Evaluating soluble Axl as a biomarker for glioblastoma: A pilot study.

With current imaging, discriminating tumor progression from treatment effect following immunotherapy or oncolytic virotherapy of glioblastoma (GBM) is challenging. A blood based diagnostic biomarker would therefore be helpful. Axl is a receptor tyrosine kinase that is highly expressed by many cancers including GBM. Axl expression is regulated through enzymatic cleavage of its extracellular domain. The resulting fragment can be detected in serum as soluble Axl (sAxl). sAxl levels can distinguish patients with melanoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma from healthy controls. This is a pilot study to determine if sAxl is a candidate biomarker for GBM. The sAxl levels in the serum of 40 healthy volunteers and 20 GBM patients were determined using an enzyme-linked immunosorbent assay (ELISA). Pre- and post- operative sAxl levels were obtained. Volumetric MRI evaluation provided GBM tumor volume metrics. There was no significant difference in the sAxl levels of the volunteers (30.16±1.88 ng/ml) and GBM patients (30.74±1.96 ng/ml) p = 0.27. The postoperative sAxl levels were significantly higher than preoperative levels (32.32±2.26 ng/ml vs 30.74±1.96 ng/ml, p = 0.03). We found no correlation between tumor volume and sAxl levels. Axl expression was low or absent in 6 of 11 (55%) patient derived GBM cell lines. Given the wide range of Axl expression by GBM tumors, sAxl may not be a reliable indicator of GBM. However, given the small sample size in this study, a larger study may be considered.

The Role of 3D Tractography in Skull Base Surgery: Technological Advances, Feasibility, and Early Clinical Assessment with Anterior Skull Base Meningiomas.

Objective The aim of this study is to determine feasibility of incorporating three-dimensional (3D) tractography into routine skull base surgery planning and analyze our early clinical experience in a subset of anterior cranial base meningiomas (ACM). Methods Ninety-nine skull base endonasal and transcranial procedures were planned in 94 patients and retrospectively reviewed with a further analysis of the ACM subset. Main Outcome Measures (1) Automated generation of 3D tractography; (2) co-registration 3D tractography with computed tomography (CT), CT angiography (CTA), and magnetic resonance imaging (MRI); and (3) demonstration of real-time manipulation of 3D tractography intraoperatively. ACM subset: (1) pre- and postoperative cranial nerve function, (2) qualitative assessment of white matter tract preservation, and (3) frontal lobe fluid-attenuated inversion recovery (FLAIR) signal abnormality. Results Automated 3D tractography, with MRI, CT, and CTA overlay, was produced in all cases and was available intraoperatively. ACM subset : 8 (44%) procedures were performed via a ventral endoscopic endonasal approach (EEA) corridor and 12 (56%) via a dorsal anteromedial (DAM) transcranial corridor. Four cases (olfactory groove meningiomas) were managed with a combined, staged approach using ventral EEA and dorsal transcranial corridors. Average tumor volume reduction was 90.3 ± 15.0. Average FLAIR signal change was -30.9% ± 58.6. 11/12 (92%) patients (DAM subgroup) demonstrated preservation of, or improvement in, inferior fronto-occipital fasciculus volume. Functional cranial nerve recovery was 89% (all cases). Conclusion It is feasible to incorporate 3D tractography into the skull base surgical armamentarium. The utility of this tool in improving outcomes will require further study.

White Matter-Governed Superior Frontal Sulcus Surgical Paradigm: A Radioanatomic Microsurgical Study-Part I.

BACKGROUND: Frontal subcortical and intraventricular pathologies are traditionally accessed via transcortical or interhemispheric-transcallosal corridors. OBJECTIVE: To describe the microsurgical subcortical anatomy of the superior frontal sulcus (SFS) corridor. METHODS: Cadaveric dissections were undertaken and correlated with magnetic resonance imaging/diffusion-tensor imaging-Tractography. Surgical cases demonstrated clinical applicability. RESULTS: SFS was divided into the following divisions: proximal, precentral sulcus to coronal suture; middle, 3-cm anterior to coronal suture; and distal, middle division to the orbital crest. Anatomy was organized as layered circumferential rings projecting radially towards the ventricles: (1) outer ring: at the level of the SFS, the following lengths were measured: (A) precentral sulcus to coronal suture = 2.29 cm, (B) frontal bone projection of superior sagittal sinus (SSS) to SFS = 2.37 cm, (C) superior temporal line to SFS = 3.0 cm, and (D) orbital crest to distal part of SFS = 2.32 cm; and (2) inner ring: (a) medial to SFS, U-fibers, frontal aslant tract (FAT), superior longitudinal fasciculus I (SLF-I), and cingulum bundle, (b) lateral to SFS, U-fibers, (SLF-II), claustrocortical fibers (CCF), and inferior fronto-occipital fasciculus, and (c) intervening fibers, FAT, corona radiata, and CCF. The preferred SFS parafascicular entry point (SFSP-EP) also referred to as the Kassam-Monroy entry point (KM-EP) bisects the distance between the midpupillary line and the SSS and has the following coordinates: x = 2.3 cm (lateral to SSS), y ≥ 3.5 cm (anterior to CS), and z = parallel corona radiata and anterior limb of the internal capsule. CONCLUSION: SFS corridor can be divided into lateral, medial, and intervening white matter tract segments. Based on morphometric assessment, the optimal SFSP-EP is y ≥ 3.5 cm, x = 2.3 cm, and z = parallel to corona radiata and anterior limb of the internal capsule.

White Matter Governed Superior Frontal Sulcus Surgical Paradigm: A Radioanatomic Microsurgical Study-Part II.

BACKGROUND: Kocher's point (KP) and its variations have provided standard access to the frontal horn (FH) for over a century. Anatomic understanding of white matter tracts (WMTs) has evolved, now positioning us to better inform the optimal FH trajectory. OBJECTIVE: To (1) undertake a literature review analyzing entry points (EPs) to the FH; (2) introduce a purpose-built WMT-founded superior frontal sulcus parafascicular (SFSP)-EP also referred to as the Kassam-Monroy entry point (KM-EP); and (3) compare KM-EP with KP and variants with respect to WMTs. METHODS: (1) Literature review (PubMed database, 1892-2018): (a) stratification based on the corridor: i. ventricular catheter; ii. through-channel endoscopic; or iii. portal; (b) substratification based on intent: i. preoperatively planned or ii. intraoperative (postdural opening) for urgent ventricular drainage. (2) Anatomic comparisons of KM-EP, KP, and variants via (a) cadaveric dissections and (b) magnetic resonance-diffusion tensor imaging computational 3D modeling. RESULTS: A total of 31 studies met inclusion criteria: (a) 9 utilized KP coordinate (1 cm anterior to the coronal suture (y-axis) and 3 cm lateral of the midline (x-axis) approximated by the midpupillary line) and 22 EPs represented variations. All 31 traversed critical subcortical WMTs, specifically the frontal aslant tract, superior longitudinal fasciculus II, and inferior fronto-occipital fasciculus, whereas KM-EP (x = 2.3, y = 3.5) spares these WMTs. CONCLUSION: KP (x = 3, y = 1) conceived over a century ago, prior to awareness of WMTs, as well as its variants, anatomically place critical WMTs at risk. The KM-EP (x = 2.3, y = 3.5) is purpose built and founded on WMTs, representing anatomically safe access to the FH. Correlative clinical safety, which will be directly proportional to the size of the corridor, is yet to be established in prospective studies.

Does the method of visualization impact the performance of a new surgical task in novice subjects?

INTRODUCTION: Evolution of optical technology from two-dimensional to three-dimensional (3D) systems has come with an associated loss of stereoscopy and 3D depth perception. This report compares performance of surgical tasks in unbiased subjects using these systems. METHODS: Untrained subjects were randomized into two groups, robotically operated video optical telescopic-microscope (ROVOT) or surgical microscope (microscope). Subjects sutured and tied knots. Completion time, NASA-Task Load Index (TLX), and galvanic skin responses were analyzed. RESULTS: Intergroup analysis of suture completion time indicated that microscope use was significantly faster compared to ROVOT, whether used first or second. Regardless of which methodology was used first, the second modality was faster, indicating a transfer effect. NASA-TLX indicated that mental, performance, effort, and frustration were all greater with ROVOT. CONCLUSION: Task completion time and perceived effort were greater with ROVOT. Task completion times improved with repetition regardless of visual modality.

Initial Experience with Exoscopic-Based Intraoperative Indocyanine Green Fluorescence Video Angiography in Cerebrovascular Surgery: A Preliminary Case Series Showing Feasibility, Safety, and Next-Generation Handheld Form-Factor.

BACKGROUND: Native vessel patency and residual lesion are primary sources of morbidity in cerebrovascular surgery (CVS) that require real-time visualization to inform surgical judgment, as is available in endovascular procedures. Micro Doppler and microscopy-based indocyanine green (ICG) fluorescence are promising evolutions compared with intraoperative angiography (IA), and digital subtraction angiography (DSA) remains the gold standard. Exoscopic visualization in CVS is emerging; however, the feasibility of exoscopic-based ICG (ICG-E) for CVS has not yet been reported. To objective of the study was to provide initial experience with ICG-E video angiography in CVS. METHODS: Retrospective study in which 2 ICG-E form-factors (exoscopic-coupled or self-contained handheld imager) were used to determine native vessel patency and residual and compared with DSA. RESULTS: Eleven patients (8 aneurysms, 3 arteriovenous malformations [AVMs]) were included. ICG-E was feasible in all, providing real-time information leading to operative decisions affecting surgical judgment. For aneurysms, discordance of IA with ICG-E and DSA was 12%. In 1 patient, IA showed non-flow-restrictive branch stenosis; however, both ICG and DSA showed patency. All AVMs were fully obliterated, with 100% concordance among all modalities. ICG averaged 4.2 mg dose/run (1-4 doses/case); 1.25 mg was the lowest dose allowing visualization with no advantage with escalating dosages. There were no intraoperative/perioperative complications. CONCLUSIONS: In this preliminary study, ICG-E was safe and feasible, providing real-time visualization informing surgical decision making. The last 4 cases (2 aneurysms and 2 AVMs) evolved toward a portable handheld device, a readily accessible real-time modality providing contextual anatomic and flow visualization. Larger studies are needed to assess broader safety, dose escalation, and efficacy.

An Anatomically-Based Endoscopic Endonasal Model to Navigate the Anterior Ventral Skull Base.

BACKGROUND: Endoscopic endonasal approaches to access the sellar and parasellar regions are challenging in the face of anatomical variations or pathologic conditions. We propose an anatomically-based model including the orbitosellar line (OSL), critical oblique foramen line (COFL), and paramedial anterior line (PAL) facilitating safe, superficial-to-deep dissection triangulating upon the medial opticocarotid recess. METHODS: Five cadaveric heads were dissected to systematically expose the OSL, COFL, and PAL, illustrated with image guidance. Application of the coordinate system and a 6-step dissection sequence is described. RESULTS: The coordinate system consists of 1) the OSL, connecting a) the anterior orbital point, junction of the anterior buttress of the middle turbinate with the agger nasi region, located 34.3 ± 0.9 mm above the intersection of the vertical plane of the lacrimal crest, and the orthogonal plane of the maxillo-ethmoidal suture; b) the posterior orbital point, junction of the optic canal with the lamina papyracea, located 4 ± 0.7 mm below the posterior ethmoidal artery; and c) the medial opticocarotid recess; 2) COFL (15 ± 2.8 mm), connecting the palatovaginal canal, vidian canal, and foramen rotundum; and 3) PAL (39 ± 0.06 mm), connecting the vidian canal with the posterior ethmoidal artery. CONCLUSIONS: OSL, COFL, and PAL form an anatomically-based model for the systematic exposure when accessing the parasellar and sellar regions. Preliminary anatomical data suggest that this model may be of value when normal anatomy is distorted by pathology or anatomic variations.

Awake Surgical Management of Third Ventricular Tumors: A Preliminary Safety, Feasibility, and Clinical Applications Study.

BACKGROUND: Endoscopic and microneurosurgical approaches to third ventricular lesions are commonly performed under general anesthesia. OBJECTIVE: To report our initial experience with awake transsulcal parafascicular corridor surgery (TPCS) of the third ventricle and its safety, feasibility, and limitations. METHODS: A total of 12 cases are reviewed: 6 colloid cysts, 2 central neurocytomas, 1 papillary craniopharyngioma, 1 basal ganglia glioblastoma, 1 thalamic glioblastoma, and 1 ependymal cyst. Lesions were approached using TPCS through the superior frontal sulcus. Pre-, intra-, and postoperative neurocognitive (NC) testing were performed on all patients. RESULTS: No cases required conversion to general anesthesia. Awake anesthesia changed intraoperative management in 4/12 cases with intraoperative cognitive changes that required port re-positioning; 3/4 recovered. Average length of stay (LOS) was 6.1 d ± 6.6. Excluding 3 outliers who had preoperative NC impairment, the average LOS was 2.5 d ± 1.2. Average operative time was 3.00 h ± 0.44. Average awake anesthesia time was 5.05 h ± 0.54. There were no mortalities. CONCLUSION: This report demonstrated the feasibility and safety of awake third ventricular surgery, and was not limited by pathology, size, or vascularity. The most significant factor impacting LOS was preoperative NC deficit. The most significant risk factor predicting a permanent NC deficit was preoperative 2/3 domain impairment combined with radiologic evidence of invasion of limbic structures - defined as a "NC resilience/reserve" in our surgical algorithm. Larger efficacy studies will be required to demonstrate the validity of the algorithm and impact on long-term cognitive outcomes, as well as generalizability of awake TPCS for third ventricular surgery.

Microsurgical Anatomy of the Vertical Rami of the Superior Longitudinal Fasciculus: An Intraparietal Sulcus Dissection Study.

BACKGROUND: A number of vertical prolongations of the superior longitudinal fasciculus, which we refer to as the vertical rami (Vr), arise at the level of the supramarginal gyrus, directed vertically toward the parietal lobe. OBJECTIVE: To provide the first published complete description of the white matter tracts (WMT) of the Vr, their relationship to the intraparietal and parieto-occipital sulci (IPS-POS complex), and their importance in neurosurgical approaches to the parietal lobe. METHODS: Subcortical dissections of the Vr and WMT of the IPS were performed. Findings were correlated with a virtual dissection using high-resolution diffusion tensor imaging (DTI) tractography data derived from the Human Connectome Project. Example planning of a transparietal, transsulcal operative corridor is demonstrated using an integrated neuronavigation and optical platform. RESULTS: The Vr were shown to contain component fibers of the superior longitudinal fasciculus (SLF)-II and SLF-III, with contributions from the middle longitudinal fasciculus merging into the medial bank of the IPS. The anatomic findings correlated well with DTI tractography. The line extending from the lateral extent of the POS to the IPS marks an ideal sulcal entry point that we have termed the IPS-POS Kassam-Monroy (KM) Point, which can be used to permit a safe parafascicular surgical trajectory to the trigone. CONCLUSION: The Vr are a newly conceptualized group of tracts merging along the banks of the IPS, mediating connectivity between the parietal lobe and dorsal stream/SLF. We suggest a refined surgical trajectory to the ventricular atrium utilizing the posterior third of the IPS, at or posterior to the IPS-POS Point, in order to mitigate risk to the Vr and its considerable potential for postsurgical morbidity.

Reanalyzing the "far medial" (transcondylar-transtubercular) approach based on three anatomical vectors: the ventral posterolateral corridor.

Endoscopic endonasal access to the jugular foramen and occipital condyle - the transcondylar-transtubercular approach - is anatomically complex and requires detailed knowledge of the relative position of critical neurovascular structures, in order to avoid inadvertent injury and resultant complications. However, access to this region can be confusing as the orientation and relationships of osseous, vascular, and neural structures are very much different from traditional dorsal approaches. This review aims at providing an organizational construct for a more understandable framework in accessing the transcondylar-transtubercular window. The region can be conceptualized using a three-vector coordinate system: vector 1 represents a dorsal or ventral corridor, vector 2 represents the outer and inner circumferential anatomical limits; in an "onion-skin" fashion, key osseous, vascular, and neural landmarks are organized based on a 360-degree skull base model, and vector 3 represents the final core or target of the surgical corridor. The creation of an organized "global-positioning system" may better guide the surgeon in accessing the far-medial transcondylar-transtubercular region, and related pathologies, and help understand the surgical limits to the occipital condyle and jugular foramen - the ventral posterolateral corridor - via the endoscopic endonasal approach.

The Surgical White Matter Chassis: A Practical 3-Dimensional Atlas for Planning Subcortical Surgical Trajectories.

BACKGROUND: The imperative role of white matter preservation in improving surgical functional outcomes is now recognized. Understanding the fundamental white matter framework is essential for translating the anatomic and functional literature into practical strategies for surgical planning and neuronavigation. OBJECTIVE: To present a 3-dimensional (3-D) atlas of the structural and functional scaffolding of human white matter-ie, a "Surgical White Matter Chassis (SWMC)"-that can be used as an organizational tool in designing precise and individualized trajectory-based neurosurgical corridors. METHODS: Preoperative diffusion tensor imaging magnetic resonance images were obtained prior to each of our last 100 awake subcortical resections, using a clinically available 3.0 Tesla system. Tractography was generated using a semiautomated deterministic global seeding algorithm. Tract data were conceptualized as a 3-D modular chassis based on the 3 major fiber types, organized along median and paramedian planes, with special attention to limbic and neocortical association tracts and their interconnections. RESULTS: We discuss practical implementation of the SWMC concept, and highlight its use in planning select illustrative cases. Emphasis has been given to developing practical understanding of the arcuate fasciculus, uncinate fasciculus, and vertical rami of the superior longitudinal fasciculus, which are often-neglected fibers in surgical planning. CONCLUSION: A working knowledge of white matter anatomy, as embodied in the SWMC, is of paramount importance to the planning of parafascicular surgical trajectories, and can serve as a basis for developing reliable safe corridors, or modules, toward the goal of "zero-footprint" transsulcal access to the subcortical space.

Initial experience with a robotically operated video optical telescopic-microscope in cranial neurosurgery: feasibility, safety, and clinical applications.

OBJECTIVE The move toward better, more effective optical visualization in the field of neurosurgery has been a focus of technological innovation. In this study, the authors' objectives are to describe the feasibility and safety of a new robotic optical platform, namely, the robotically operated video optical telescopic-microscope (ROVOT-m), in cranial microsurgical applications. METHODS A prospective database comprising patients who underwent a cranial procedure between April 2015 and September 2016 was queried, and the first 200 patients who met the inclusion criteria were selected as the cohort for a retrospective chart review. Only adults who underwent microsurgical procedures in which the ROVOT-m was used were considered for the study. Preoperative, intraoperative, and postoperative data were retrieved from electronic medical records. The authors address the feasibility and safety of the ROVOT-m by studying various intraoperative variables and by reporting perioperative morbidity and mortality, respectively. To assess the learning curve, cranial procedures were categorized into 6 progressively increasing complexity groups. The main categories of pathology were I) intracerebral hemorrhages (ICHs); II) intraaxial tumors involving noneloquent regions or noncomplex extraaxial tumors; III) intraaxial tumors involving eloquent regions; IV) skull base pathologies; V) intraventricular lesions; and VI) cerebrovascular lesions. In addition, the entire cohort was evenly divided into early and late cohorts. RESULTS The patient cohort comprised 104 female (52%) and 96 male (48%) patients with a mean age of 56.7 years. The most common pathological entities encountered were neoplastic lesions (153, 76.5%), followed by ICH (20, 10%). The distribution of cases by complexity categories was 11.5%, 36.5%, 22%, 20%, 3.5%, and 6.5% for Categories I, II, II, IV, V, and VI, respectively. In all 200 cases, the surgical goal was achieved without the need for intraoperative conversion. Overall, the authors encountered 3 (1.5%) major neurological morbidities and 6 (3%) 30-day mortalities. Four of the 6 deaths were in the ICH group, resulting in a 1% mortality rate for the remainder of the cohort when excluding these patients. None of the intraoperative complications were considered to be attributable to the visualization provided by the ROVOT-m. When comparing the early and late cohorts, the authors noticed an increase in the proportion of higher-complexity surgeries (Categories IV-VI), from 23% in the early cohort, to 37% in the late cohort (p = 0.030). In addition, a significant reduction in operating room setup time was demonstrated (p < 0.01). CONCLUSIONS The feasibility and safety of the ROVOT-m was demonstrated in a wide range of cranial microsurgical applications. The authors report a gradual increase in case complexity over time, representing an incremental acquisition of experience with this technology. A learning curve of both setup and execution phases should be anticipated by new adopters of the robot system. Further prospective studies are required to address the efficacy of ROVOT-m. This system may play a role in neurosurgery as an integrated platform that is applicable to a variety of cranial procedures.

The Operating Room of the Future Versus the Future of the Operating Room.

Technological advancement in the operating room is evolving into a dynamic system mirroring that of the aeronautics industry. Through data visualization, information is continuously being captured, collected, and stored on a scalable informatics platform for rapid, intuitive, iterative learning. The authors believe this philosophy (paradigm) will feed into an intelligent informatics domain fully accessible to all and geared toward precision, cell-based therapy in which tissue can be targeted and interrogated in situ. In the future, the operating room will be a venue that facilitates this real-time tissue interrogation, which will guide in situ therapeutics to restore the state of health.

An Intraventricular Schwannoma with Associated Hydrocephalus and Ventricular Entrapment: A Case Report.

Intraventricular schwannomas are rare primary brain tumors, with fewer than 25 cases reported in the literature. Here, we present the case of a 20-year-old male patient with a 2 year history of blurry vision and dysesthesia involving his right occiput and upper neck. Imaging demonstrated a homogeneously enhancing mass located within the atrium of the right lateral ventricle with associated right lateral ventricular entrapment. Pathology confirmed the tumor to be an intraventricular schwannoma. Imaging findings, presentation, complications, and treatment options for intraventricular schwannomas are described.

Microbiology for Radiologists: How to Minimize Infection Transmission in the Radiology Department.

The implementation of standardized infection control and prevention practices is increasingly relevant as modern radiology practice evolves into its more clinical role. Current Centers for Disease Control and Prevention, National Institutes of Health, and World Health Organization guidelines for the proper use of personal protective equipment, decontamination of reusable medical equipment, and appropriate management of bloodborne pathogen exposures will be reviewed. Standard precautions apply to all patients at all times and are the mainstay of infection control. Proper hand hygiene includes washing hands with soap and water when exposed to certain infectious particles, such as Clostridium difficile spores, which are not inactivated by alcohol-based hand rubs. The appropriate use of personal protective equipment in accordance with recommendations from the Centers for Disease Control and Prevention includes wearing a surgical mask during lumbar puncture. Because radiologists may perform lumbar punctures for patients with prion disease, it is important to appreciate that incineration is the most effective method of inactivating prion proteins. However, there is currently no consensus recommendation on the decontamination of prion-contaminated reusable items associated with lumbar puncture, and institutional policies should be consulted for directed management. In the event of a needlestick injury, radiology staff must be able to quickly provide appropriate initial management and seek medical attention, including laboratory testing for bloodborne pathogens.

Parkinson's disease: an inquiry into the etiology and treatment.

Parkinson's disease affects over one million people in the United States. Although there have been remarkable advances in uncovering the pathogenesis of this disabling disorder, the etiology is speculative. Medical treatment and operative procedures provide symptomatic relief only. Compression of the cerebral peduncle of the midbrain by the posterior cerebral artery in a patient with Parkinson's Disease (Parkinson's Disease) was noted on magnetic resonance imaging (MRI) scan and at operation in a patient with trigeminal neuralgia. Following the vascular decompression of the trigeminal nerve, the midbrain was decompressed by mobilizing and repositioning the posterior cerebral artery The patient's Parkinson's signs disappeared over a 48-hour period. They returned 18 months later with contralateral peduncle compression. A blinded evaluation of MRI scans of Parkinson's patients and controls was performed. MRI scans in 20 Parkinson's patients and 20 age and sex matched controls were evaluated in blinded fashion looking for the presence and degree of arterial compression of the cerebral peduncle. The MRI study showed that 73.7 percent of Parkinson's Disease patients had visible arterial compression of the cerebral peduncle. This was seen in only 10 percent of control patients (two patients, one of whom subsequently developed Parkinson's Disease); thus 5 percent. Vascular compression of the cerebral peduncle by the posterior cerebral artery may be associated with Parkinson's Disease in some patients. Microva-scular decompression of that artery away from the peduncle may be considered for treatment of Parkinson's Disease in some patients.