Tag: Fluorescein

Posted on

Fluorescein-guided resection of cerebral metastases is associated with greater tumor resection

Acta Neurochirurgica (2022) 164:451–457

Sodium fluorescein (fluorescein) crosses a disrupted blood-brain barrier similarly to gadolinium contrast in contrast-enhancing cerebral tumors. When exposed to light with 560 nm wavelength during surgery, fluorescein emits a yellow-green fluorescent light that can be visualized through an operating microscope equipped with an appropriate emission filter. The distribution of the fluorescence correlates with the contrast on a gadolinium contrast-enhanced MRI.

Objective The objective of this single-center retrospective study was to investigate if the use of fluorescein would increase the extent of resection and to examine if fluorescein guided resection influences postoperative neurological status.

Methods During the study period from August 2014 to August 2018, 117 patients were operated for cerebral metastases. Of these, 56 operations were guided by fluorescein and 61 by traditional white light. All patients had an early postoperative MRI within 72 h after surgery.

Results The use of fluorescein increased the extent of resection in patients with cerebral metastases. The use of fluorescein was not associated with increased postoperative sequelae or neurological damage regardless of underlying primary cancer.

Conclusion Fluorescein is a helpful supplement in the neurosurgical treatment of cerebral metastases.

Posted on

Ependymal fluorescence in fluorescence-guided resection of malignant glioma: a systematic review

Acta Neurochirurgica (2020) 162:365–372

Fluorescence in the ventricular wall or the ependyma during fluorescence-guided resection (FGR) of malignant glioma is commonly observed when malignant gliomas infiltrate the ventricles. However, the underlying pathophysiology and clinical importance are largely unknown but may play a role in deciding whether to continue resection into the ventricles or not. Here, we systematically review available data regarding ependymal fluorescence in FGR using five aminolevulinic acid (5-ALA) and sodium fluorescein (SF).

Methods A literature search on MEDLINE, EMBASE, and WEB OF SCIENCE was performed using the following headings and search operators: ependy* fluorescence AND (5-ALA OR five aminolevulinic acid), ventric* wall fluorescence AND (5- ALA OR five aminolevulinic acid), ependy* fluorescence AND fluorescein, and ventric* wall fluorescence AND fluorescein. Both authors analyzed abstracts independently. Included articles were further reviewed for prevalence of ependymal fluorescence, patterns of fluorescence, and histopathological characteristics of sampled tissues as well as radiological signs of ependymal fluorescence. Results are reported according to the PRISMA statement.

Results Of 202 records identified, 6 studies were included compiling a total number of 198 patients treated with FGR using 5- ALA. No study on ependymal fluorescence after administration of SF was found. Overall prevalence of ependymal fluorescence was 61.4%. A total of 54.5% of cases were found to be positive for tumor cells. A total of 25.5% of patients with ependymal fluorescence were related to contrast enhancement in ventricular walls.

Conclusions The phenomenon of ventricular wall fluorescence in 5-ALA-derived fluorescence-guided resection of malignant glioma is poorly understood and not always may fluorescence represent tumor infiltration. A larger scale prospective sampling study with molecular analyses is currently ongoing and will hopefully provide further insight into pathophysiology and clinical implications of ependymal fluorescence.

Posted on

Universal fluorescence module for intraoperative fluorescein angiography

Acta Neurochirurgica (2019) 161:1343–1348

Even in specialized centers, suboptimal aneurysm clipping can be as high as 12%. Intraoperative fluorescence angiography with indocyanine green and, more recently, fluorescein sodium have been shown to be a good method for intraop- erative flow assessment. However, the cost with the apparatus it entails limits its widespread use.

We have developed a low-cost universal fluorescence module (FM) designed to visualize fluorescein and perform intraoperative angiography. The purpose of this paper is to describe this device as well as to present our early experience with its use in the treatment of cerebral aneurysms.

Method A FM was designed and built using a cyan-blue narrow bandpass (460 to 490 nm) excitation filter and a yellow-orange longpass (blocking wavelengths under 520 nm) barrier filter mounted on a 3D-printed holding tray in a specific disposition to perfectly match the light source and the objective lens of the surgical microscope. It allowed switching from white light to fluorescence mode in a simple and sterile fashion. Its perfect attachment to the microscope was possible by reusing the lens fittings extracted from used original drape sets that would otherwise be discarded. Four patients underwent aneurysm clipping using the FM at two institutions from April to September 2018.

Results A bright green fluorescence against a dark background was observed after intravenous bolus of fluorescein. Blood vessels became obviously distinct from non-contrast-filled structures such as clipped aneurysms and the brain. Vascular anatomy could be appreciated without any distortion, including perforating arteries.

Conclusions Intraoperative fluorescence angiography was successfully performed with the use of this universal FM after intra- venous injection of fluorescein sodium. This simple and low-cost device may be useful in resource-limited centers, where other sorts of intraoperative angiography are not available.

Posted on

Sodium Fluorescein Facilitates Guided Sampling of Diagnostic Tumor Tissue in Nonenhancing Gliomas

Neurosurgery 82:719–727, 2018

Accurate tissue sampling in nonenhancing (NE) gliomas is a unique surgical challenge due to their intratumoral histological heterogeneity and absence of contrast enhancement as a guide for intraoperative stereotactic guidance. Instead, T2/fluid-attenuated inversion-recovery (FLAIR) hyperintensity on MRI is commonly used as an imaging surrogate for pathological tissue, but sampling from this region can yield nondiagnostic or underdiagnostic brain tissue. Sodium fluorescein is an intraoperative fluorescent dye that has a high predictive value for tumor identification in areas of contrast enhancement and NE in glioblastomas. However, the underlying histopathological alterations in fluorescent regions of NE gliomas remain undefined.

OBJECTIVE: To evaluate whether fluorescein can identify diagnostic tissue and differentiate regions with higher malignant potential during surgery for NE gliomas, thus improving sampling accuracy.

METHODS: Thirteen patients who presented with NE, T2/FLAIR hyperintense lesions suspicious for glioma received fluorescein (10%, 3 mg/kg intravenously) during surgical resection.

RESULTS: Patchy fluorescence was identified within the T2/FLAIR hyperintense area in 10 of 13 (77%) patients. Samples taken from fluorescent regions were more likely to demonstrate diagnostic glioma tissue and cytologic atypia (P < .05). Fluorescein demonstrated a 95% positive predictive value for the presence of diagnostic tissue. Samples from areas of fluorescence also demonstrated greater total cell density and higher Ki-67 labeling than nonfluorescent biopsies (P < .05).

CONCLUSION: Fluorescence in NE gliomas is highly predictive of diagnostic tumor tissue and regions of higher cell density and proliferative activity.

Posted on

Dual-labeling with 5–aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas

J Neurosurg 128:399–405, 2018

Fluorescence guidance with 5–aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue.

METHODS The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System).

RESULTS Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green braintissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection.

CONCLUSIONS Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

 

Posted on

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Acta Neurochir (2017) 159:151–167

Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all pre-clinically tested agents with the potential for FGS for glioma.

Methods: We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.

Results: The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5- aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.

Conclusions: 5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.

Posted on

A prospective comparative study of microscope-integrated intraoperative fluorescein and indocyanine videoangiography for clip ligation of complex cerebral aneurysms

A prospective comparative study of microscope-integrated intraoperative fluorescein and indocyanine videoangiography for clip ligation of complex cerebral aneurysms

J Neurosurg 122:618–626, 2015

The authors prospectively analyzed 2 microscope-integrated videoangiography techniques using intravenous indocyanine green (ICG) and fluorescein for assessment of cerebral aneurysm obliteration and adjacent vessel patency.

Methods The authors prospectively enrolled 22 patients who underwent clip ligation of their aneurysm and used intraoperative videoangiography to assess obliteration of the aneurysmal sac and patency of the adjacent branching and perforating arteries. Patients underwent ICG videoangiography (ICG-VA) and the newly developed fluorescein videoangiography (FL-VA) using microscope-integrated fluorescence modules. Two independent observers compared the videoangiography recordings for value and quality to assess aneurysm exclusion and the patency of adjacent arteries.

Results All 22 patients first underwent FL-VA and then ICG-VA after clip application. In 7 cases (32%), FL-VA provided superior detail to assess perforating arteries (4 cases), distal branches (2 cases), and both (1 case); such detail was not readily available on ICG-VA. In 1 patient, ICG-VA offered better visualization of posterior communicating artery aneurysm occlusion than FL-VA because of staining artifact on the aneurysm dome from the adjacent tentorium. In 2 patients, FL-VA offered the needed advantage of real-time manipulation of the vessels and flow assessment by visualization through the operating microscope oculars. In 2 other cases, ICG-VA was more practical for repeat usage because of its more efficient clearance from the intravascular space. The ICG-VA image quality was often degraded at higher magnification in deep operative fields, partly due to chromatic aberration. Both ICG-VA and FL-VA afforded restricted views of vasculature based on the angle of surgical approach and obscuration by blood clot, aneurysm, or brain tissue.

Conclusions Compared with ICG-VA, FL-VA can potentially provide an improved visualization of vasculature at high magnification in deep surgical fields. ICG-VA is more effective for repeated use during clip repositioning due to ICG’s minimal vascular wall extravasation. Therefore, in certain cases, FL-VA may offer some advantages and play a complementary role along with ICG-VA in intraoperative fluorescence evaluation during microsurgical management of aneurysms.

Posted on

A prospective study of microscope-integrated intraoperative fluorescein videoangiography during arteriovenous malformation surgery

intraoperative fluorescein videoangiography during arteriovenous malformation surgery

Neurosurg Focus 36 (2):E15, 2014

The authors report on the use of a recently developed microscope-integrated fluorescent module using low-dose intravenous fluorescein for videoangiography during arteriovenous malformation (AVM) surgery.

Methods. The authors analyzed the application of a low-dose intraoperative fluorescein in 4 consecutive patients undergoing AVM surgery. The ability to distinguish the associated vessels of the AVM from normal vessels and to assess the degree of AVM obliteration based on videoangiography of venous drainage was specifically analyzed.

Results. All 4 patients underwent fluorescein angiography without complication. In each case, videoangiography confirmed recognition of feeding arteries and draining veins through the operating oculars under the fluorescent mode. In one case involving a large frontal AVM, videoangiography demonstrated mainly cortical veins on the surface of the AVM and alerted the senior author to first tackle the feeding arteries in the interhemispheric space. While evaluating the flow within the different draining veins after most of the AVM was disconnected, videoangiography also prioritized the order for disconnection of large draining veins to allow mobilization the AVM and exposure of the remaining deep arterial feeders. In the other 3 cases, videoangiography allowed easy recognition of the angioarchitecture of the AVMs, estimated its cortical boundaries, and most importantly, assessed the flow within the draining veins before their disconnection.

Conclusions. The authors found fluorescein videoangiography to be a useful adjunct in resection of AVMs. This technology offers the unique ability to visualize fluorescent vessels and nonfluorescent tissues in near-natural colors simultaneously and permits microsurgical manipulation of relevant structures under the fluorescent mode. Largerscale studies are needed to establish its efficacy and wider applicability.

Posted on

Intraoperative fluorescence for resection of hemangioblastomas

Intraoperative fluorescence for resection of hemangioblastomas

Acta Neurochir (2013) 155:1287–1292

Resection of hemangioblastomas can be challenging due to their high vascularity and intimate association with neighboring cerebrovascular structures. The authors present their intraoperative findings using fluorescein angiography and fluorescence for removal of hemangioblastomas in an attempt to improve the safety and extent of resection.

Methods From April through August 2012, four patients were diagnosed with hemangioblastomas, 3 in the cerebellum and 1 in the medulla oblongata. Low-dose (4 mg/kg) sodium fluorescein was injected intravenously immediately before microdissection. The area of interest was inspected through a microscope-integrated fluorescent module.

Results In three superficially located tumors, the vascular pattern of feeding and draining vessels could be easily identified with fluorescein angiography. The resection of the tumors was guided using real-time fluorescence mode. For each patient, histopathologic examination of the lesion confirmed the diagnosis of hemangioblastoma. All samples of fluorescent tissue resected were confirmed to contain tumor. No patient experienced any complication.

Conclusion Low-dose sodium fluorescein used in conjunction with a microscope-integrated fluorescence module is a potentially useful tool for localization, vascular characterization, and resection of hemangioblastomas.

Proudly powered by WordPress