass filter is inserted at the camera attachment. (M) The intraoperative view of endoscopic FNa videoangiography (left to right: under white light, under the blue LED before FNa injection, and after FNa injection). (N) The diagram showing optical setup of the device. Blue LED light is concentrated around 465 nm, and a long-pass filter (black line) allows green emission light into the camera. *, right posterior cerebral artery; **, left posterior cerebral artery; AN, aneurysm; BA, basilar artery; Max, maximum; Min, minimum; SCA, superior cerebellar artery. (A–C,H,K,L,N) are used with permission from Barrow Neurological Institute, Phoenix, Arizona. (D–G) Are used with permission from Suzuki et al. (37). (I) is copyright of Sato et al. (38) and made available under Creative Commons. (J) is used with permission from Ito et al. (22). (M) is used with permission from Hashimoto et al. (20).

Figure 3

Intraoperative images of an unruptured anterior communicating artery. (A) Intraoperative image under normal light. (B) Intraoperative image taken during FNa videoangiography; the aneurysm is not filling after being clipped (white arrow). Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Figure 4

Intraoperative images of a left frontal arteriovenous malformation (A) under normal light, (B) during FNa videoangiography, (C) during real-time inspection of the nidus and the deep feeders (white arrow) under FNa videoangiography during dissection, and (D) after total removal of the malformation. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Figure 5

FNa videoangiography images from a patient with moyamoya disease after a superficial temporal artery to middle cerebral artery bypass shows filling of (A) donor and recipient arteries, (B) cortical capillaries, and (C) all cortical vascular networks. Notice the filling starts at the bypass site and spreads around. Used with permission from Charite Universitätsmedizin Berlin, Berlin, Germany.