Publications by authors named "Evgenii Belykh"

93 Publications

Novel System of Simulation Models for Aneurysm Clipping Training: Description of Models and Assessment of Face, Content, and Construct Validity.

Oper Neurosurg (Hagerstown) 2021 Oct 18. Epub 2021 Oct 18.

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.

Background: Aneurysm clipping simulation models are needed to provide tactile feedback of biological vessels in a nonhazardous but surgically relevant environment.

Objective: To describe a novel system of simulation models for aneurysm clipping training and assess its validity.

Methods: Craniotomy models were fabricated to mimic actual tissues and movement restrictions experienced during actual surgery. Turkey wing vessels were used to create aneurysm models with patient-specific geometry. Three simulation models (middle cerebral artery aneurysm clipping via a pterional approach, anterior cerebral artery aneurysm clipping via an interhemispheric approach, and basilar artery aneurysm clipping via an orbitozygomatic pretemporal approach) were subjected to face, content, and construct validity assessments by experienced neurosurgeons (n = 8) and neurosurgery trainees (n = 8).

Results: Most participants scored the model as replicating actual aneurysm clipping well and scored the difficulty of clipping as being comparable to that of real surgery, confirming face validity. Most participants responded that the model could improve clip-applier-handling skills when working with patients, which confirms content validity. Experienced neurosurgeons performed significantly better than trainees on all 3 models based on subjective (P = .003) and objective (P < .01) ratings and on time to complete the task (P = .04), which confirms construct validity. Simulations were used to discuss clip application strategies and compare them to prototype clinical cases.

Conclusion: This novel aneurysm clipping model can be used safely outside the wet laboratory; it has high face, content, and construct validity; and it can be an effective training tool for microneurosurgery training during aneurysm surgery courses.
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http://dx.doi.org/10.1093/ons/opab357DOI Listing
October 2021

Redosing of Fluorescein Sodium Improves Image Interpretation During Intraoperative Confocal Laser Endomicroscopy of Brain Tumors.

Front Oncol 2021 30;11:668661. Epub 2021 Sep 30.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States.

Background: Fluorescein sodium (FNa) is a fluorescence agent used with a wide-field operating microscope for intraoperative guidance and with confocal laser endomicroscopy (CLE) to evaluate brain tissue. Susceptibility of FNa to degradation over time may affect CLE image quality during prolonged surgeries. This study describes improved characteristics of CLE images after intraoperative redosing with FNa.

Methods: A retrospective analysis was performed using CLE images obtained from samples obtained during tumor resections with FNa-based fluorescence guidance with a wide-field operating microscope. The comparison groups included CLE images acquired after FNa redosing (redose imaging group), images from the same patients acquired after the initial FNa dose (initial-dose imaging group), and images from patients in whom redosing was not used (single-dose imaging group). A detailed assessment of image quality and interpretation regarding different FNa dosage and timing of imaging after FNa administration was conducted for all comparison groups.

Results: The brightest and most contrasting images were observed in the redose group compared to the initial-dose and single-dose groups (P<0.001). The decay of FNa signal negatively correlated with brightness (rho = -0.52, P<0.001) and contrast (rho = -0.57, P<0.001). Different doses of FNa did not significantly affect the brightness (P=0.15) or contrast (P=0.09) in CLE images. As the mean timing of imaging increased, the percentage of accurately diagnosed images decreased (P=0.03).

Conclusions: The decay of the FNa signal is directly associated with image brightness and contrast. The qualitative interpretation scores of images were highest for the FNa redose imaging group. Redosing with FNa to improve the utility of CLE imaging should be considered a safe and beneficial strategy during prolonged surgeries.
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http://dx.doi.org/10.3389/fonc.2021.668661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514872PMC
September 2021

Needle Parking Interrupted Suturing Technique for Microvascular Anastomosis: A Technical Note.

Oper Neurosurg (Hagerstown) 2021 Oct;21(5):E414-E420

Department of Neurosurgery, University of Fukui, Fukui, Japan.

Background: Interrupted and continuous suturing are 2 common techniques for microvascular anastomosis in cerebrovascular surgery. One of the technical complexities of interrupted suturing includes the risk of losing the needle in between interrupted sutures during knot tying, which may result in unnecessary movements and wasted time.

Objective: To report a new needle parking technique for microvascular anastomosis that addresses a needle control problem during interrupted suturing.

Methods: The needle parking technique involves puncturing both vessel walls at the site of the next provisional suture and leaving the needle parked in place while the knots at the first suture are being made. The thread is then cut, the needle is pulled through, and the process is repeated. Illustrative cases in which the needle parking technique was used are presented. We also compared time of anastomosis completion between the conventional interrupted, needle parking interrupted, and continuous suturing techniques during an in vitro study on standardized artificial vessels.

Results: This technique is being used successfully by the senior author for various cerebrovascular bypass surgeries. The in vitro study demonstrated that the needle parking technique can be significantly faster than the conventional interrupted suturing technique and may be as fast as continuous suturing.

Conclusion: Needle parking technique is a modification of conventional interrupted suturing and solves the problem of losing the needle during knot tying. This technique is simple, prevents unnecessary movements, and may result in a faster anastomosis time.
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http://dx.doi.org/10.1093/ons/opab280DOI Listing
October 2021

High-Dose Fluorescein Reveals Unusual Confocal Endomicroscope Imaging of Low-Grade Glioma.

Front Neurol 2021 16;12:668656. Epub 2021 Jul 16.

Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute, Phoenix, AZ, United States.

Fluorescence-guided brain tumor surgery using fluorescein sodium (FNa) for contrast is effective in high-grade gliomas. However, the effectiveness of this technique for visualizing noncontrast-enhancing and low-grade gliomas is unknown. This report is the first documented case of the concurrent use of wide-field fluorescence-guided surgery and confocal laser endomicroscopy (CLE) with high-dose FNa (40 mg/kg) for intraoperative visualization of tumor tissue cellularity in a nonenhancing glioma. A patient underwent fluorescence-guided surgery for a left frontal lobe mass without contrast enhancement on magnetic resonance imaging. The patient received 40 mg/kg FNa intravenously at the induction of anesthesia. Surgery was performed under visualization with a Yellow 560 filter and white-light wide-field imaging. Intraoperative CLE produced high-quality images of the lesion 1.5 h after FNa injection. Frozen-section analysis demonstrated findings comparable to those of intraoperative CLE visualization and consistent with World Health Organization (WHO) glioma grades II-III. The patient recovered without complications. Analysis of the permanent histologic sections identified the tumor as an anaplastic oligodendroglioma, IDH-mutant, 1p/19q co-deleted, consistent with WHO grade III because of discrete foci of hypercellularity and increased mitotic figures, but large regions of the lesion were low grade. The use of high-dose FNa in this patient with a nonenhancing borderline low-grade/high-grade glioma produced actionable wide-field fluorescence imaging using the operating microscope and improved CLE visualization of tumor cellularity. Higher doses of FNa for intraoperative CLE imaging and possible simultaneous wide-field fluorescence surgical guidance in nonenhancing gliomas merit further investigation.
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http://dx.doi.org/10.3389/fneur.2021.668656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322731PMC
July 2021

Partial Gyrus Rectus Resection as a Technique to Improve the Exposure to the Anterior Communicating Artery Complex through the Junctional Triangle: A Quantitative Study.

J Neurol Surg B Skull Base 2021 Jul 5;82(Suppl 3):e211-e216. Epub 2020 May 5.

Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States.

 The junctional triangle, formed by the distal A1 anterior cerebral artery (ACA) segment, the proximal A2 ACA segment, and the medial surface of gyrus rectus (GR), is a corridor of access to superiorly and posteriorly projecting anterior communicating artery (AComA) aneurysms that is widened by GR retraction or resection. Exposure of the AComA complex through the junctional triangle after GR resection has not been previously quantitatively evaluated.  GR resection extent and increase in artery exposure through the junctional triangle were assessed in this study.  This study was conducted in the laboratory with a pterional approach, exposing the AComA complex.  Ten sides of five cadaveric heads were considered.  Exposure extent of ipsilateral and contralateral A1, A2, and AComA and accessibility of branches coming off the AComA complex were measured before and after GR resection. The GR was resected until sufficient bilateral A2 and contralateral A1 exposures were achieved. GR resection span was measured.  The mean (standard deviation) resected span of GR was 7 ± 3.9 mm. After GR resection, the exposed span of the ipsilateral A2 increased from 2 ± 0.7 mm to 4 ± 1.1 mm (  = 0.001); contralateral A2 exposure increased from 3 ± 1.5 mm to 4 ± 1.1 mm (  = 0.03). Contralateral recurrent artery of Heubner (RAH) and orbitofrontal artery were accessible in five and eight specimens, respectively, before GR resection and in all 10 after resection.  GR resection improves exposure of bilateral A2 segments through the junctional triangle. Exposure improvement is greater for the ipsilateral A2 than contralateral A2. The junctional triangle concept is enhanced by partial GR resection during surgery for superior and posterior AComA aneurysms.
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http://dx.doi.org/10.1055/s-0040-1710517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289494PMC
July 2021

Editorial: Applications of Fluorescence in Surgery and Interventional Diagnostics.

Front Surg 2021 12;8:624124. Epub 2021 Apr 12.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States.

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http://dx.doi.org/10.3389/fsurg.2021.624124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074625PMC
April 2021

Proposed definition of competencies for surgical neuro-oncology training.

J Neurooncol 2021 May 21;153(1):121-131. Epub 2021 Apr 21.

Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.

Objective: The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established.

Methods: We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology.

Result: In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families.

Conclusions And Relevance: The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.
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http://dx.doi.org/10.1007/s11060-021-03750-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131302PMC
May 2021

Supracerebellar infratentorial inverted subchoroidal approach to lateral ventricle lesions: Anatomical study and illustrative case.

Surg Neurol Int 2021 3;12:39. Epub 2021 Feb 3.

Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, United States.

Background: This study provides an anatomical description of a novel supracerebellar infratentorial inverted subchoroidal (SIIS) approach to the lateral ventricle. An illustrative case is presented in which this approach was used to simultaneously resect two tumors residing in the posterior fossa and lateral ventricle.

Methods: The SIIS approach was performed on five cadaveric heads using microsurgical and endoscopic techniques. Target points were defined in the lateral ventricle, and quantitative analysis was performed to assess limits of exposure within the lateral ventricle. Two coronal reference planes corresponding to the anterior and posterior margins of the lateral ventricle body were defined. Distances from target points to reference planes were measured, and an imaging-based predicting system was provided according to obtained measurements to guide preoperative approach selection.

Results: Mean (standard deviation) distances between the predefined target points indicating the anterior limits and the anterior plane were 9 (7.0) mm, 11 (5.8) mm, and 7 (5.1) mm; posterior limits had distances of 8 (3.0) mm, 17 (9.2) mm, 15 (9.2) mm, and 9 (7.2) mm to the posterior plane. Limiting factors of the choroidal fissure dissection were the venous angle anteriorly and thalamocaudate vein posteriorly. The position of the venous angle had a high negative correlation with the anterior exposure limit ( = -0.87, < 0.001; = -0.92, < 0.001).

Conclusion: A step-by-step anatomical description of a new SIIS approach is given, and a quantitative description of the limits of the exposure is provided to evaluate the application of this approach.
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http://dx.doi.org/10.25259/SNI_909_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881503PMC
February 2021

From Krönlein, through madness, to a useful modern surgery: the journey of the transorbital corridor to enter the neurosurgical armamentarium.

J Neurosurg 2021 Feb 5:1-10. Epub 2021 Feb 5.

1The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and.

Transorbital surgery has gained recent notoriety because of its incorporation into endoscopic skull base surgery. The use of this surgical corridor has been pervasive throughout the 20th century. It has been utilized by multiple disciplines for both clinical and experimental purposes, although its historical origin is medically and ethically controversial. Hermann Knapp first introduced the orbital surgical technique in 1874, and Rudolf Krönlein introduced his procedure in 1889. Rivalry between Walter Dandy in neurosurgery and Raynold Berke in ophthalmology further influenced methods of tackling intracranial and intraorbital pathologies. In 1946, Walter Freeman revolutionized psychosurgery by completing seemingly successful transorbital leucotomies and promoting their minimally invasive and benign surgical characteristics. However, as Freeman's legacy came into disrepute, so did the transorbital brain access corridor, again resulting in its stunted evolution. Microsurgery and endoscopy further influenced the use, or lack thereof, of the transorbital corridor in neurosurgical approaches. Historical analysis of present goals in modern skull base surgery echoes the principles established through an approach described almost 150 years ago: minimal invasion, minimal morbidity, and priority of patient satisfaction. The progression of the transorbital approach not only reflects psychosocial influences on medical therapy, as well as the competition of surgical pioneers for supremacy, but also describes the diversification of skull base techniques, the impact of microsurgical mastery on circumferential neurosurgical corridors, the influence of technology on modernizing skull base surgery, and the advancing trend of multidisciplinary surgical excellence.
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http://dx.doi.org/10.3171/2020.8.JNS201251DOI Listing
February 2021

Molecular Imaging of Glucose Metabolism for Intraoperative Fluorescence Guidance During Glioma Surgery.

Mol Imaging Biol 2021 08 5;23(4):586-596. Epub 2021 Feb 5.

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.

Purpose: This study evaluated the use of molecular imaging of fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as a discriminatory marker for intraoperative tumor border identification in a murine glioma model.

Procedures: 2-NBDG was assessed in GL261 and U251 orthotopic tumor-bearing mice. Intraoperative fluorescence of topical and intravenous 2-NBDG in normal and tumor regions was assessed with an operating microscope, handheld confocal laser scanning endomicroscope (CLE), and benchtop confocal laser scanning microscope (LSM). Additionally, 2-NBDG fluorescence in tumors was compared with 5-aminolevulinic acid-induced protoporphyrin IX fluorescence.

Results: Intravenously administered 2-NBDG was detectable in brain tumor and absent in contralateral normal brain parenchyma on wide-field operating microscope imaging. Intraoperative and benchtop CLE showed preferential 2-NBDG accumulation in the cytoplasm of glioma cells (mean [SD] tumor-to-background ratio of 2.76 [0.43]). Topically administered 2-NBDG did not create sufficient tumor-background contrast for wide-field operating microscope imaging or under benchtop LSM (mean [SD] tumor-to-background ratio 1.42 [0.72]). However, topical 2-NBDG did create sufficient contrast to evaluate cellular tissue architecture and differentiate tumor cells from normal brain parenchyma. Protoporphyrin IX imaging resulted in a more specific delineation of gross tumor margins than intravenous or topical 2-NBDG and a significantly higher tumor-to-normal-brain fluorescence intensity ratio.

Conclusion: After intravenous administration, 2-NBDG selectively accumulated in the experimental brain tumors and provided bright contrast under wide-field fluorescence imaging with a clinical-grade operating microscope. Topical 2-NBDG was able to create a sufficient contrast to differentiate tumor from normal brain cells on the basis of visualization of cellular architecture with CLE. 5-Aminolevulinic acid demonstrated superior specificity in outlining tumor margins and significantly higher tumor background contrast. Given the nontoxicity of 2-NBDG, its use as a topical molecular marker for noninvasive in vivo intraoperative microscopy is encouraging and warrants further clinical evaluation.
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http://dx.doi.org/10.1007/s11307-021-01579-zDOI Listing
August 2021

Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy.

Microcirculation 2021 04 8;28(3):e12678. Epub 2021 Feb 8.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.

Objective: Qualitative and quantitative analyses of blood flow in normal and pathologic brain and spinal cord microvasculature were performed using confocal laser endomicroscopy (CLE).

Methods: Blood flow in cortical, dural, and spinal cord microvasculature was assessed in vivo in swine. We assessed microvasculature under normal conditions and after vessel occlusion, brain injury due to cold or surgical trauma, and cardiac arrest. Tumor-associated microvasculature was assessed in vivo and ex vivo in 20 patients with gliomas.

Results: We observed erythrocyte flow in vessels 5-500 µm in diameter. Thrombosis, flow arrest and redistribution, flow velocity changes, agglutination, and cells rolling were assessed in normal and injured brain tissue. Microvasculature in in vivo CLE images of gliomas was classified as normal in 68% and abnormal in 32% of vessels on the basis of morphological appearance. Dural lymphatic channels were discriminated from blood vessels. Microvasculature CLE imaging was possible for up to 30 minutes after a 1 mg/kg intravenous dose of fluorescein.

Conclusions: CLE imaging allows assessment of cerebral and tumor microvasculature and blood flow alterations with subcellular resolution intraoperative imaging demonstrating precise details of real-time cell movements. Research and clinical scenarios may benefit from this novel intraoperative in vivo microscopic fluorescence imaging modality.
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http://dx.doi.org/10.1111/micc.12678DOI Listing
April 2021

The Neuroanatomic Studies of Albert L. Rhoton Jr. in Historical Context: An Analysis of Origin, Evolution, and Application.

World Neurosurg 2021 07 30;151:258-276. Epub 2020 Dec 30.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona. Electronic address:

The incorporation of perspective into art and science revolutionized the study of the brain. Beginning in about 1504, Leonardo da Vinci began to model the ventricles of the brain in three dimensions. A few years later, Andreus Vesalius illustrated radically novel brain dissections. Thomas Willis' work, Cerebri Anatome (1664), illustrated by Christopher Wren, remarkably showed the brain undersurface. Later, in the early 1800s, Charles Bell's accurate images of neural structures changed surgery. In the 1960s, Albert L. Rhoton Jr. (1932-2016) began to earn his place among the preeminent neuroanatomists by focusing his lens on microanatomy to harness a knowledge of microneurosurgery, master microneurologic anatomy, and use it to improve the care of his patients. Although his biography and works are well known, no analysis has been conducted to identify the progression, impact, and trends in the totality of his publications, and no study has assessed his work in a historical context compared with the contributions of other celebrated anatomists. We analyzed 414 of 508 works authored by Rhoton; these studies were analyzed according to subjects discussed, including anatomic region, surgical approaches, subjects covered, anatomic methods used, forms of multimedia, and subspecialty. Rhoton taught detailed neuroanatomy from a surgical perspective using meticulous techniques that evolved as the technical demands of neurosurgery advanced, inspiring students and contemporaries. His work aligns him with renowned figures in neuroanatomy, arguably establishing him historically as the most influential anatomist of the neurosurgical era.
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http://dx.doi.org/10.1016/j.wneu.2020.12.101DOI Listing
July 2021

The Glossopharyngo-Cochlear Triangle-Part I: Quantitative Anatomic Analysis of High-Riding Posterior Inferior Cerebellar Artery Aneurysms Exposed Through the Extended Retrosigmoid Approach.

Oper Neurosurg (Hagerstown) 2021 02;20(3):242-251

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.

Background: An extended retrosigmoid approach can offer sufficient space for clip reconstruction of some high-riding posterior inferior cerebellar artery (PICA) aneurysms.

Objective: To quantitatively investigate the glossopharyngo-cochlear triangle (GCT) and anatomic structures within it.

Methods: Extended retrosigmoid craniotomies were performed on 10 sides of cadaveric heads, and the GCT was identified in each specimen. The length of the base and the area of the GCT were measured. The depth of the vertebrobasilar system and the abducens nerve to the GCT were measured. The proximal and distal exposable and controllable points on the vertebrobasilar system were identified. Two imaging-based patient selection algorithms are provided using the lengths from those points to the vertebral artery dural entry point and the superoinferior distances from those points to the inferior edge of the foramen magnum. Other factors related to accessibility via the GCT were investigated.

Results: The mean (standard deviation [SD]) area of the GCT was 45.7 (12.55) mm2. The mean (SD) depth of the abducens nerve was 14.3 (1.42) mm. The mean (SD) superoinferior distances from the foramen magnum to those points were 23.1 (7.39), 24.7 (8.25), 30.0 (9.56), and 32.6 (7.79) mm, respectively. The lower segment of the vertebrobasilar system was more superficial in the setting of a high-lying vertebrobasilar junction (VBJ) than a low-lying VBJ.

Conclusion: We describe the GCT in an extended retrosigmoid approach for high-riding PICA aneurysms and evaluate the spatial relationship of the neurovascular structures within it. Two potential algorithms are offered for preoperative patient selection.
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http://dx.doi.org/10.1093/ons/opaa356DOI Listing
February 2021

Intraoperative Confocal Laser Endomicroscopy Examination of Tissue Microstructure During Fluorescence-Guided Brain Tumor Surgery.

Front Oncol 2020 4;10:599250. Epub 2020 Dec 4.

Department of Neurosurgery, The Loyal and Edith Davis Neurosurgical Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States.

Background: Noninvasive intraoperative optical biopsy that provides real-time imaging of histoarchitectural (cell resolution) features of brain tumors, especially at the margin of invasive tumors, would be of great value. To assess clinical-grade confocal laser endomicroscopy (CLE) and to prepare for its use intraoperatively , we performed an assessment of CLE imaging in brain lesions.

Methods: Tissue samples from patients who underwent intracranial surgeries with fluorescein sodium (FNa)-based wide-field fluorescence guidance were acquired for immediate intraoperative optical biopsies with CLE. Hematoxylin-eosin-stained frozen section analysis of the same specimens served as the gold standard for blinded neuropathology comparison. FNa 2 to 5 mg/kg was administered upon induction of anesthesia, and FNa 5 mg/kg was injected for CLE contrast improvement. Histologic features were identified, and the diagnostic accuracy of CLE was assessed.

Results: Of 77 eligible patients, 47 patients with 122 biopsies were enrolled, including 32 patients with gliomas and 15 patients with other intracranial lesions. The positive predictive value of CLE optical biopsies was 97% for all specimens and 98% for gliomas. The specificity of CLE was 90% for all specimens and 94% for gliomas. The second FNa injection in seven patients, a mean of 2.6 h after the first injection, improved image quality and increased the percentage of accurately diagnosed images from 67% to 93%. Diagnostic CLE features of lesional glioma biopsies and normal brain were identified. Seventeen histologic features were identified.

Conclusions: Results demonstrated high specificity and positive predictive value of intraoperative CLE optical biopsies and justify an intraoperative trial. This new portable, noninvasive intraoperative imaging technique provides diagnostic features to discriminate lesional tissue with high specificity and is feasible for incorporation into the fluorescence-guided surgery workflow, particularly for patients with invasive brain tumors.
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http://dx.doi.org/10.3389/fonc.2020.599250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746822PMC
December 2020

Confocal Laser Endomicroscopy Assessment of Pituitary Tumor Microstructure: A Feasibility Study.

J Clin Med 2020 Sep 29;9(10). Epub 2020 Sep 29.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.

This is the first study to assess confocal laser endomicroscopy (CLE) use within the transsphenoidal approach and show the feasibility of obtaining digital diagnostic biopsies of pituitary tumor tissue after intravenous fluorescein injection. We confirmed that the CLE probe reaches the tuberculum sellae through the transnasal transsphenoidal corridor in cadaveric heads. Next, we confirmed that CLE provides images with identifiable histological features of pituitary adenoma. Biopsies from nine patients who underwent pituitary adenoma surgery were imaged ex vivo at various times after fluorescein injection and were assessed by a blinded board-certified neuropathologist. With frozen sections used as the standard, pituitary adenoma was diagnosed as "definitively" for 13 and as "favoring" in 3 of 16 specimens. CLE digital biopsies were diagnostic for pituitary adenoma in 10 of 16 specimens. The reasons for nondiagnostic CLE images were biopsy acquisition <1 min or >10 min after fluorescein injection ( = 5) and blood artifacts ( = 1). In conclusion, fluorescein provided sufficient contrast for CLE at a dose of 2 mg/kg, optimally 1-10 min after injection. These results provide a basis for further in vivo studies using CLE in transsphenoidal surgery.
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http://dx.doi.org/10.3390/jcm9103146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600847PMC
September 2020

Tailoring the surgical corridor to the basilar apex in the pretemporal transcavernous approach: morphometric analyses of different neurovascular mobilization maneuvers.

Acta Neurochir (Wien) 2020 11 5;162(11):2731-2741. Epub 2020 Aug 5.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 W. Thomas Rd, Phoenix, AZ, 85013, USA.

Background: The pretemporal transcavernous approach (PTA) provides optimal exposure and access to the basilar artery (BA); however, the PTA can be invasive when vital neurovascular structures are mobilized. The goal of this study was to evaluate mobilization strategies to tailor approaches to the BA.

Methods: After an orbitozygomatic craniotomy, 10 sides of 5 cadaveric heads were used to assess the surgical access to the BA via the opticocarotid triangle (OCT), carotid-oculomotor triangle (COT), and oculomotor-tentorial triangle (OTT). Measurements were obtained, and morphometric analyses were performed for natural neurovascular positions and after each stepwise expansion maneuver. An imaginary line connecting the midpoints of the limbus sphenoidale and dorsum sellae was used as a reference to normalize the measurements of BA exposure and to facilitate the clinical applicability of this technique.

Results: In the OCT, the exposed BA segment ranged from - 1 ± 3.9 to + 6 ± 2.0 mm in length in its natural position. In the COT, the accessible BA segment ranged from - 4 ± 2.3 to - 2 ± 3.0 mm in length in its natural position. Via the OTT, the accessible BA segment ranged from - 7 ± 2.6 to - 5 ± 2.8 mm in length in its natural position. In the OCT, COT, and OTT, a posterior clinoidectomy extended the exposure down to - 6 ± 2.7, - 8 ± 2.5, and - 9 ± 2.9 mm, respectively.

Conclusions: This study quantitatively evaluated the need for the expansion maneuvers in the PTA to reach BA aneurysms according to the patient's anatomical characteristics.
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http://dx.doi.org/10.1007/s00701-020-04490-8DOI Listing
November 2020

Provision of rapid and specific ex vivo diagnosis of central nervous system lymphoma from rodent xenograft biopsies by a fluorescent aptamer.

J Neurosurg 2020 Jul 24:1-8. Epub 2020 Jul 24.

Departments of1Neurosurgery.

Objective: Differentiating central nervous system (CNS) lymphoma from other intracranial malignancies remains a clinical challenge in surgical neuro-oncology. Advances in clinical fluorescence imaging contrast agents and devices may mitigate this challenge. Aptamers are a class of nanomolecules engineered to bind cellular targets with antibody-like specificity in a fraction of the staining time. Here, the authors determine if immediate ex vivo fluorescence imaging with a lymphoma-specific aptamer can rapidly and specifically diagnose xenografted orthotopic human CNS lymphoma at the time of biopsy.

Methods: The authors synthesized a fluorescent CNS lymphoma-specific aptamer by conjugating a lymphoma-specific aptamer with Alexa Fluor 488 (TD05-488). They modified human U251 glioma cells and Ramos lymphoma cells with a lentivirus for constitutive expression of red fluorescent protein and implanted them intracranially into athymic nude mice. Three to 4 weeks postimplantation, acute slices (biopsies, n = 28) from the xenografts were collected, placed in aptamer solution, and imaged with a Zeiss fluorescence microscope. Three aptamer staining concentrations (0.3, 1.0, and 3.0 μM) and three staining times (5, 10, and 20 minutes) followed by a 1-minute wash were tested. A file of randomly selected images was distributed to neurosurgeons and neuropathologists, and their ability to distinguish CNS lymphoma from negative controls was assessed.

Results: The three staining times and concentrations of TD05-488 were tested to determine the diagnostic accuracy of CNS lymphoma within a frozen section time frame. An 11-minute staining protocol with 1.0-μM TD05-488 was most efficient, labeling 77% of positive control lymphoma cells and less than 1% of negative control glioma cells (p < 0.001). This protocol permitted clinicians to positively identify all positive control lymphoma images without misdiagnosing negative control images from astrocytoma and normal brain.

Conclusions: Ex vivo fluorescence imaging is an emerging technique for generating rapid histopathological diagnoses. Ex vivo imaging with a novel aptamer-based fluorescent nanomolecule could provide an intraoperative tumor-specific diagnosis of CNS lymphoma within 11 minutes of biopsy. Neurosurgeons and neuropathologists interpreted images generated with this molecular probe with high sensitivity and specificity. Clinical application of TD05-488 may permit specific intraoperative diagnosis of CNS lymphoma in a fraction of the time required for antibody staining.
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http://dx.doi.org/10.3171/2020.4.JNS192476DOI Listing
July 2020

Letter to the Editor: Factors that Influence Quantification of Fluorescent Signal During the 5-ALA-Guided Surgery.

World Neurosurg 2020 07;139:700-702

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2020.04.078DOI Listing
July 2020

Blood-Brain Barrier, Blood-Brain Tumor Barrier, and Fluorescence-Guided Neurosurgical Oncology: Delivering Optical Labels to Brain Tumors.

Front Oncol 2020 5;10:739. Epub 2020 Jun 5.

Department of Neurosurgery, Neuroscience Center, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

Recent advances in maximum safe glioma resection have included the introduction of a host of visualization techniques to complement intraoperative white-light imaging of tumors. However, barriers to the effective use of these techniques within the central nervous system remain. In the healthy brain, the blood-brain barrier ensures the stability of the sensitive internal environment of the brain by protecting the active functions of the central nervous system and preventing the invasion of microorganisms and toxins. Brain tumors, however, often cause degradation and dysfunction of this barrier, resulting in a heterogeneous increase in vascular permeability throughout the tumor mass and outside it. Thus, the characteristics of both the blood-brain and blood-brain tumor barriers hinder the vascular delivery of a variety of therapeutic substances to brain tumors. Recent developments in fluorescent visualization of brain tumors offer improvements in the extent of maximal safe resection, but many of these fluorescent agents must reach the tumor via the vasculature. As a result, these fluorescence-guided resection techniques are often limited by the extent of vascular permeability in tumor regions and by the failure to stain the full volume of tumor tissue. In this review, we describe the structure and function of both the blood-brain and blood-brain tumor barriers in the context of the current state of fluorescence-guided imaging of brain tumors. We discuss features of currently used techniques for fluorescence-guided brain tumor resection, with an emphasis on their interactions with the blood-brain and blood-tumor barriers. Finally, we discuss a selection of novel preclinical techniques that have the potential to enhance the delivery of therapeutics to brain tumors in spite of the barrier properties of the brain.
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http://dx.doi.org/10.3389/fonc.2020.00739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290051PMC
June 2020

Contralateral interoptic approach to paraclinoid aneurysms: a patient-selection algorithm based on anatomical investigation and clinical validation.

J Neurosurg 2020 Jun 12:1-9. Epub 2020 Jun 12.

Objective: Aneurysms that arise on the medial surface of the paraclinoid segment of the internal carotid artery (ICA) are surgically challenging. The contralateral interoptic trajectory, which uses the space between the optic nerves, can partially expose the medial surface of the paraclinoid ICA. In this study, the authors quantitatively measure the area of the medial ICA accessible through the interoptic triangle and propose a potential patient-selection algorithm that is based on preoperative measurements on angiographic imaging.

Methods: The contralateral interoptic trajectory was studied on 10 sides of 5 cadaveric heads, through which the medial paraclinoid ICA was identified. The falciform ligament medial to the contralateral optic canal was incised, the contralateral optic nerve was gently elevated, and the medial surface of the paraclinoid ICA was inspected via different viewing angles to obtain maximal exposure. The accessible area on the carotid artery was outlined. The distance from the distal dural ring (DDR) to the proximal and distal borders of this accessible area was measured. The superior and inferior borders were measured using the clockface method relative to a vertical line on the coronal plane. To validate these parameters, preoperative measurements and intraoperative findings were reviewed in 8 clinical cases.

Results: In the sagittal plane, the mean (SD) distances from the DDR to the proximal and distal ends of the accessible area on the paraclinoid ICA were 2.5 (1.52) mm and 8.4 (2.32) mm, respectively. In the coronal plane, the mean (SD) angles of the superior and inferior ends of the accessible area relative to a vertical line were 21.7° (14.84°) and 130.9° (12.75°), respectively. Six (75%) of 8 clinical cases were consistent with the proposed patient-selection algorithm.

Conclusions: The contralateral interoptic approach is a feasible route to access aneurysms that arise from the medial paraclinoid ICA. An aneurysm can be safely clipped via the contralateral interoptic trajectory if 1) both proximal and distal borders of the aneurysm neck are 2.5-8.4 mm distal to the DDR, and 2) at least one border of the aneurysm neck on the coronal clockface is 21.7°-130.9° medial to the vertical line.
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http://dx.doi.org/10.3171/2020.3.JNS193205DOI Listing
June 2020

The endoscopic endonasal eustachian tube anterolateral mobilization strategy: minimizing the cost of the extreme-medial approach.

J Neurosurg 2020 Mar 13;134(3):831-842. Epub 2020 Mar 13.

1Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.

Objective: The ventral jugular foramen and the infrapetrous region are difficult to access through conventional lateral and posterolateral approaches. Endoscopic endonasal approaches to this region are obstructed by the eustachian tube (ET). This study presents a novel strategy for mobilizing the ET while preserving its integrity. Qualitative and quantitative comparisons with previous ET management paradigms are also presented.

Methods: Ten dry skulls were analyzed. Four ET management strategies were sequentially performed on a total of 6 sides of cadaveric head specimens. Four measurement groups were generated: in group A, the ET was intact and not mobilized; in group B, the ET was mobilized inferolaterally; in group C, the ET underwent anterolateral mobilization; and in group D, the ET was resected. ET range of mobilization, surgical exposure area, and surgical freedom were measured and compared among the groups.

Results: Wide exposure of the infrapetrous region and jugular foramen was achieved by removing the pterygoid process, unroofing the cartilaginous ET up to the level of the posterior aspect of the foramen ovale, and detaching the ET from the skull base and soft palate. Anterolateral mobilization of the ET facilitated significantly more retraction (a 126% increase) of the ET than inferolateral mobilization (mean ± SD: 20.8 ± 11.2 mm vs 9.2 ± 3.6 mm [p = 0.02]). Compared with group A, groups C and D had enhanced surgical exposure (142.5% [1176.9 ± 935.7 mm2] and 155.9% [1242.0 ± 1096.2 mm2], respectively, vs 485.4 ± 377.6 mm2 for group A [both p = 0.02]). Furthermore, group C had a significantly larger surgical exposure area than group B (p = 0.02). No statistically significant difference was found between the area of exposure obtained by ET removal and anterolateral mobilization. Anterolateral mobilization of the ET resulted in a 39.5% increase in surgical freedom toward the exocranial jugular foramen compared with that obtained through inferolateral mobilization of the ET (67.2° ± 20.5° vs 48.1° ± 6.7° [p = 0.047]) and a 65.4% increase compared with that afforded by an intact ET position (67.2° ± 20.5° vs 40.6° ± 14.3° [p = 0.03]).

Conclusions: Anterolateral mobilization of the ET provides excellent access to the ventral jugular foramen and infrapetrous region. The surgical exposure obtained is superior to that achieved with other ET management strategies and is comparable to that obtained by ET resection.
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http://dx.doi.org/10.3171/2019.12.JNS192285DOI Listing
March 2020

Using the Post-Descendens Hypoglossal Nerve in Hypoglossal-Facial Anastomosis: An Anatomic and Histologic Feasibility Study.

Oper Neurosurg (Hagerstown) 2020 09;19(4):436-443

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.

Background: Hypoglossal-facial anastomosis (HFA) is a popular facial reanimation technique. Mobilizing the intratemporal segment of the facial nerve and using the post-descendens hypoglossal nerve (ie, the segment distal to the take-off of descendens hypoglossi) have been proposed to improve results. However, no anatomic study has verified the feasibility of this technique.

Objective: To assess the anatomic feasibility of HFA and the structural compatibility between the 2 nerves when the intratemporal facial and post-descendens hypoglossal nerves are used.

Methods: The facial and hypoglossal nerves were exposed bilaterally in 10 sides of 5 cadaveric heads. The feasibility of a side-to-end (ie, partial end-to-end) HFA with partial sectioning of the post-descendens hypoglossal nerve and the mobilized intratemporal facial nerve was assessed. The axonal count and cross-sectional area of the facial and hypoglossal nerves at the point of anastomosis were assessed.

Results: The HFA was feasible in all specimens with a mean (standard deviation) 9.3 (5.5) mm of extra length on the facial nerve. The axonal counts and cross-sectional areas of the hypoglossal and facial nerves matched well. Considering the reduction in the facial nerve cross-sectional area after paralysis, the post-descendens hypoglossal nerve can provide adequate axonal count and area to accommodate the facial nerve stump.

Conclusion: Using the post-descendens hypoglossal nerve for side-to-end anastomosis with the mobilized intratemporal facial nerve is anatomically feasible and provides adequate axonal count for facial reanimation. When compared with use of the pre-descendens hypoglossal nerve, this technique preserves C1 fibers and has a potential to reduce glottic complications.
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http://dx.doi.org/10.1093/ons/opz408DOI Listing
September 2020

A Thoracic Surgeon Among Neurosurgeons: Edward Archibald's Forgotten Influence on the Professionalization of Neurosurgery.

World Neurosurg 2020 Apr 30;136:234-247. Epub 2019 Dec 30.

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA. Electronic address:

Edward Archibald, Professor of Surgery at McGill University (1904-1945), Montreal, Canada, was the foremost thoracic surgeon of his generation. Although instrumental in establishing the American Board of Surgery and in standardizing surgical training, he was also influential as a neurosurgeon. Archibald, an early member invited by Harvey Cushing to join the Society of Neurological Surgeons, helped establish neurosurgery as a distinct, specialized discipline. We review Archibald's contributions to the development of neurosurgery in light of his encyclopedic 1908 monograph, "Surgical Affections and Wounds of the Head," which we compare and contrast to the contemporary treatise by Cushing in the same year. Through his writings and correspondence with Wilder Penfield and Cushing, we also describe his role in the creation of the Montreal Neurological Institute. Primary archival sources addressing the professional relationship between Archibald and Cushing and between Archibald and Penfield were consulted. Archibald's personal acquaintance with the principal neurosurgeons of the day, his insight into their personalities, their prominence in the field, and their career paths played a critical role in influencing Penfield to consider relocating to Montreal from Columbia University, despite tempting offers from Boston and Philadelphia. However, it was Archibald's support and mentorship for the creation of an academic center that finally convinced Penfield to move to McGill University. As one of the most influential surgeons of the early 20th century and a founding figure of modern neurosurgery, Archibald is an important part of neurosurgery's legacy.
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http://dx.doi.org/10.1016/j.wneu.2019.12.136DOI Listing
April 2020

Applications of Microscope-Integrated Indocyanine Green Videoangiography in Cerebral Revascularization Procedures.

Front Surg 2019 28;6:59. Epub 2019 Nov 28.

Department of Neurosurgery, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute, Phoenix, AZ, United States.

Indocyanine green videoangiography (ICG-VA) is a near-infrared range fluorescent marker used for intraoperative real-time assessment of flow in cerebrovascular surgery. Given its high spatial and temporal resolution, ICG-VA has been widely established as a useful technique to perform a qualitative analysis of the graft patency during revascularization procedures. In addition, this fluorescent modality can also provide valuable qualitative and quantitative information regarding the cerebral blood flow within the bypass graft and in the territories supplied. Digital subtraction angiography (DSA) is considered to be the gold standard diagnostic modality for postoperative bypass graft patency assessment. However, this technique is time and labor intensive and an expensive interventional procedure. In contrast, ICG-VA can be performed intraoperatively with no significant addition to the total operative time and, when used correctly, can accurately show acute occlusion. Such time-sensitive ischemic injury detection is critical for flow reestablishment through direct surgical management. In addition, ICG has an excellent safety profile, with few adverse events reported in the literature. This review outlines the chemical behavior, technical aspects, and clinical implications of this tool as an intraoperative adjunct in revascularization procedures.
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http://dx.doi.org/10.3389/fsurg.2019.00059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902023PMC
November 2019

Comparative Analysis of Continuous Suturing, Interrupted Suturing, and Cyanoacrylate-Based Lid Techniques for End-to-End Microvascular Anastomosis: Laboratory Investigation.

World Neurosurg 2020 Feb 14;134:465-471. Epub 2019 Nov 14.

Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA. Electronic address:

Background: Mastery of the microsurgical anastomosis is an indispensable component of neurosurgical training. However, in many resource-limited countries, the training, materials, and equipment to obtain these surgical and decision making skills are severely lacking. This study aimed to compare different suturing techniques for microvascular anastomosis and to complete a comparative assessment of the performance of a young neurosurgeon when using the various techniques.

Methods: We compared 3 end-to-end suturing techniques for microvascular anastomosis: interrupted suturing, continuous suturing, and a 2-octyl-cyanoacrylate-based lid technique using an umbilical artery model. We assessed the subjective difficulty of the suturing technique, the time needed to perform the procedure, and the flow rate and leakage of the vessel after each technique. This study was designed to use materials that would be available in developing countries. Surgical apparatus used, such as operating microscopes, were first-generation technology, and testing procedures were designed for neurosurgical residents in developing countries.

Results: The mean times to complete the anastomosis were 20.7 ± 7.7 minutes for the interrupted technique, 26.4 ± 7.7 minutes for the continuous technique, and 12.5 ± 2.5 minutes for the lid technique; these values were significantly different (P < 0.01). The differences among the 3 techniques in leakage and flow rates and subjective difficulty in performance were not significant.

Conclusions: Suturing time was the only statistically significant difference among the 3 anastomotic techniques, with the lid technique apparently the quickest to perform. Such techniques can be designed to assess microsurgical abilities and help neurosurgery residents in developing countries improve their surgical skills and techniques.
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http://dx.doi.org/10.1016/j.wneu.2019.11.054DOI Listing
February 2020

Application of Fluorescein Fluorescence in Vascular Neurosurgery.

Front Surg 2019 18;6:52. Epub 2019 Sep 18.

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States.

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. 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. 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. 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.
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http://dx.doi.org/10.3389/fsurg.2019.00052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759993PMC
September 2019

Development of a Simulation Model for Fluorescence-Guided Brain Tumor Surgery.

Front Oncol 2019 16;9:748. Epub 2019 Aug 16.

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States.

Fluorescence dyes are increasingly used in brain tumor surgeries, and thus the development of simulation models is important for teaching neurosurgery trainees how to perform fluorescence-guided operations. We aimed to create a tumor model for fluorescence-guided surgery in high-grade glioma (HGG). The tumor model was generated by the following steps: creating a tumor gel with a similar consistency to HGG, selecting fluorophores at optimal concentrations with realistic color, mixing the fluorophores with tumor gel, injecting the gel into fresh pig/sheep brain, and testing resection of the tumor model under a fluorescence microscope. The optimal tumor gel was selected among different combinations of agar and gelatin. The fluorophores included fluorescein, indocyanine green (ICG), europium, chlorin e6 (Ce6), and protoporphyrin IX (PpIX). The tumor model was tested by neurosurgeons and neurosurgery trainees, and a survey was used to assess the validity of the model. In addition, the photobleaching phenomenon was studied to evaluate its influence on fluorescence detection. The best tumor gel formula in terms of consistency and tactile response was created using 100 mL water at 100°C, 0.5 g of agar, and 3 g of gelatin mixed thoroughly for 3 min. An additional 1 g of agar was added when the tumor gel cooled to 50°C. The optimal fluorophore concentration ranges were fluorescein 1.9 × 10 to 3.8 × 10 mg/mL, ICG 4.9 × 10 to 9.8 × 10 mg/mL, europium 7.0 × 10 to 1.4 × 10 mg/mL, Ce6 2.2 × 10 to 4.4 × 10 mg/mL, and PpIX 1.8 × 10 to 3.5 × 10 mg/mL. No statistical differences among fluorophores were found for face validity, content validity, and fluorophore preference. Europium, ICG, and fluorescein were shown to be relatively stable during photobleaching experiments, while chlorin e6 and PpIX had lower stability. The model can efficiently highlight the "tumor" with 3 different colors-green, yellow, or infrared green with color overlay. These models showed high face and content validity, although there was no significant difference among the models regarding the degree of simulation and training effectiveness. They are useful educational tools for teaching the key concepts of intra-axial tumor resection techniques, such as subpial dissection and nuances of fluorescence-guided surgery.
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http://dx.doi.org/10.3389/fonc.2019.00748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706957PMC
August 2019

Edwin Boldrey and Wilder Penfield's Homunculus: A Life Given by Mrs. Cantlie (In and Out of Realism).

World Neurosurg 2019 Dec 27;132:377-388. Epub 2019 Aug 27.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA. Electronic address:

For nearly 90 years, notions of the brain have been inextricably associated with a homunculus that has become embedded within medical education as the precise representation of rolandic cortical function. We sought to define the history, evolution, accuracy, and impact of this pictorial means of showing cortical representation. We mathematically defined the evolutionary accuracy of appropriate homunculi using image analysis techniques for all points defined by Penfield, Boldrey, Rasmussen, Jasper, and Erickson, calculating perpendicular distances and defining areas and distributions of rolandic and sylvian regions labeled for sensory and motor activity with comparison with all homunculi. Prerolandic sensory representation composed 13%-47% of total sensory area (mean, 29%); postrolandic motor representation composed 15%-65% of total motor area (mean, 31%). Discrepancy between cortical perpendicular length attributed to a particular function on 1937 diagrams was greater than that attributed on the 1950 homunculus (motor: mean, 74%; range, 63%-96%; sensory: mean, 66%; range, 17%-92%) (P < 0.05). The homunculus, if truly drawn according to cortical mapping evidence, could never have been recognized as near humanoid, yet it has attained epic educational and practical longevity.
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http://dx.doi.org/10.1016/j.wneu.2019.08.116DOI Listing
December 2019

Survival Outcomes Among Patients With High-Grade Glioma Treated With 5-Aminolevulinic Acid-Guided Surgery: A Systematic Review and Meta-Analysis.

Front Oncol 2019 17;9:620. Epub 2019 Jul 17.

Department of Neurosurgery, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute, Phoenix, AZ, United States.

High-grade glioma (HGG) is associated with a dismal prognosis despite significant advances in adjuvant therapies, including chemotherapy, immunotherapy, and radiotherapy. Extent of resection continues to be the most important independent prognosticator of survival. This underlines the significance of increasing gross total resection (GTR) rates by using adjunctive intraoperative modalities to maximize resection with minimal neurological morbidity. 5-aminolevulinic acid (5-ALA) is the only US Food and Drug Administration-approved intraoperative optical agent used for fluorescence-guided surgical resection of gliomas. Despite several studies on the impact of intra-operative 5-ALA use on the extent of HGG resection, a clear picture of how such usage affects patient survival is still unavailable. A systematic review was conducted of all relevant studies assessing the GTR rate and survival outcomes [overall survival (OS) and progression-free survival (PFS)] in HGG. A meta-analysis of eligible studies was performed to assess the influence of 5-ALA-guided resection on improving GTR, OS, and PFS. GTR was defined as >95% resection. Of 23 eligible studies, 19 reporting GTR rates were included in the meta-analysis. The pooled cohort had 998 patients with HGG, including 796 with newly diagnosed cases. The pooled GTR rate among patients with 5-ALA-guided resection was 76.8% (95% confidence interval, 69.1-82.9%). A comparative subgroup analysis of 5-ALA-guided vs. conventional surgery (controlling for within-study covariates) showed a 26% higher GTR rate in the 5-ALA subgroup (odds ratio, 3.8; < 0.001). There were 11 studies eligible for survival outcome analysis, 4 of which reported PFS. The pooled mean difference in OS and PFS was 3 and 1 months, respectively, favoring 5-ALA vs. control ( < 0.001). This meta-analysis shows a significant increase in GTR rate with 5-ALA-guided surgical resection, with a higher weighted GTR rate (~76%) than the pivotal phase III study (~65%). Pooled analysis showed a small yet significant increase in survival measures associated with the use of 5-ALA. Despite the statistically significant results, the low level of evidence and heterogeneity across these studies make it difficult to conclusively report an independent association between 5-ALA use and survival outcomes in HGG. Additional randomized control studies are required to delineate the role of 5-ALA in survival outcomes in HGG.
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http://dx.doi.org/10.3389/fonc.2019.00620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652805PMC
July 2019

Quantitative analysis of ipsilateral and contralateral supracerebellar infratentorial and occipital transtentorial approaches to the cisternal pulvinar: laboratory anatomical investigation.

J Neurosurg 2019 Aug 2:1-10. Epub 2019 Aug 2.

1Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.

Objective: The cisternal pulvinar is a challenging location for neurosurgery. Four approaches for reaching the pulvinar without cortical transgression are the ipsilateral supracerebellar infratentorial (iSCIT), contralateral supracerebellar infratentorial (cSCIT), ipsilateral occipital transtentorial (iOCTT), and contralateral occipital transtentorial/falcine (cOCTF) approaches. This study quantitatively compared these approaches in terms of surgical exposure and maneuverability.

Methods: Each of the 4 approaches was performed in 4 cadaveric heads (8 specimens in total). A 6-sided anatomical polygonal region was configured over the cisternal pulvinar, defined by 6 reachable anatomical points in different vectors. Multiple polygons were subsequently formed to calculate the areas of exposure. The surgical freedom of each approach was calculated as the maximum allowable working area at the proximal end of a probe, with the distal end fixed at the posterior pole of the pulvinar. Areas of exposure, surgical freedom, and the working distance (surgical depth) of all approaches were compared.

Results: No significant difference was found among the 4 different approaches with regard to the surgical depth, surgical freedom, or medial exposure area of the pulvinar. In the pairwise comparison, the cSCIT approach provided a significantly larger lateral exposure (39 ± 9.8 mm2) than iSCIT (19 ± 10.3 mm2, p < 0.01), iOCTT (19 ± 8.2 mm2, p < 0.01), and cOCTF (28 ± 7.3 mm2, p = 0.02) approaches. The total exposure area with a cSCIT approach (75 ± 23.1 mm2) was significantly larger than with iOCTT (43 ± 16.4 mm2, p < 0.01) and iSCIT (40 ± 20.2 mm2, p = 0.01) approaches (pairwise, p ≤ 0.01).

Conclusions: The cSCIT approach is preferable among the 4 compared approaches, demonstrating better exposure to the cisternal pulvinar than ipsilateral approaches and a larger lateral exposure than the cOCTF approach. Both contralateral approaches described (cSCIT and cOCTF) provided enhanced lateral exposure to the pulvinar, while the cOCTF provided a larger exposure to the lateral portion of the pulvinar than the iOCTT. Medial exposure and maneuverability did not differ among the approaches. A short tentorium may negatively impact an ipsilateral approach because the cingulate isthmus and parahippocampal gyrus tend to protrude, in which case they can obstruct access to the cisternal pulvinar ipsilaterally.
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http://dx.doi.org/10.3171/2019.4.JNS19351DOI Listing
August 2019
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