Is Intraoperative Pathology Needed if 5-Aminolevulinic-Acid-Induced Tissue Fluorescence Is Found in Stereotactic Brain Tumor Biopsy?

Neurosurgery, Volume 86, Issue 3, March 2020, Pages 366–373

Intraoperative histopathology and acquisition of multiple tissue samples in stereotactic biopsies results in a prolonged length of surgery and potentially increased complication rate.
OBJECTIVE
To investigate the clinical benefits of a novel strategy for stereotactic brain tumor biopsies with the assistance of 5-aminolevulinic acid (5-ALA) induced fluorescence.
METHODS
Patients that received 5-ALA prior to stereotactic biopsy of a suspected brain tumor were included. According to our strategy, the procedure was terminated in the case of strong fluorescence of the biopsy samples. In contrast, intraoperative histology was demanded in the case of vague/no fluorescence. Length of surgery, number of biopsy samples, diagnostic rate, and periprocedural complications were compared between these 2 groups.
RESULTS
Altogether, 79 patients were included, and strong fluorescence was present in 62 cases (79%), vague fluorescence was in 4 cases (5%), and no fluorescence was in 13 cases (16%). The diagnostic rate was comparable in biopsies with strong fluorescence without intraoperative histopathology and cases with vague/no fluorescence with intraoperative histopathology (98% vs 100%; P = 1.000). A significantly shorter length of surgery (41 vs 77 min; P < .001) and reduced average number of biopsy samples (3.6 vs 4.9; P = .011) was found in patients with strong compared to vague/no fluorescence. However, no statically significant difference in periprocedural complications between cases with strong and vague/no fluorescence was found (7% vs 18%; P = .166).
CONCLUSION
Our data demonstrate the clinical benefits of a novel strategy for stereotactic brain tumor biopsies with assistance of 5-ALA. Thus, this biopsy strategy will increase the efficiency of this standard neurosurgical procedure in the future.

Intraoperative 3D ultrasound–guided resection of diffuse low-grade gliomas

J Neurosurg 132:518–529, 2020

Extent of resection (EOR) and residual tumor volume are linked to prognosis in low-grade glioma (LGG) and there are various methods for facilitating safe maximal resection in such patients. In this prospective study the authors assess radiological and clinical results in consecutive patients with LGG treated with 3D ultrasound (US)–guided resection under general anesthesia.

METHODS Consecutive LGGs undergoing primary surgery guided with 3D US between 2008 and 2015 were included. All LGGs were classified according to the WHO 2016 classification system. Pre- and postoperative volumetric assessments were performed, and volumetric results were linked to overall and malignant-free survival. Pre- and postoperative health-related quality of life (HRQoL) was evaluated.

RESULTS Forty-seven consecutive patients were included. Twenty LGGs (43%) were isocitrate dehydrogenase (IDH)– mutated, 7 (14%) were IDH wild-type, 19 (40%) had both IDH mutation and 1p/19q codeletion, and 1 had IDH mutation and inconclusive 1p/19q status. Median resection grade was 93.4%, with gross-total resection achieved in 14 patients (30%). An additional 24 patients (51%) had small tumor remnants < 10 ml. A more conspicuous tumor border (p = 0.02) and lower University of California San Francisco prognostic score (p = 0.01) were associated with less remnant tumor tissue, and overall survival was significantly better with remnants < 10 ml (p = 0.03). HRQoL was maintained or improved in 86% of patients at 1 month. In both cases with severe permanent deficits, relevant ischemia was present on diffusionweighted postoperative MRI.

CONCLUSIONS Three-dimensional US–guided LGG resections under general anesthesia are safe and HRQoL is preserved in most patients. Effectiveness in terms of EOR appears to be consistent with published studies using other advanced neurosurgical tools. Avoiding intraoperative vascular injury is a key factor for achieving good functional outcome.

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.

Interlaminar contralateral endoscopic lumbar foraminotomy assisted with the O-arm navigation

Acta Neurochirurgica (2020) 162:121–125

The interlaminar contralateral endoscopic lumbar foraminotomy (ICELF) provides access to the foraminal pathology with less violation to facet than the ipsilateral approach. However, it is technically challenging even for an experienced surgeon.

Methods We introduce the step-by-step workflow of the interlaminar contralateral endoscopic lumbar foraminotomy assisted with O-arm navigation system.

Conclusion The ICELF assisted with O-arm navigation is safe, accurate, and efficient for the treatment of lumbar foraminal stenosis. The CT-based navigation reshapes the learning curve of the advanced endoscopic technique, reducing the risk of facet joint violation, and minimizes radiation exposure to surgeons.

3D ultrasound–guided resection of low-grade gliomas: principles and clinical examples

Neurosurg Focus 47 (6):E9, 2019

3D ultrasound (US) is a convenient tool for guiding the resection of low-grade gliomas, seemingly without deterioration in patients’ quality of life.

This article offers an update of the intraoperative workflow and the general principles behind the 3D US acquisition of high-quality images.

The authors also provide case examples illustrating the technique in two small mesial temporal lobe lesions and in one insular glioma. Due to the ease of acquiring new images for navigation, the operations can be guided by updated image volumes throughout the entire course of surgery.

The high accuracy offered by 3D US systems, based on nearly realtime images, allows for precise and safe resections. This is especially useful when an operation is performed through very narrow transcortical corridors.

5-Aminolevulinic Acid Fluorescence-Guided Resection of 18F-FET-PET Positive Tumor Beyond Gadolinium Enhancing Tumor Improves Survival in Glioblastoma

Neurosurgery 85:E1020–E1029, 2019

The value of early postoperative 18F-FET-PET in patients with glioblastoma (GBM) is unclear. Five-aminolevulinic acid (5-ALA) is used for fluorescence-guided resections in these patients and previous data suggest that fluorescence and 18F-FET-PET both demarcate larger tumor volumes than gadolinium enhanced magnet resonance imaging (MRI).

OBJECTIVE: To correlate fluorescence with enhancing volumes on postoperative MRI and 18F-FET-PET tumor volumes, and determine the value of postoperative 18F-FET-PET for predicting survival through observational study.

METHODS: GBM patients underwent fluorescence-guided resection after administration of 5-ALA followed by early postoperative MRI and 18F-FET-PET for determination of residual tissue volumes. All patients were treated with standard temozolomide radiochemotherapy and monitored for progression-free and overall survival (PFS, OS).

RESULTS: A total of 31 patients were included. For functional reasons, residual 5-ALA derived fluorescent tissue was left unresected in 18 patients with a median 18F-FETPET volume of 17.82 cm3 (interquartile range 6.50-29.19). In patients without residual fluorescence, median 18F-FET-PET volume was 1.20 cm3 (interquartile range 0.87-5.50) and complete resection of gadolinium enhancing tumor was observed in 100% of patients. A 18F-FET-PET volume of above 4.3 cm3 was associated with worse OS (logrank P-value≤.05), also in patients with no residual contrast enhancing tumor on MRI. More patients in whom fluorescencing tissue had been removed completely had postoperative 18F-FET-PET tumor volumes below 4.3 cm3.

CONCLUSION: Postoperative 18F-FET-PET volumes predict OS and PFS. Resection of 5-ALA derived fluorescence beyond gadolinium enhancing tumor tissue leads to lower postoperative 18F-FET-PET tumor volumes and improved OS and PFS without additional deficits.

Indocyanine green fluorescence video angiography reduces vascular injury–related morbidity during micro-neurosurgical clipping of ruptured cerebral aneurysms: a retrospective observational study

Acta Neurochirurgica (2019) 161:2397–2401

Specific procedural complications in aneurysm surgery are broadly related to vascular territory compromise and brain/nerve retraction; vascular complications account for about half of this. Intraoperative indocyanine green video angiography (ICG-VA) provides real-time high spatial resolution imaging of the cerebrovascular architecture, allowing immediate quality assurance of aneurysm occlusion and vessel integrity. The aim of this study was to examine whether the routine use of ICG-VA reduced early procedural complications related to vascular compromise or injury during micro-neurosurgical clipping of ruptured cerebral aneurysms.

Methods Retrospective comparative observational study of 412 adult good-grade (WFNS 1 or 2) SAH patients who had undergone microsurgical clipping without (n = 200, 2001–2004) or with (n = 212, 2009–2015) ICG-VA in a high-volume neurosurgical centre.

Results The ICG-VA group had a significantly lower incidence of procedural vascular complications (7/212; 3.3%) compared with the non-ICG-VA group (19/200; 9.5%) (Fisher’s exact test p = 0.0137).

Conclusions ICG-VA is a straightforward, easy-to-use, intraoperative adjunct which significantly reduces avoidable ‘technical error’ related morbidity.

Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma

J Neurosurg 131:724–734, 2019

The use of the optical contrast agent sodium fluorescein (NaFl) to guide resection of gliomas has been under investigation for decades. Although this imaging strategy assumes the agent remains confined to the vasculature except in regions of blood-brain barrier (BBB) disruption, clinical studies have reported significant NaFl signal in normal brain tissue, limiting tumor-to-normal contrast. A possible explanation arises from earlier studies, which reported that NaFl exists in both pure and protein-bound forms in the blood, the former being small enough to cross the BBB. This study aims to elucidate the kinetic binding behavior of NaFl in circulating blood and its effect on NaFl accumulation in brain tissue and tumor contrast. Additionally, the authors examined the blood and tissue kinetics, as well as tumor uptake, of a pegylated form of fluorescein selected as a potential optical analog of gadolinium-based MRI contrast agents.

METHODS Cohorts of mice were administered one of the following doses/forms of NaFl: 1) high human equivalent dose (HED) of NaFl, 2) low HED of NaFl, or 3) pegylated form of fluorescein. In each cohort, groups of animals were euthanized 15, 30, 60, and 120 minutes after administration for ex vivo analysis of fluorescein fluorescence. Using gel electrophoresis and fluorescence imaging of blood and brain specimens, the authors quantified the temporal kinetics of bound NaFl, unbound NaFl, and pegylated fluorescein in the blood and normal brain tissue. Finally, they compared tumor-to-normal contrast for NaFl and pegylated-fluorescein in U251 glioma xenografts.

RESULTS Administration of NaFl resulted in the presence of unbound and protein-bound NaFl in the circulation, with unbound NaFl constituting up to 70% of the signal. While protein-bound NaFl was undetectable in brain tissue, unbound NaFl was observed throughout the brain. The observed behavior was time and dose dependent. The pegylated form of fluorescein showed minimal uptake in brain tissue and improved tumor-to-normal contrast by 38%.

CONCLUSIONS Unbound NaFl in the blood crosses the BBB, limiting the achievable tumor-to-normal contrast and undermining the inherent advantage of tumor imaging in the brain. Dosing and incubation time should be considered carefully for NaFl-based fluorescence-guided surgery (FGS) of glioma. A pegylated form of fluorescein showed more favorable normal tissue kinetics that translated to higher tumor-to-normal contrast. These results warrant further development of pegylated-fluorescein for FGS of glioma.

Is Visible Aminolevulinic Acid-Induced Fluorescence an Independent Biomarker for Prognosis in Histologically Confirmed (World Health Organization 2016) Low-Grade Gliomas?

Neurosurgery, Volume 84, Issue 6, June 2019, Pages 1214–1224

Approximately 20% of low-grade gliomas (LGG) display visible protoporphyrin fluorescence during surgery after 5-aminolevulinic acid (5-ALA) administration.

OBJECTIVE: To determine if fluorescence represents a prognostic marker in LGG.

METHODS: Seventy-four consecutive patients with LGG (World Health Organization 2016) were operated on with 5-ALA. Fluorescent tissue was specifically biopsied. Tumor size, age, Karnofsky index, contrast-enhancement, fluorescence, and molecular factors (IDH1/IDH2-mutations, Ki67/MIB1 Index, 1p19q codeletions, ATRX, EGFR, p53 expression, and O6-methylguanine DNA methyltransferase promotor methylation), were related to progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS).

RESULTS: Sixteen of seventy-four LGGs (21.6%) fluoresced. Fluorescence was partially related to weak enhancement on magnetic resonance imaging and increased (positron emission tomography)PET-FET uptake, but not to Karnofsky Performance Score, tumor size, or age. Regarding molecular markers, only EGFR expression differed marginally (fluorescing vs nonfluorescing: 19% vs 5%; P = .057). Median follow-up was 46.4 mo (95% confidence interval [CI]: 41.8-51.1). PFS, MTFS, and OS were shorter in fluorescing tumors (PFS: median 9.8 mo, 95% CI: 1.00-27.7 vs 45.8, 31.9-59.7, MTFS: 43.0 [27.5-58.5] vs 64.6 [57.7- 71.5], median not reached, P = .015; OS: 51.6, [34.8-68.3] vs [68.2, 62.7-73.8], P = .002). IDH mutations significantly predicted PFS, MTFS, and OS. In multivariate analysis IDH status and fluorescence both independently predictedMTFS and OS. PFSwas not independently predicted by fluorescence.

CONCLUSION: This is the first report investigating the role of ALA-induced fluorescence in histologically confirmed LGG. Fluorescence appeared to be a marker for inherent malignant transformation and OS, independently of known prognostic markers. Fluorescence in LGG might be taken into account when deciding on adjuvant therapies.

ioCT-guided percutaneous radiofrequency ablation for trigeminal neuralgia

Acta Neurochirurgica (2019) 161:935–938

Percutaneous trigeminal nerve rhizotomy is usually performed by free-handed puncture of the foramen ovale under radiographic control with the patient kept semiconscious. The procedure has thus been reported to be highly uncomfortable for both the patient and surgeon. To our knowledge, this is the first description of a technique that includes precise navigated, CTguided puncture of the foramen with the patient in general anesthesia and confirmation of needle placement by intraoperative CT.

Method: Radiofrequency ablation of the trigeminal nerve was guided by intraoperative CT navigation with neuromonitoring of trigeminal nerve function. The patient was kept under general anesthesia during the procedure.

Conclusion: CT-guided percutaneous trigeminal nerve rhizotomy is a safe and efficient treatment strategy for the management of trigeminal neuralgia without the need of the patient being in a semiconscious state. Keywords Intraoperative computed tomography . Trigeminal neuralgia . Percutaneous rhizotomy . Radiofrequency thermocoagulatio

Advances in intraoperative brain mapping

Neurosurg Focus 45 (Suppl2):Intro, 2018

In the last decade, there has been significant interest among neurosurgeons in intraoperative brain mapping in cases of lesions in eloquent cortex and subcortical regions. This has occurred because foundational studies have provided strong evidence for the value of maximal safe resection of glioma.

Further evidence of the important role of cortical and subcortical stimulation mapping in achieving a safe, maximal resection has come forth.

Clinicians are also becoming aware of the limitations of preoperative imaging studies for definitive intraoperative decision-making.
Preoperative mapping techniques are commonly used, but the extent to which they are relied upon is quite variable.

In some centers, preoperative imaging techniques are used to guide the decision to choose cortical stimulation mapping, in other centers, it directs where the mapping may start, and in others, it is used in case the intraoperative mapping is ambiguous. It should be noted that there is significant variability in techniques in obtaining and processing this functional imaging data. Surgeons should become familiar both with this variability in general and with the protocols at their own center before relying on functional imaging for crucial decision-making.

In this issue of Neurosurgical Focus, we are pleased to show some of the recent advances and new applications of intraoperative brain mapping.
A variety of techniques and protocols are discussed in this issue. A variety of pathologies, including glioma, metastatic tumor, vascular lesions, and epileptic foci, are addressed through transcortical, trans-sylvian, transventricular, and intrahemispheric routes. The common theme in each of these cases is to apply cortical and subcortical stimulation in at-risk areas in order to minimize risk and maximize resection.

Readers should take note of stimulation parameters in each video and understand that there is practice variability that has evolved in each center. Whether a center is using monopolar or bipolar stimulation (or both), electrocorticography or not, common themes include careful observation and recording of stimulation response after escalation of intensity in a well-organized operative plan. Resection of the lesion is then performed, with the patient awake, or monitored, until the lesion is out or until the early onset of a new deficit. This careful monitoring is essential for safety and avoiding anything more than a temporary deficit.

Important tips for comfortable and safe awake surgical techniques are also a common theme in the video cases in this issue.
Finally, emerging technologies and older technologies, such as transcranial magnetic stimulation and subdural grid mapping, are discussed, along with advantages and disadvantages.
This month’s issue shows an excellent cross-section of the variety of contemporary applications of cortical stimulation mapping. We would like to thank the authors for their outstanding contributions to the field.

Use of the Airo mobile intraoperative CT system versus the O-arm for transpedicular screw fixation in the thoracic and lumbar spine

J Neurosurg Spine 29:397–406, 2018

Navigation-enabling technology such as 3D-platform (O-arm) or intraoperative mobile CT (iCT-Airo) systems for use in spinal surgery has considerably improved accuracy over that of traditional fluoroscopy-guided techniques during pedicular screw positioning. In this study, the authors compared 2 intraoperative imaging systems with navigation, available in their neurosurgical unit, in terms of the accuracy they provided for transpedicular screw fixation in the thoracic and lumbar spine.

METHODS The authors performed a retrospective analysis of clinical and surgical data of 263 consecutive patients who underwent thoracic and lumbar spine screw placement in the same center. Data on 97 patients who underwent surgery with iCT-Airo navigation (iCT-Airo group) and 166 with O-arm navigation (O-arm group) were analyzed. Most patients underwent surgery for a degenerative or traumatic condition that involved thoracic and lumbar pedicle screw fixation using an open or percutaneous technique. The primary endpoint was the proportion of patients with at least 1 screw not correctly positioned according to the last intraoperative image. Secondary endpoints were the proportion of screws that were repositioned during surgery, the proportion of patients with a postoperative complication related to screw malposition, surgical time, and radiation exposure. A blinded radiologist graded screw positions in the last intraoperative image according to the Heary classification (grade 1–3 screws were considered correctly placed).

RESULTS A total of 1361 screws placed in 97 patients in the iCT-Airo group (503 screws) and in 166 in the O-arm group (858 screws) were graded. Of those screws, 3 (0.6%) in the iCT-Airo group and 4 (0.5%) in the O-arm group were misplaced. No statistically significant difference in final accuracy between these 2 groups or in the subpopulation of patients who underwent percutaneous surgery was found. Three patients in the iCT-Airo group (3.1%, 95% CI 0%–6.9%) and 3 in the O-arm group (1.8%, 95% CI 0%–4.0%) had a misplaced screw (Heary grade 4 or 5). Seven (1.4%) screws in the iCT-Airo group and 37 (4.3%) in the O-arm group were repositioned intraoperatively (p = 0.003). One patient in the iCT-Airo group and 2 in the O-arm group experienced postoperative neurological deficits related to hardware malposition. The mean surgical times in both groups were similar (276 [iCT-Airo] and 279 [O-arm] minutes). The mean exposure to radiation in the iCT-Airo group was significantly lower than that in the O-arm group (15.82 vs 19.12 mSv, respectively; p = 0.02).

CONCLUSIONS Introduction of a mobile CT scanner reduced the rate of screw repositioning, which enhanced patient safety and diminished radiation exposure for patients, but it did not improve overall accuracy compared to that of a mobile 3D platform.

 

Head-up display may facilitate safe keyhole surgery for cerebral aneurysm clipping

J Neurosurg 129:883–889, 2018

The head-up display (HUD) is a modern technology that projects images or numeric information directly into the observer’s sight line. Surgeons will no longer need to look away from the surgical view using the HUD system to confirm the preoperative or navigation image. The present study investigated the usefulness of the HUD system for performing cerebral aneurysm clipping surgeries.

METHODS Thirty-five patients underwent clipping surgery, including 20 keyhole surgeries for unruptured cerebral aneurysm, using the HUD system. Image information of structures such as the skull, cerebral vasculature, and aneurysm was integrated by the navigation software and linked with the positional coordinates of the microscope field of view. “Image injection” allowed visualization of the main structures that were concurrently tracked by the navigation image, and “closed shutter” switched the microscope field of view and the pointer image of the 3D brain image.

RESULTS The HUD system was effective for estimating the location and 3D anatomy of the aneurysm before craniotomy or dural opening in most patients. Scheduled keyhole minicraniotomy and opening of the sylvian fissure or partial rectal gyrus resection were performed on the optimized location with a minimum size in 20 patients.

CONCLUSIONS The HUD images superimposed on the microscope field of view were remarkably useful for less invasive and more safe aneurysm clipping and, in particular, keyhole clipping.

 

Ultrasonographic features of focal cortical dysplasia and their relevance for epilepsy surgery

Neurosurg Focus 45 (3):E5, 2018

Surgery has proven to be the best therapeutic option for drug-refractory cases of focal cortical dysplasia (FCD)–associated epilepsy. Seizure outcome primarily depends on the completeness of resection, rendering the intraoperative FCD identification and delineation particularly important. This study aims to assess the diagnostic yield of intraoperative ultrasound (IOUS) in surgery for FCD-associated drug-refractory epilepsy.

METHODS The authors prospectively enrolled 15 consecutive patients with drug-refractory epilepsy who underwent an IOUS-assisted microsurgical resection of a radiologically suspected FCD between January 2013 and July 2016. The findings of IOUS were compared with those of presurgical MRI postprocessing and the sonographic characteristics were analyzed in relation to the histopathological findings. The authors investigated the added value of IOUS in achieving completeness of resection and improving postsurgical seizure outcome.

RESULTS The neurosurgeon was able to identify the dysplastic tissue by IOUS in all cases. The visualization of FCD type I was more challenging compared to FCD II and the demarcation of its borders was less clear. Postsurgical MRI showed residual dysplasia in 2 of the 3 patients with FCD type I. In all FCD type II cases, IOUS allowed for a clear intraoperative visualization and demarcation, strongly correlating with presurgical MRI postprocessing. Postsurgical MRI confirmed complete resection in all FCD type II cases. Sonographic features correlated with the histopathological classification of dysplasia (sonographic abnormalities increase continuously in the following order: FCD IA/IB, FCD IC, FCD IIA, FCD IIB). In 1 patient with IOUS features atypical for FCD, histopathological investigation showed nonspecific gliosis.

CONCLUSIONS Morphological features of FCD, as identified by IOUS, correlate well with advanced presurgical imaging. The resolution of IOUS was superior to MRI in all FCD types. The appreciation of distinct sonographic features on IOUS allows the intraoperative differentiation between FCD and non-FCD lesions as well as the discrimination of different histological subtypes of FCD. Sonographic demarcation depends on the underlying degree of dysplasia. IOUS allows for more tailored resections by facilitating the delineation of the dysplastic tissue.

Intraoperative computed tomography as reliable navigation registration device in 200 cranial procedures

Acta Neurochirurgica (2018) 160:1681–1689

Registration accuracy is a main factor influencing overall navigation accuracy. Standard fiducial- or landmark-based patient registration is user dependent and error-prone. Intraoperative imaging offers the possibility for user-independent patient registration. The aim of this paper is to evaluate our initial experience applying intraoperative computed tomography (CT) for navigation registration in cranial neurosurgery, with a special focus on registration accuracy and effective radiation dose.

Methods A total of 200 patients (141 craniotomy, 19 transsphenoidal, and 40 stereotactic burr hole procedures) were investigated by intraoperative Craneotomía applying a 32-slice movable CTscanner, which was used for automatic navigation registration. Registration accuracy was measured by at least three skin fiducials that were not part of the registration process.

Results Automatic registration resulted in high registration accuracy (mean registration error: 0.93 ± 0.41 mm). Implementation of low-dose scanning protocols did not impede registration accuracy (registration error applying the full dose head protocol: 0.87 ± 0.36mmvs. the low dose sinus protocol 0.72 ± 0.43mm) while a reduction of the effective radiation dose by a factor of 8 could be achieved (mean effective radiation dose head protocol: 2.73 mSv vs. sinus protocol: 0.34 mSv).

Conclusion Intraoperative CT allows highly reliable navigation registration with low radiation exposure.

Cerebrovascular Imaging: Which Test is Best?

Neurosurgery 83:5–18, 2018

Optimal diagnosis and characterization of cerebrovascular disease requires selection of the appropriate imaging exam for each clinical situation.

In this review,we focus on intracranial arterial disease and discuss the techniques in current clinical use for imaging the blood vessel lumen and blood vessel wall, and for mapping cerebral hemodynamic impairment at the tissue level.

We then discuss specific strategies for imaging intracranial aneurysms, arteriovenous malformations, dural arterial venous fistulas, and arterial steno-occlusive disease.

Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection

J Neurosurg 128:1690–1697, 2018

The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination.

METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620–640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis.

RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery.

CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional bluelight excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov)

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.

Navigated 3D–ultrasound versus conventional neuronavigation during awake resections of eloquent low-grade gliomas

Acta Neurochir (2018) 160:331–342

The data showing usefulness of navigated 3D– ultrasound (3DUS) during awake resections of eloquent gliomas are sparse. Results of surgeries performed using 3DUS were never compared to procedures guided by standard neuronavigation. The aim of this work is to assess the effectiveness of 3DUS during awake resections of eloquent low-grade gliomas (LGGs) by comparing surgical results of two series of patients operated on using conventional neuronavigation and using 3DUS. To our knowledge, a similar study is lacking in the literature.

Methods During a 4-year period (September 2006 to August 2010) 21 awake resections of LGGs guided by neuronavigation (series 1, S1) were consecutively performed in Department of Neurosurgery in Bratislava. During another 4-year period (August 2010 to July 2014) 28 awake resections of LGGs guided by 3DUS (series 2, S2) were consecutively conducted. In both patients series, the eloquent cortical and subcortical structures were intraoperatively detected by direct electrical stimulation. Extent of tumor resection (EOR) and functional outcome in both series were compared.

Results EOR was significantly greater (p = 0.022) in S2 (median = 93.25%; mean = 86.79%), as compared to S1 (median 87.1%; mean = 75.85%). One permanent minor deficit in S1 and 2 minor deficits in S2 occurred, the difference was not significant (p = 0.999).

Conclusions Our work represents the first study comparing results of surgeries guided by 3DUS versus conventional navigation. The extent of awake resections of eloquent LGG guided by 3DUS was greater comparing to awake resections guided by standard neuronavigation; use of 3DUS had no impact on the number of new permanent deficits.

Investigation of the usefulness of fluorescein sodium fluorescence in stereotactic brain biopsy

Acta Neurochirurgica (2018) 160:317–324

Intraoperative frozen section assessment, to confirm acquisition of pathological tissues, is used in stereotactic brain biopsy to minimise sampling errors. Limitations include the dependence on dedicated neuro-oncology pathologists and an increase in operative duration. We investigated the use of intraoperative fluorescein sodium, and compared it to frozen section assessment, for confirming pathological tissue samples in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions.

Methods This prospective observational study consisted of 18 consecutive patients (12 men; median age, 63 years) who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. Twenty-three specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Positive and negative predictive values were calculated based on the fluorescence status of the biopsy samples with its corresponding intraoperative frozen section and definitive histopathological diagnosis.

Results Nineteen specimens (83%) were fluorescent and four (17%) were non-fluorescent. All 19 fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment and were suitable for histopathological diagnosis. Three of the non-fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment. One non-fluorescent specimen was non-diagnostic on frozen section and histological assessments. The positive predictive value was 100% and the negative predictive value was 25%.

Conclusions Fluorescein sodium fluorescence is as accurate as frozen section assessment in confirming sampling of pathological tissue in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. Fluorescein sodium fluorescence-guided stereotactic biopsy is a useful addition to the neurosurgical armamentarium.