Case-control studies in neurosurgery

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J Neurosurg 121:285–296, 2014

Observational studies, such as cohort and case-control studies, are valuable instruments in evidencebased medicine. Case-control studies, in particular, are becoming increasingly popular in the neurosurgical literature due to their low cost and relative ease of execution; however, no one has yet systematically assessed these types of studies for quality in methodology and reporting.

Methods. The authors performed a literature search using PubMed/MEDLINE to identify all studies that explicitly identified themselves as “case-control” and were published in the JNS Publishing Group journals (Journal of Neurosurgery, Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery: Spine, and Neurosurgical Focus) or Neurosurgery. Each paper was evaluated for 22 descriptive variables and then categorized as having either met or missed the basic definition of a case-control study. All studies that evaluated risk factors for a well-defined outcome were considered true case-control studies. The authors sought to identify key features or phrases that were or were not predictive of a true case-control study. Those papers that satisfied the definition were further evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist.

Results. The search detected 67 papers that met the inclusion criteria, of which 32 (48%) represented true case-control studies. The frequency of true case-control studies has not changed with time. Use of odds ratios (ORs) and logistic regression (LR) analysis were strong positive predictors of true case-control studies (for odds ratios, OR 15.33 and 95% CI 4.52–51.97; for logistic regression analysis, OR 8.77 and 95% CI 2.69–28.56). Conversely, negative predictors included focus on a procedure/intervention (OR 0.35, 95% CI 0.13–0.998) and use of the word “outcome” in the Results section (OR 0.23, 95% CI 0.082–0.65). After exclusion of nested case-control studies, the negative correlation between focus on a procedure/intervention and true case-control studies was strengthened (OR 0.053, 95% CI 0.0064–0.44). There was a trend toward a negative association between the use of survival analysis or Kaplan-Meier curves and true case-control studies (OR 0.13, 95% CI 0.015–1.12). True case-control studies were no more likely than their counterparts to use a potential study design “expert” (OR 1.50, 95% CI 0.57–3.95). The overall average STROBE score was 72% (range 50–86%). Examples of reporting deficiencies were reporting of bias (28%), missing data (55%), and funding (44%).

Conclusions. The results of this analysis show that the majority of studies in the neurosurgical literature that identify themselves as “case-control” studies are, in fact, labeled incorrectly. Positive and negative predictors were identified. The authors provide several recommendations that may reverse the incorrect and inappropriate use of the term “case-control” and improve the quality of design and reporting of true case-control studies in neurosurgery.

The Impact of Sedation on Brain Mapping

Brain Mapping

Neurosurgery 75:117–123, 2014

During awake craniotomies, patients may either be awake for the entire duration of the surgical intervention (awake-awake-awake craniotomy, AAA) or initially sedated (asleep-awake-asleep craniotomy, SAS).

OBJECTIVE: To examine whether prior sedation in SAS may restrict brain mapping, we conducted neuropsychological tests in patients by means of a standardized anesthetic regimen comparable to an SAS.

METHODS: We prospectively examined patients undergoing surgery either under total intravenous anesthesia (TIVA) or under regional anesthesia with slight sedation (RAS). The tests included the DO40 picture-naming test, the digit span, the Regensburg Word Fluency Test, and the finger-tapping test. Each test was conducted 3 times for every patient in the TIVA and RAS groups, once before surgery and twice within about 35 minutes after the end of sedation. Patients undergoing AAA were examined preoperatively and intraoperatively.

RESULTS: In the AAA group, no significant difference was found between preoperative and intraoperative test results. In the TIVA and RAS groups, postoperative tests showed worse results than preoperative tests. In most tests, patients improved from the first to the second postoperative test.

CONCLUSION: Cognitive and motor performance were significantly influenced by prior sedation in the TIVA and RAS groups, but not in the AAA group. Therefore, prior sedation may be assumed to cause a change in the baselines, which may compromise brain mapping and thus endanger a patient’s neurological outcome in the case of an SAS.

The use of simulation in neurosurgical education and training

Simulation in neurosurgical training

J Neurosurg 121:228–246, 2014

There is increasing evidence that simulation provides high-quality, time-effective training in an era of resident duty-hour restrictions. Simulation may also permit trainees to acquire key skills in a safe environment, important in a specialty such as neurosurgery, where technical error can result in devastating consequences. The authors systematically reviewed the application of simulation within neurosurgical training and explored the state of the art in simulation within this specialty. To their knowledge this is the first systematic review published on this topic to date.

Methods. The authors searched the Ovid MEDLINE, Embase, and PsycINFO databases and identified 4101 articles; 195 abstracts were screened by 2 authors for inclusion. The authors reviewed data on study population, study design and setting, outcome measures, key findings, and limitations.

Results. Twenty-eight articles formed the basis of this systematic review. Several different simulators are at the neurosurgeon’s disposal, including those for ventriculostomy, neuroendoscopic procedures, and spinal surgery, with evidence for improved performance in a range of procedures. Feedback from participants has generally been favorable. However, study quality was found to be poor overall, with many studies hampered by nonrandomized design, presenting normal rather than abnormal anatomy, lack of control groups and long-term follow-up, poor study reporting, lack of evidence of improved simulator performance translating into clinical benefit, and poor reliability and validity evidence. The mean Medical Education Research Study Quality Instrument score of included studies was 9.21 ± 1.95 (± SD) out of a possible score of 18.

Conclusions. The authors demonstrate qualitative and quantitative benefits of a range of neurosurgical simulators but find significant shortfalls in methodology and design. Future studies should seek to improve study design and reporting, and provide long-term follow-up data on simulated and ideally patient outcomes.

Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects

Acute human brain responses to intracortical microelectrode arrays- challenges and future prospects

Front.Neuroeng. 7:24, 1-6

The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons.

As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns).

However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies.

Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.

Novel embalming solution for neurosurgical simulation in cadavers

Novel embalming solution for surgical simulation

J Neurosurg 120:1229–1237, 2014

Surgical simulation using postmortem human heads is one of the most valid strategies for neurosurgical research and training. The authors customized an embalming formula that provides an optimal retraction profile and lifelike physical properties while preventing microorganism growth and brain decay for neurosurgical simulations in cadavers. They studied the properties of the customized formula and compared its use with the standard postmortem processing techniques: cryopreservation and formaldehyde-based embalming.

Methods. Eighteen specimens were prepared for neurosurgical simulation: 6 formaldehyde embalmed, 6 cryopreserved, and 6 custom embalmed. The customized formula is a mixture of ethanol 62.4%, glycerol 17%, phenol 10.2%, formaldehyde 2.3%, and water 8.1%. After a standard pterional craniotomy, retraction profiles and brain stiffness were studied using an intracranial pressure transducer and monitor. Preservation time—that is, time that tissue remained in optimal condition—between specimen groups was also compared through periodical reports during a 48-hour simulation.

Results. The mean (± standard deviation) retraction pressures were highest in the formaldehyde group and lowest in the cryopreserved group. The customized formula provided a mean retraction pressure almost 3 times lower than formaldehyde (36 ± 3 vs 103 ± 14 mm Hg, p < 0.01) and very similar to cryopreservation (24 ± 6 mm Hg, p < 0.01). For research purposes, preservation time in the cryopreserved group was limited to 4 hours and was unlimited for the customized and formaldehyde groups for the duration of the experiment.

Conclusions. The customized embalming solution described herein is optimal for allowing retraction and surgical maneuverability while preventing decay. The authors were able to significantly lower the formaldehyde content as compared with that in standard formulas. The custom embalming solution has the benefits from both cryopreservation (for example, biological brain tissue properties) and formaldehyde embalming (for example, preservation time and microorganism growth prevention) and minimizes their drawbacks, that is, rapid decay in the former and stiffness in the latter. The presented embalming formula provides an important advance for neurosurgical simulations in research and teaching.

Robotics in Keyhole Transcranial Endoscope-Assisted Microsurgery

Robotics in Keyhole Transcranial Endoscope-Assisted Microsurgery

Operative Neurosurgery 10:84–96, 2014

Over the past decade, advances in image guidance, endoscopy, and tube-shaft instruments have allowed for the further development of keyhole transcranial endoscope-assisted microsurgery, utilizing smaller craniotomies and minimizing exposure and manipulation of unaffected brain tissue. Although such approaches offer the possibility of shorter operating times, reduced morbidity and mortality, and improved longterm outcomes, the technical skills required to perform such surgery are inevitably greater than for traditional open surgical techniques, and they have not been widely adopted by neurosurgeons. Surgical robotics, which has the ability to improve visualization and increase dexterity, therefore has the potential to enhance surgical performance.

OBJECTIVE: To evaluate the role of surgical robots in keyhole transcranial endoscopeassisted microsurgery.

METHODS: The technical challenges faced by surgeons utilizing keyhole craniotomies were reviewed, and a thorough appraisal of presently available robotic systems was performed.

RESULTS: Surgical robotic systems have the potential to incorporate advances in augmented reality, stereoendoscopy, and jointed-wrist instruments, and therefore to significantly impact the field of keyhole neurosurgery. To date, over 30 robotic systems have been applied to neurosurgical procedures. The vast majority of these robots are best described as supervisory controlled, and are designed for stereotactic or image-guided surgery. Few telesurgical robots are suitable for keyhole neurosurgical approaches, and none are in widespread clinical use in the field.

CONCLUSION: New robotic platforms in minimally invasive neurosurgery must possess clear and unambiguous advantages over conventional approaches if they are to achieve significant clinical penetration.

Utility of multimaterial 3D printers in creating models with pathological entities to enhance the training experience of neurosurgeons

Utility of multimaterial 3D printers in creating models with pathological entities to enhance the training experience of neurosurgeons

J Neurosurg 120:489–492, 2014

The advent of multimaterial 3D printers allows the creation of neurosurgical models of a more realistic nature, mimicking real tissues.

The authors used the latest generation of 3D printer to create a model, with an inbuilt pathological entity, of varying consistency and density. Using this model the authors were able to take trainees through the basic steps, from navigation and planning of skin flap to performing initial steps in a craniotomy and simple tumor excision.

As the technology advances, models of this nature may be able to supplement the training of neurosurgeons in a simulated operating theater environment, thus improving the training experience

The epidural approach to the Meckel’s cave

The epidural approach to the Meckel’s cave- a how I do it

Acta Neurochir (2014) 156:217–220

Meckel’s cave (MC) is a meningeal cleft lying in the middle fossa laterally to the cavernous sinus. Tumours that develop inside the MC may require a surgical resection. The authors describe the surgical technique of the intracranial epidural approach to the MC.

Methods Based upon anatomical dissection showing the relevant surgical anatomy, and illustrated by the video of an operated case, the authors detail the surgical procedure. The key point is to shave the floor of the middle fossa and skeletonize the superior orbital fissure, rotundum and ovale foramen in order to delineate the plane of dural elevation and expose the lateral wall of the MC. The rules of exposure and resection of the tumour are then shown. Variations and limitations of the approach are discussed.

Conclusion Conducted in a stepwise manner and following relevant landmarks, the epidural anterolateral approach offers a safe and reliable exposure to the diseases that develop within the MC.

Surgical strategy in grade II astrocytoma

Surgical strategy in grade II astrocytoma

Acta Neurochir (2013) 155:2227–2235

We recently demonstrated a survival benefit of early resection in unselected diffuse low-grade gliomas (LGG). However, heterogeneity within the LGG entity warrants investigation in a homogenous subgroup. Astrocytoma represents the largest subgroup of LGG, and is characterized by diffuse growth and inferior prognosis. We aimed to study the effects of early resection compared to biopsy and watchful waiting in this subgroup.

Methods Patient data was retrospectively reviewed in two neurosurgical departments with regional referral practice. In one hospital, initial diagnostic biopsies and watchful waiting was favored, while early resections guided with three-dimensional (3D) ultrasound were advocated in the other hospital. This created a natural experiment with patient management heavy influenced by residential address. In the hospitals’ histopathology databases, all adult patients diagnosed with supratentorial LGG from 1998 through 2009 were screened (n =169) and underwent blinded histopathological review. Histopathological review concluded with 117 patients with grade II astrocytomas that were included in the present study. The primary end-point was overall survival assessed by a regional comparison.

Results Early resections were performed in 51 (82 %) versus 12 (22 %) patients in the respective hospitals (p <0.001). The two patient populations were otherwise similar. Median survival was 9.7 years (95 % CI 7.5–11.9) if treated in the hospital favoring early resections compared to 5.6 years (95 % CI 3.5– 7.6) if treated at the hospital favoring biopsy and watchful waiting (p =0.047). No difference in surgical-related neurological morbidity was seen (p =0.843).

Conclusions Early 3D ultrasound guided resections improve survival, apparently without increasedmorbidity, compared to biopsy and watchful waiting in patients with diffuse World Health Organization (WHO) grade II astrocytomas.

Are readmission rates on a neurosurgical service indicators of quality of care?

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J Neurosurg 119:1043–1049, 2013

The goal of this study was to examine the reasons for early readmissions within 30 days of discharge to a major academic neurosurgical service.

Methods. A database of readmissions within 30 days of discharge between April 2009 and September 2010 was retrospectively reviewed. Clinical and administrative variables associated with readmission were examined, including age, sex, race, days between discharge and readmission, and insurance type. The readmissions were then assigned independently by 2 neurosurgeons into 1 of 3 categories: scheduled, adverse event, and unrelated. The adverse event readmissions were further subcategorized into patients readmitted although best practices were followed, those readmitted due to progression of their underlying disease, and those readmitted for preventable causes. These variables were compared descriptively.

Results. A total of 348 patients with 407 readmissions were identified, comprising 11.5% of the total 3552 admissions. The median age of readmitted patients was 55 years (range 16–96 years) and patients older than 65 years totaled 31%. There were 216 readmissions (53% of 407) for management of an adverse event that was classified as either preventable (149 patients; 37%) or unpreventable (67 patients; 16%). There were 113 patients (28%) who met readmission criteria but who were having an electively scheduled neurosurgical procedure. Progression of disease (48 patients; 12%) and treatment unrelated to primary admission (30 patients; 7%) were additional causes for readmission. There was no significant difference in the proportion of early readmissions by payer status when comparing privately insured patients and those with public or no insurance (p = 0.09).

Conclusions. The majority of early readmissions within 30 days of discharge to the neurosurgical service were not preventable. Many of these readmissions were for adverse events that occurred even though best practices were followed, or for progression of the natural history of the neurosurgical disease requiring expected but unpredictably timed subsequent treatment. Judicious care often requires readmission to prevent further morbidity or death in neurosurgical patients, and penalties for readmission will not change these patient care obligations.

Interactive presurgical simulation applying 3D techniques

Presurgical simulation 3Dimaging

J Neurosurg 119:94–105, 2013

In this paper, the authors’ goal was to report their novel presurgical simulation method applying interactive virtual simulation (IVS) using 3D computer graphics (CG) data and microscopic observation of color-printed plaster models based on these CG data in surgery for skull base and deep tumors.

Methods. For 25 operations in 23 patients with skull base or deep intracranial tumors (meningiomas, schwannomas, epidermoid tumors, chordomas, and others), the authors carried out presurgical simulation based on 3D CG data created by image analysis for radiological data. Interactive virtual simulation was performed by modifying the 3D CG data to imitate various surgical procedures, such as bone drilling, brain retraction, and tumor removal, with manipulation of a haptic device. The authors also produced color-printed plaster models of modified 3D CG data by a selective laser sintering method and observed them under the operative microscope.

Results. In all patients, IVS provided detailed and realistic surgical perspectives of sufficient quality, thereby allowing surgeons to determine an appropriate and feasible surgical approach. Surgeons agreed that in 44% of the 25 operations IVS showed high utility (as indicated by a rating of “prominent”) in comprehending 3D microsurgical anatomies for which reconstruction using only 2D images was complicated. Microscopic observation of color-printed plaster models in 12 patients provided further utility in confirming realistic surgical anatomies.

Conclusions. The authors’ presurgical simulation method applying advanced 3D imaging and modeling techniques provided a realistic environment for practicing microsurgical procedures virtually and enabled the authors to ascertain complex microsurgical anatomy, to determine the optimal surgical strategies, and also to efficiently educate neurosurgical trainees, especially during surgery for skull base and deep tumors.

Incidence of Neurosurgical Wrong-Site Surgery Before and After Implementation of the Universal Protocol

Wrong-site spinal surgery

Neurosurgery 72:590–595, 2013

Although exceedingly rare, wrong-site surgery (WSS) remains a persistent problem in the United States. The incidence is thought to be 2 to 3 per 10 000 craniotomies and about 6 to 14 per 10 000 spine surgeries. In July 2004, the Joint Commission mandated the Universal Protocol (UP) for all accredited hospitals.

OBJECTIVE: To assess the effect of UP implementation on the incidence of neurosurgical WSS at the University of Illinois College of Medicine at Peoria/Illinois Neurological Institute.

METHODS: The Morbidity and Mortality Database in the Department of Neurosurgery was reviewed to identify all recorded cases of WSS since 1999. This was compared with the total operative load (excluding endovascular procedures) of all attending neurosurgeons to determine the incidence of overall WSS. A comparison was then made between the incidences before and after UP implementation.

RESULTS: Fifteen WSS events were found with an overall incidence of 0.07% and Poisson 95% confidence interval of 8.4 to 25. All but one of these were wrong-level spine surgeries (14/15). There was only 1 recorded case of wrong-side surgery and this occurred after implementation of the UP. A statistically greater number of WSS events occurred before (n = 12) in comparison with after (n = 3) UP implementation (P < .001).

CONCLUSION: A statistically significant reduction in overall WSS was seen after implementation of the UP. This reduction can be attributed to less frequent wronglevel spine surgery. There was no case of wrong procedure or patient surgery and the 1 case of wrong-side surgery occurred after UP implementation.

A systematic review of functional magnetic resonance imaging and diffusion tensor imaging modalities used in presurgical planning of brain tumour resection

fMRI and DTI

Neurosurg Rev (2013) 36:205–214

Historically, brain tumour resection has relied upon standardised anatomical atlases and classical mapping techniques for successful resection. While these have provided adequate results in the past, the emergence of new technologies has heralded a wave of less invasive, patient-specific techniques for the mapping of brain function.

Functional magnetic resonance imaging (fMRI) and, more recently, diffusion tensor imaging (DTI) are two such techniques. While fMRI is able to highlight localisation of function within the cortex, DTI represents the only technique able to elucidate white matter structures in vivo. Used in conjunction, both of these techniques provide important presurgical information for thorough preoperative planning, as well as intraoperatively via integration into frameless stereotactic neuronavigational systems.

Together, these techniques show great promise for improved neurosurgical outcomes. While further research is required for more widespread clinical validity and acceptance, results from the literature provide a clear road map for future research and development to cement these techniques into the clinical setup of neurosurgical departments globally.

Definition of a Stereotactic 3-Dimensional Magnetic Resonance Imaging Template of the Human Insula

3D MRI template of the insula

Neurosurgery 72[ONS Suppl 1]:ons35–ons46, 2013

This study proposes a 3-dimensional (3-D) template of the insula in the bicommissural reference system with posterior commissure (PC) as the center of coordinates.

OBJECTIVE: Using the bicommissural anterior commissure (AC)–PC reference system, this study aimed to define a template and design a method for the 3-D reconstruction of the human insula that may be used at an individual level during stereotactic surgery.

METHODS: Magnetic resonance imaging (MRI)–based morphometric analysis was performed on 100 cerebral cortices with normal insulae based on a 3-step procedure: Step 1: AC-PC reference system–based reconstruction of the insula from the 1-mm thick 3-D T1-weighted MRI slices. Step 2: Digitalization and superposition of the data obtained in the 3 spatial planes. Step 3: Representation of pixels as colors on a scale corresponding to the probability of localization of each insular anatomic component.

RESULTS: The morphometric analysis of the insula confirmed our previously reported findings of a more complex shape delimited by 4 peri-insular sulci. A very significant correlation between the coordinates of the main insular structures and the length of AC-PC was demonstrated. This close correlation allowed us to develop a method that allows the 3-D reconstruction of the insula from MRI slices and only requires the localization of AC and PC. This process defines an area deemed to contain insula with 100% probability.

CONCLUSION: This 3-D reconstruction of the insula should be useful to improve its localization and other cortical areas and allow the differentiation of insular cortex from opercular cortex. KEY WORDS:

The diagnostic accuracy of brain microdialysis during surgery

Microdialysis

Acta Neurochir (2013) 155:345–353

Monitoring of brain function and metabolism during surgery may be of benefit for patient outcome. Microdialysis is the only sampling technique to date that allows continuous monitoring of drug or metabolite concentrations in the extracellular fluid of multiple tissues in the brain. This qualitative systematic review aimed to determine whether microdialysis is a valid tool for detecting changes in tissue composition as would be expected upon changes in (induced) tissue metabolic composition during brain surgery.

Methods A systematic review was conducted by performing a MEDLINE search using the terms “Intraoperative Period” (Medical Subject Heading [MeSH]) OR “Surgery” [Subheading] OR “Monitoring, Intraoperative” [MeSH] AND “Microdialysis” [MeSH] AND “Brain” [MeSH]. Two reviewers independently assessed the methodological quality of the studies. For each study the grades of recommendation were determined.

Results The search strategy yielded 46 publications in Medline. Data extraction was performed on 16 studies. The methodological quality of studies was low, with overall scores of 4 or 5. A quantitative analysis could not be performed because of lack of sufficient data. A qualitative analysis was positive with regard to the detection of different states of tissue composition by microdialysis. However, the levels of recommendation on the outcome statements were low, resulting in a grade D level of recommendation on all statements.

Conclusions The available evidence for the validity of cerebral microdialysis as a diagnostic tool during brain surgery is of low scientific quality. In order to develop cerebral microdialysis as a valid instrument for monitoring of brain metabolism during surgery, standardised clinical prospective studies in homogeneous patient populations are required.

Advanced 3-Dimensional Planning in Neurosurgery

Virtual planning of different possible approaches for the surgical treatment of a giant carotid-ophthalmic aneurysm

Neurosurgery 72:A54–A62, 2013

During the past decades, medical applications of virtual reality technology have been developing rapidly, ranging from a research curiosity to a commercially and clinically important area of medical informatics and technology. With the aid of new technologies, the user is able to process large amounts of data sets to create accurate and almost realistic reconstructions of anatomic structures and related pathologies.

As a result, a 3-dimensional (3-D) representation is obtained, and surgeons can explore the brain for planning or training. Further improvement such as a feedback system increases the interaction between users and models by creating a virtual environment. Its use for advanced 3-D planning in neurosurgery is described. Different systems of medical image volume rendering have been used and analyzed for advanced 3-D planning: 1 is a commercial “ready-to-go” system (Dextroscope, Bracco, Volume Interaction, Singapore), whereas the others are open-source-based software (3-D Slicer, FSL, and FreesSurfer).

Different neurosurgeons at our institution experienced how advanced 3-D planning before surgery allowed them to facilitate and increase their understanding of the complex anatomic and pathological relationships of the lesion. They all agreed that the preoperative experience of virtually planning the approach was helpful during the operative procedure.

Virtual reality for advanced 3-D planning in neurosurgery has achieved considerable realism as a result of the available processing power of modern computers. Although it has been found useful to facilitate the understanding of complex anatomic relationships, further effort is needed to increase the quality of the interaction between the user and the model.

Comparison of Indocyanine Green Angiography and Laser Speckle Contrast Imaging for the Assessment of Vasculature Perfusion

Neurosurgery 71:1023–1031, 2012

Assessment of the vasculature is critical for overall success in cranial vascular neurological surgery procedures. Although several methods of monitoring cortical perfusion intraoperatively are available, not all are appropriate or convenient in a surgical environment. Recently, 2 optical methods of care have emerged that are able to obtain high spatial resolution images with easily implemented instrumentation: indocyanine green (ICG) angiography and laser speckle contrast imaging (LSCI).

OBJECTIVE: To evaluate the usefulness of ICG and LSCI in measuring vessel perfusion.

METHODS: An experimental setup was developed that simultaneously collects measurements of ICG fluorescence and LSCI in a rodent model. A 785-nm laser diode was used for both excitation of the ICG dye and the LSCI illumination. A photothrombotic clot model was used to occlude specific vessels within the field of view to enable comparison of the 2 methods for monitoring vessel perfusion.

RESULTS: The induced blood flow change demonstrated that ICG is an excellent method for visualizing the volume and type of vessel at a single point in time; however, it is not always an accurate representation of blood flow. In contrast, LSCI provides a continuous and accurate measurement of blood flow changes without the need of an external contrast agent.

CONCLUSION: These 2 methods should be used together to obtain a complete understanding of tissue perfusion.

Anatomy and Pathology of the Cranial Emissary Veins: A Review With Surgical Implications

Neurosurgery 70:1312–1319, 2012 DOI: 10.1227/NEU.0b013e31824388f8

Emissary veins connect the extracranial venous system with the intracranial venous sinuses. These include, but are not limited to, the posterior condyloid, mastoid, occipital, and parietal emissary veins.

A review of the literature for the anatomy, embryology, pathology, and surgery of the intracranial emissary veins was performed.

Detailed descriptions of these venous structures are lacking in the literature, and, to the authors’, knowledge, this is the first detailed review to discuss the anatomy, pathology, anomalies, and clinical effects of the cranial emissary veins.

Our hope is that such data will be useful to the neurosurgeon during surgery in the vicinity of the emissary veins.

Microscope-Integrated Quantitative Analysis of Intraoperative Indocyanine Green Fluorescence Angiography for Blood Flow Assessment

Neurosurgery 70[ONS Suppl 1]:ons65–ons74, 2012 DOI: 10.1227/NEU.0b013e31822f7d7c

Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available.

OBJECTIVE: To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow.

METHODS: We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to halfmaximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex.

RESULTS: For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (.20, .9 , and .5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas.

CONCLUSION: Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.

Development of Stereotactic Mass Spectrometry for Brain Tumor Surgery

Neurosurgery 68:280–290, 2011 DOI: 10.1227/NEU.0b013e3181ff9cbb

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue.

OBJECTIVE: To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents.

METHODS: Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity.

RESULTS: Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence.

CONCLUSION: The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.