Fluorescein Angiography in Intracranial Aneurysm Surgery: A Helpful Method to Evaluate the Security of Clipping and Observe Blood Flow

doi:10.1016/j.wneu.2017.05.172

World Neurosurgery

Volume 105, September 2017, Pages 406-411

https://doi.org/10.1016/j.wneu.2017.05.172 Get rights and content

Background

In cerebral aneurysm surgery, various tools are used to evaluate blood flow, including Doppler ultrasonography, conventional cerebral angiography, and electrophysiological monitoring. Fluorescein and indocyanine green are widely used in vascular and central nervous system tumor neurosurgery; however, their routine utilization in aneurysmal surgery is uncommon, despite the fact that they allow direct visualization of blood flow after aneurysmal sac occlusion, enabling the observation of vessel permeability and the effectiveness of aneurysmal obliteration. We report our initial experience using fluorescein video angiography as a control measure for proper clip placement and control of blood flow in aneurysm surgery, and review the relevant literature.

Methods

This pilot study presents an initial experience, with enrollment of 10 patients harboring a total of 12 cerebral aneurysms who underwent surgery via clipping and subsequent fluorescence videoangiography control. The intravenous injection was performed to demonstrate the patency of the arteries adjacent to the aneurysm.

Results

Following intravenous injection, fluorescein sodium remains in the cerebral vasculature for approximately 3 minutes, providing ample time to evaluate vessel patency and determine whether clip repositioning is needed. None of the patients experienced complications during intravenous injection of fluorescein sodium, and the patency of surrounding vessels was demonstrated in all cases.

Conclusions

Fluorescein injection in itself does not present a risk of complications, is simple to use, and offers a clear image of the cerebral vasculature. Thus, this technique is useful for determining vessel patency and the degree of aneurysmal occlusion.

Introduction

In cerebral aneurysm surgery, it is useful to confirm aneurysm obliteration and the patency of adjacent arteries.¹ To view the blood flow in the vessels that surround the aneurysm, various intraoperative methods are utilized, such as Doppler ultrasonography, conventional cerebral angiography, and electrophysiological monitoring.²

Along with these methods, the literature describes intraoperative videoangiography (VA) using fluorescein sodium (FL) or indocyanine green (ICG) as the dye.2, 3, 4 Several studies have specifically addressed the utility of fluorescein in cerebral aneurysm surgery.2, 5 This technique can be highly useful for demonstrating the patency of parent arteries and determining whether an aneurysm is completely occluded.² Aside from vascular surgery, fluorescein sodium is also currently being tested as an intraoperative guidance agent in the resection of high-grade gliomas.⁶

Neurosurgical centers, especially those with limited resources, require cost-effective tools in order to evaluate the quality of aneurysm surgery. Although extensive research has been published on the use of ICG-VA for assessment of proper aneurysm clipping and blood flow, data on the use of FL-VA in aneurysm surgery remains limited.⁷ The purpose of this article is to present our initial experience on using FL-VA, review the relevant literature and offer some suggestions on its utilization to other surgeons who want to adopt it.

Section snippets

Methods

Ten consecutive patients (7 females and 3 males) were enrolled in this study (Table 1). The inclusion criteria were subarachnoid hemorrhage (SAH) as a result of ruptured cerebral aneurysms and a Hunt and Hess (H&H) score of 1 to 4. The exclusion criteria were the lack of an SAH from a ruptured cerebral aneurysm and patients with SAH secondary to ruptured cerebral aneurysms with an H&H score of 5. Within this series, 12 aneurysms were diagnosed, with 9 patients harboring a single aneurysm and 1

Results

All of the patients enrolled in this pilot study received an intraoperative intravenous bolus of 5 mL of 10% fluorescein sodium immediately after aneurysm clipping. At approximately 15 seconds postinjection, the major cerebral vessels exhibited a yellowish-green tint in the yellow 560 light. In all cases except one (case 1; Figure 1), the aneurysm was properly occluded, whereas the neighboring arteries were permeable. In case 1, fluorescein injection demonstrated inappropriate clip placement,

Discussion

Here we present our initial experience with the use of FL-VA. Although the literature on the use of ICG-VA in aneurysm surgery has grown exponentially, the number of studies on FL-VA remains limited.⁷ Our pilot study shows that fluorescein can be a good compromise solution for neurosurgical centers with limited resources with no other means to demonstrate complete aneurysm occlusion and satisfactory restoration of blood flow.

As mentioned above, numerous methods are available for evaluating

Conclusions

FL-VA is a practical intraoperative tool that can demonstrate occlusion of an aneurysmal sac and reveal the patency of cerebral vessels surrounding the aneurysm after clipping. This procedure is low risk and can be implemented as a routine examination in vascular neurosurgery. An important advantage for FL-VA is that it can be performed without interrupting the surgical procedure and is useful in decreasing surgical complications. Based on our findings, we recommend the use of FL-VA to improve

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Cited by (20)

Avoiding Complications in Aneurysm Ligation: Operative Tips and Tricks
2022, World Neurosurgery
Citation Excerpt :
Another fluorophore agent available for intraoperative VA is fluorescein sodium (FNa). Although its first use in vascular neurosurgery dates before the use of ICG,53 to date, only few clinical series have assessed the role of this fluorophore agent in the treatment of intracranial aneurysms.54-61 FNa-VA, commonly available in modern neurosurgical microscopes, may overcome some of the difficulties with ICG-VA.
Preventing possible complications during brain aneurysm surgery is mandatory to ensure a better outcome for patients. Currently, it is possible to rely on some technologic innovations such as motor evoked potential, endoscope-assisted surgery, dye with indocyanine green, and video angiography capable of supporting the surgeon's work. The innovation process has mainly assisted the endovascular technique compared with surgery. The latter, apart from some new technical expedients, always requires anatomic knowledge and optimal technical preparation. A careful patient selection, adequate surgical exposure, use of microsurgical techniques in expert hands, and meticulous postoperative management represent the key to success for the surgical treatment of cerebral aneurysms.
Intra-operative fluorescein videoangiography-related nephrotoxicity in intracranial aneurysm surgery: Single center, observational cohort study
2021, Clinical Neurology and Neurosurgery
Intra-operative fluorescein video angiography (FL-VA) has been given increasing attention recently and several studies reported its high utility in neurovascular surgery. The aim of this study was to evaluate the safety of FL-VA in a prospective, single-center cohort of patients operated due to cerebral aneurysms.
This is an observational cohort study including 150 patients operated due to intracranial aneurysms. The study group consisted of 70 consecutive patients operated with the use of fluorescein video angiography. Post-operative acute kidney injury (AKI) occurrence as well as systemic adverse reactions were reported and further compared with 80 matched controls where FL-VA was not used. Statistical analysis was performed using non-parametric tests (Fisher’s exact test).
Post-operative AKI was observed in 17,1% of patients in the study group with only half presenting with acute functional impairment. All of these patients presented initially due to aneurysm rupture. Pre-existing renal dysfunction and hypertension occurred in 16,7% and 33,3%, respectively. No systemic complications following FL-VA were reported. When compared to matched controls, no statistically significant difference regarding AKI occurrence was observed between these two patient populations.
Intra-operative fluorescein video angiography proved to have a good safety profile in our cohort. The results of this study suggest that post-operative acute kidney injury observed in patients with subarachnoid hemorrhage is not related to fluorescein use.
Intraoperative Fluorescein Sodium Videoangiography in Intracranial Aneurysm Surgery
2021, World Neurosurgery
Citation Excerpt :
First introduced to neurosurgery in 1967, FNa is another fluorophore agent available for VA.5 FNa was applied to the treatment of intracranial aneurysms in 19946; however, there is no report to our knowledge focusing on the use of FNa in vascular neurosurgery until FNa-VA was discussed in the article by Suzuki et al. in 2007.13 Since then, only a handful of clinical series have been published focusing on the use of FNa-VA in clip ligation of intracranial aneurysm surgery.7,8,10,11,17 In contrast to the limited use of FNa in vascular neurosurgery, FNa-VA, commonly available in modern neurosurgical microscopes, such as YELLOW 560 (Carl Zeiss Meditec AG) and FL560 fluorescence modules, may overcome some of the difficulties with ICG-VA.
Fluorescein sodium (FNa) videoangiography (VA) was performed to evaluate blood flow within vessels and exclusion of the aneurysm after surgical clipping of intracranial aneurysms. The aim of this study was to report results of FNa-VA in a case series, including benefits and limitations of the technique, and compare intraoperative findings with postoperative cerebral angiography to assess reliability of FNa-VA.
The study included 64 aneurysms in 50 consecutive patients. Following clip ligation of the aneurysm, 100 mg of FNa was administered intravenously. The microscope light was switched to the FL560 integrated fluorescence module. Aneurysm sac, parent arteries, and perforating arteries were observed.
FNa-VA promoted real-time assessment of the surgical field in three-dimensional view through the binoculars with good image quality. In 79.68% of aneurysms, FNa-VA confirmed satisfactory clip application, as FNa did not penetrate into the aneurysm. In 14.06% of aneurysms, a homogeneous yellow-green color change occurred, which was accepted as a false-positive sign. In 6.25% of aneurysms, FNa seeped into the aneurysm emitting a heterogeneous green signal, which slowly dispersed throughout the sac. Postoperative angiography revealed satisfactory results. Small neck remnants were present in 5 patients, and mild parent artery stenosis was found in 3 patients. No ischemic event occurred secondary to parent artery or perforating artery occlusion.
FNa-VA adds greatly to the safety of surgical treatment of intracranial aneurysms, particularly in lesions situated in deep locations, by enabling real-time inspection, which facilitates safer manipulation and evaluation of structures in question.
Excited state dipole moment of the fluorescein molecule estimated from electronic absorption spectra
2019, Journal of Molecular Structure
Citation Excerpt :
Thus, a microscope-integrated fluorescence module renders fluorescein fluorescence technology is a valuable tool in the surgical management of neoplastic and vascular lesions [29]. This technique allows to maximize the resection of tumors and perform intraoperative angiography to guide microsurgical management of aneurysms and arteriovenous malformations [30,31]. A comprehensive review on the fluorescein-guided surgery of malignant gliomas can be found in Ref. [32].
The solvatochromic study of fluorescein is performed in order to obtain information on both the interactions with solvents in which it is dissolved and the electro-optical parameters of the molecule in the first excited electronic state. The shifts of the visible absorption spectral band of fluorescein dissolved in several solvents were experimentally measured and correlated to solvent parameters such as the refractive index, electrical permittivity and the Kamlet-Taft parameters (hydrogen bond acidity and basicity, respectively). A quantum-mechanical study of the fluorescein molecule was additionally performed to determine some parameters of the fluorescein molecule in the ground electronic state. Following McRae's hypothesis, according to which the molecular polarizability does not change in the absorption process, the data obtained from the solvatochromic analysis and quantum-mechanical calculations were corroborated in order to estimate the dipole moment of fluorescein in its first excited electronic state.
Residual Cerebral Aneurysms After Microsurgical Clipping: A New Scale, an Agreement Study, and a Systematic Review of the Literature
2019, World Neurosurgery
The surgical repair of a cerebral aneurysm does not always lead to complete occlusion. A standardized repeatable method of reporting results of surgical clipping is desirable. Our purpose was to systematically review methods of classifying aneurysm remnants, provide a new scale with precise definitions of categories, and perform an agreement study to assess the variability in adjudicating remnants after aneurysm clipping.
A systematic review was performed to identify ways to report angiographic results of surgical clipping between 1963 and 2017. Postclipping angiographic results of 43 patients were also independently evaluated by 10 raters of various experience and backgrounds using a new 4-category scale. Agreement between responses were analyzed using κ statistics.
The systematic review yielded 63 articles with 37 different nomenclatures using 2–6 categories. The reliability of judging the presence of an aneurysm remnant on catheter angiography was studied only twice, with only 2 raters each time, with contradictory results. Interobserver agreement using the new 4-category scale was moderate (κ = 0.52; 95% confidence interval, 0.43–0.62) for all observers, but improved to substantial (κ = 0.62; 95% confidence interval, 0.47–0.76) when results were dichotomized (grade 0/1 vs. 2/3).
Various classification schemes to evaluate angiographic results after surgical clipping exist in the literature, but they lack standardization. Adjudication using fewer, better defined categories may yield more reliable agreement.
Diagnostic Accuracy of a Confocal Laser Endomicroscope for In Vivo Differentiation Between Normal Injured And Tumor Tissue During Fluorescein-Guided Glioma Resection: Laboratory Investigation
2018, World Neurosurgery
Citation Excerpt :
Fluorescein sodium (FNa), a drug approved by the U.S. Federal Drug Administration (FDA), is administered off-label to patients in fluorescence-guided resection of brain tumors using intraoperative imaging technology that can detect its emitted fluorescence. The use of FNa dates back to 19484; since then, its use in brain5-15 and spinal cord16 tumor surgery, brain abscesses,17,18 cerebrospinal fluid leaks,19,20 and cerebrovascular angiography application21-25 has been investigated and reviewed in multiple studies.26-29 For tumor application, FNa is administered intravenously at dosages of 2 to 20 mg/kg and accumulates in and around tumor tissue because of the disruption of the blood–brain barrier in this tissue.3
Glioma resection with fluorescein sodium (FNa) guidance has a potential drawback of nonspecific leakage of FNa from nontumor areas with a compromised blood–brain barrier. We investigated the diagnostic accuracy of in vivo confocal laser endomicroscopy (CLE) after FNa administration to differentiate normal brain, injured normal brain, and tumor tissue in an animal glioma model.
GL261-Luc2 gliomas in C57BL/6 mice were used as a brain tumor model. CLE images of normal, injured normal, and tumor brain tissues were collected after intravenous FNa administration. Correlative sections stained with hematoxylin and eosin were taken at the same sites. A set of 40 CLE images was given to 1 neuropathologist and 3 neurosurgeons to assess diagnostic accuracy and rate image quality (1–10 scale). Additionally, we developed a deep convolution neural network (DCNN) model for automatic image classification.
The mean observer accuracy for correct diagnosis of glioma compared with either injured or uninjured brain using CLE images was 85%, and the DCNN model accuracy was 80%. For differentiation of tumor from nontumor tissue, the experts' mean accuracy, specificity, and sensitivity were 90%, 86%, and 96%, respectively, with high interobserver agreement overall (Cohen κ = 0.74). The percentage of correctly identified images was significantly higher for images with a quality rating >5 (104/116, 90%) than for images with a quality rating ≤5 (32/44, 73%) (P = 0.007).
With sufficient FNa present in tissues, CLE was an effective tool for intraoperative differentiation among normal, injured normal, and tumor brain tissue. Clinical studies are warranted to confirm these findings.

View all citing articles on Scopus

: Conflict of interest statement: This study was supported by POSDRU (HRDSOP) Grant 159/1.5/S/138776. The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Original ArticleFluorescein Angiography in Intracranial Aneurysm Surgery: A Helpful Method to Evaluate the Security of Clipping and Observe Blood Flow

Background

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Neurochirurgie

World Neurosurg

Intra-arterial fluorescence angiography with injection of fluorescein sodium from the superficial temporal artery during aneurysm surgery: technical notes

Neurol Med Chir (Tokyo)

Confirmation of blood flow in perforating arteries using fluorescein cerebral angiography during aneurysm surgery

J Neurosurg

Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow

Neurosurgery

Intraoperative assessment of aneurysm clip placement by intravenous fluorescein angiography

Neurosurgery

Intra-arterial injection fluorescein videoangiography in aneurysm surgery

Neurosurgery

Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance

J Neurosurg

Editorial: Clipping of neurosurgical aneurysms: the dye is cast

J Neurosurg

Development of and clinical experience with a simple device for performing intraoperative fluorescein fluorescence cerebral angiography: technical notes

Neurol Med Chir (Tokyo)

Intraoperative microvascular Doppler sonography in aneurysm surgery

Minim Invasive Neurosurg

Intraoperative microvascular Doppler ultrasonography in cerebral aneurysm surgery

J Neurol Neurosurg Psychiatry

Original Article
Fluorescein Angiography in Intracranial Aneurysm Surgery: A Helpful Method to Evaluate the Security of Clipping and Observe Blood Flow