Decision-Making for Preventive Interventions in Asymptomatic Patients.

The decision to treat an incidental finding in an asymptomatic patient results from careful risk-benefit consideration and is often challenging. One of the main aspects is after how many years the group who underwent the intervention and faced the immediate treatment complications will gain a treatment benefit over the conservatively managed group, which maintains a lower but ongoing risk. We identify a common error in decision-making. We illustrate how a risk-based approach using the classical break-even point at the Kaplan-Meier curves can be misleading and advocate for using an outcome-based approach, counting the cumulative number of lost quality-adjusted life years instead. In clinical practice, we often add together the yearly risk of the natural course up to the time point where the number equals the risk of the intervention and assume that the patient will benefit from an intervention beyond this point in time. It corresponds to the crossing of the Kaplan-Meier curves. However, because treatment-related poor outcome occurs at the time of the intervention, while the poor outcome in the conservative group occurs over a given time period, the true benefit of retaining more quality-adjusted life years in the interventional group emerges at a much later time. To avoid overtreatment of patients with asymptomatic diseases, decision-making should be outcome-based with counting the cumulative loss of quality-adjusted life years, rather than risk-based, comparing the interventional risk with the ongoing yearly risk of the natural course.

Simultaneous multi-region detection of GABA+ and Glx using 3D spatially resolved SLOW-editing and EPSI-readout at 7T.

GABA+ and Glx (glutamate and glutamine) are widely studied metabolites, yet the commonly used magnetic resonance spectroscopy (MRS) techniques have significant limitations, including sensitivity to B0 and B1+-inhomogeneities, limited bandwidth of MEGA-pulses, high SAR which is accentuated at 7T. To address these limitations, we propose SLOW-EPSI method, employing a large 3D MRSI coverage and achieving a high resolution down to 0.26 ml. Simulation results demonstrate the robustness of SLOW-editing for both GABA+ and Glx against B0 and B1+-inhomogeneities within the range of [-0.3, +0.3] ppm and [40 %, 250 %], respectively. Two protocols, both utilizing a 70 mm thick FOV slab, were employed to target distinct brain regions in vivo, differentiated by their orientation: transverse and tilted. Protocol 1 (n = 11) encompassed 5 locations (cortical gray matter, white matter, frontal lobe, parietal lobe, and cingulate gyrus). Protocol 2 (n = 5) involved 9 locations (cortical gray matter, white matter, frontal lobe, occipital lobe, cingulate gyrus, caudate nucleus, hippocampus, putamen, and inferior thalamus). Quantitative analysis of GABA+ and Glx was conducted in a stepwise manner. First, B1+/B1--inhomogeneities were corrected using water reference data. Next, GABA+ and Glx values were calculated employing spectral fitting. Finally, the GABA+ level for each selected region was compared to the global Glx within the same subject, generating the GABA+/Glx_global ratio. Our findings from two protocols indicate that the GABA+/Glx_global level in cortical gray matter was approximately 16 % higher than in white matter. Elevated GABA+/Glx_global levels acquired with protocol 2 were observed in specific regions such as the caudate nucleus (0.118±0.067), putamen (0.108±0.023), thalamus (0.092±0.036), and occipital cortex (0.091±0.010), when compared to the cortical gray matter (0.079±0.012). Overall, our results highlight the effectiveness of SLOW-EPSI as a robust and efficient technique for accurate measurements of GABA+ and Glx at 7T. In contrast to previous SVS and 2D-MRSI based editing sequences with which only one or a limited number of brain regions can be measured simultaneously, the method presented here measures GABA+ and Glx from any brain area and any arbitrarily shaped volume that can be flexibly selected after the examination. Quantification of GABA+ and Glx across multiple brain regions through spectral fitting is achievable with a 9-minute acquisition. Additionally, acquisition times of 18-27 min (GABA+) and 9-18 min (Glx) are required to generate 3D maps, which are constructed using Gaussian fitting and peak integration.

Robustness of the wide-field imaging Mueller polarimetry for brain tissue differentiation and white matter fiber tract identification in a surgery-like environment: an ex vivo study.

During neurooncological surgery, the visual differentiation of healthy and diseased tissue is often challenging. Wide-field imaging Muller polarimetry (IMP) is a promising technique for tissue discrimination and in-plane brain fiber tracking in an interventional setup. However, the intraoperative implementation of IMP requires realizing imaging in the presence of remanent blood, and complex surface topography resulting from the use of an ultrasonic cavitation device. We report on the impact of both factors on the quality of polarimetric images of the surgical resection cavities reproduced in fresh animal cadaveric brains. The robustness of IMP is observed under adverse experimental conditions, suggesting a feasible translation of IMP for in vivo neurosurgical applications.

Exploring Novel Innovation Strategies to Close a Technology Gap in Neurosurgery: HORAO Crowdsourcing Campaign.

BACKGROUND: Scientific research is typically performed by expert individuals or groups who investigate potential solutions in a sequential manner. Given the current worldwide exponential increase in technical innovations, potential solutions for any new problem might already exist, even though they were developed to solve a different problem. Therefore, in crowdsourcing ideation, a research question is explained to a much larger group of individuals beyond the specialist community to obtain a multitude of diverse, outside-the-box solutions. These are then assessed in parallel by a group of experts for their capacity to solve the new problem. The 2 key problems in brain tumor surgery are the difficulty of discerning the exact border between a tumor and the surrounding brain, and the difficulty of identifying the function of a specific area of the brain. Both problems could be solved by a method that visualizes the highly organized fiber tracts within the brain; the absence of fibers would reveal the tumor, whereas the spatial orientation of the tracts would reveal the area's function. To raise awareness about our challenge of developing a means of intraoperative, real-time, noninvasive identification of fiber tracts and tumor borders to improve neurosurgical oncology, we turned to the crowd with a crowdsourcing ideation challenge. OBJECTIVE: Our objective was to evaluate the feasibility of a crowdsourcing ideation campaign for finding novel solutions to challenges in neuroscience. The purpose of this paper is to introduce our chosen crowdsourcing method and discuss it in the context of the current literature. METHODS: We ran a prize-based crowdsourcing ideation competition called HORAO on the commercial platform HeroX. Prize money previously collected through a crowdfunding campaign was offered as an incentive. Using a multistage approach, an expert jury first selected promising technical solutions based on broad, predefined criteria, coached the respective solvers in the second stage, and finally selected the winners in a conference setting. We performed a postchallenge web-based survey among the solvers crowd to find out about their backgrounds and demographics. RESULTS: Our web-based campaign reached more than 20,000 people (views). We received 45 proposals from 32 individuals and 7 teams, working in 26 countries on 4 continents. The postchallenge survey revealed that most of the submissions came from single solvers or teams working in engineering or the natural sciences, with additional submissions from other nonmedical fields. We engaged in further exchanges with 3 out of the 5 finalists and finally initiated a successful scientific collaboration with the winner of the challenge. CONCLUSIONS: This open innovation competition is the first of its kind in medical technology research. A prize-based crowdsourcing ideation campaign is a promising strategy for raising awareness about a specific problem, finding innovative solutions, and establishing new scientific collaborations beyond strictly disciplinary domains.

Accurate prediction of isocitrate dehydrogenase -mutation status of gliomas using SLOW-editing magnetic resonance spectroscopic imaging at 7 T MR.

Background: 2-hydroxy-glutarate (2HG) is a metabolite that accumulates in isocitrate dehydrogenase (IDH)-mutated gliomas and can be detected noninvasively using MR spectroscopy. However, due to the low concentration of 2HG, established magnetic resonance spectroscopic imaging (MRSI) techniques at the low field have limitations with respect to signal-to-noise and to the spatial resolution that can be obtained within clinically acceptable measurement times. Recently a tailored editing method for 2HG detection at 7 Tesla (7 T) named SLOW-EPSI was developed. The underlying prospective study aimed to compare SLOW-EPSI to established techniques at 7 T and 3 T for IDH-mutation status determination. Methods: The applied sequences were MEGA-SVS and MEGA-CSI at both field strengths and SLOW-EPSI at 7 T only. Measurements were performed on a MAGNETOM-Terra 7 T MR-scanner in clinical mode using a Nova 1Tx32Rx head coil and on a 3 T MAGNETOM-Prisma scanner with a standard 32-channel head coil. Results: Fourteen patients with suspected glioma were enrolled. Histopathological confirmation was available in 12 patients. IDH mutation was confirmed in 9 out of 12 cases and 3 cases were characterized as IDH wildtype. SLOW-EPSI at 7 T showed the highest accuracy for IDH-status prediction (91.7% accuracy, 11 of the 12 predictions correct with 1 false negative case). At 7 T, MEGA-CSI had an accuracy of 58.3% and MEGA-SVS had an accuracy of 75%. At 3 T, MEGA-CSI showed an accuracy of 63.6% and MEGA-SVS of 33.3%. The co-edited cystathionine was detected in 2 out of 3 oligodendroglioma cases with 1p/19q codeletion. Conclusions: Depending on the pulse sequence, spectral editing can be a powerful tool for the noninvasive determination of the IDH status. SLOW-editing EPSI sequence is the preferable pulse sequence when used at 7 T for IDH-status characterization.

A standardized model for in vitro testing of sutures and patches for watertight dural closure.

OBJECTIVE: CSF leaks are common complications of spinal and cranial surgeries. Several dural grafts and suture techniques are available to achieve watertight dural closure, but the effectiveness of these techniques remains unclear. The authors developed a standardized in vitro model to test available grafts and suture techniques alone or in combination to find the technique with the most watertight dural closure. METHODS: A fluid chamber with a dural fixation device, infusion pump, pressure gauge, and porcine pericardium as a dural equivalent was assembled to provide the reusable device for testing. The authors performed dural closure in 4 different fashions, as follows: A) using running versus simple interrupted suture technique and different suture materials to close a 3-cm incision; B) selecting commonly used sealants and dural patches in combination with a running suture; C) performing duraplasty (1.5 × 1.5-cm square defect) with different dural substitutes in a stand-alone fashion; and D) performing duraplasty with different dural substitutes in a double-layer fashion. Each technique was tested 6 times. The hydrostatic burst pressure (BP) was measured and compared using the Kruskal-Wallis test or the Mann-Whitney U-test. Values are reported as mean ± SD. RESULTS: There was no significant difference between the running and simple interrupted suture technique (p = 0.79). Adding a patch or sealant to a suture resulted in a 1.7- to 14-fold higher BP compared to solitary suture closure (36.2 ± 24.27 cm H2O and 4.58 ± 1.41 cm H2O, respectively; p < 0.001). The highest BP was achieved by adding DuraSeal or TachoSil (82.33 ± 12.72 cm H2O and 74.17 ± 12.64 cm H2O, respectively). For closing a square defect, using a double-layer duraplasty significantly increased BP by a factor of 4-12 compared to a single-layer duraplasty (31.71 ± 12.62 cm H2O vs 4.19 ± 0.88 cm H2O, respectively; p < 0.001). The highest BP was achieved with the combination of Lyomesh and TachoSil (43.67 ± 11.45 cm H2O). CONCLUSIONS: A standardized in vitro model helps to objectify the watertightness of dural closure. It allows testing of sutures and dural grafts alone or in combination. In the authors' testing, a running 6-0 monofilament polypropylene suture combined with DuraSeal or TachoSil was the technique achieving the highest BP. For the duraplasty of square defects, the double-layer technique showed the highest efficacy.

Spontaneous Intracranial Hypotension Without CSF Leakage-Concept of a Pathological Cranial to Spinal Fluid Shift.

Objective: Spontaneous intracranial hypotension (SIH) is typically caused by CSF leakage from a spinal dural tear, a meningeal diverticulum, or a CSF venous fistula. However, some patients present with classic orthostatic symptoms and typical intracranial imaging findings without evidence of CSF leakage despite repeated diagnostic work-up. This article aims to elaborate a hypothesis that would explain a pathologically increased orthostatic shift of CSF from the cranial to the spinal compartment in the absence of a CSF leak. Medical Hypothesis: The symptoms of SIH are caused by a decrease in intracranial CSF volume, intracranial hypotension, and downward displacement of intracranial structures. A combination of pathologically increased spinal compliance, decreased intracranial CSF volume, low CSF outflow resistance, and decreased venous pressure might result in a pathological orthostatic cranial-to-spinal CSF shift. Thus, in rare cases, intracranial hypotension may occur in the absence of CSF leakage from the dural sac. Conclusion: We propose a pathophysiological concept for the subgroup of SIH patients with typical cranial imaging findings and no evidence of CSF leakage. In these patients, reducing the compliance or the volume of the spinal compartment seems to be the appropriate therapeutic strategy.

Exploring Novel Funding Strategies for Innovative Medical Research: The HORAO Crowdfunding Campaign.

BACKGROUND: The rise of the internet and social media has boosted online crowdfunding as a novel strategy to raise funds for kick-starting projects, but it is rarely used in science. OBJECTIVE: We report on an online crowdfunding campaign launched in the context of the neuroscience project HORAO. The aim of HORAO was to develop a noninvasive real-time method to visualize neuronal fiber tracts during brain surgery in order to better delineate tumors and to identify crucial cerebral landmarks. The revenue from the crowdfunding campaign was to be used to sponsor a crowdsourcing campaign for the HORAO project. METHODS: We ran a 7-week reward-based crowdfunding campaign on a national crowdfunding platform, offering optional material and experiential rewards in return for a contribution toward raising our target of Swiss francs (CHF) 50,000 in financial support (roughly equivalent to US $50,000 at the time of the campaign). We used various owned media (websites and social media), as well as earned media (press releases and news articles) to raise awareness about our project. RESULTS: The production of an explanatory video took 60 hours, and 31 posts were published on social media (Facebook, Instagram, and Twitter). The campaign raised a total of CHF 69,109. Approximately half of all donations came from donors who forwent a reward (CHF 28,786, 48.74%); the other half came from donors who chose experiential and material rewards in similar proportions (CHF 14,958, 25.33% and CHF 15,315.69, 25.93%, respectively). Of those with an identifiable relationship to the crowdfunding team, patients and their relatives contributed the largest sum (CHF 17,820, 30.17%), followed by friends and family (CHF 9288, 15.73%) and work colleagues (CHF 6028, 10.21%), while 43.89% of funds came from donors who were either anonymous or had an unknown relationship to the crowdfunding team. Patients and their relatives made the largest donations, with a median value of CHF 200 (IQR 90). CONCLUSIONS: Crowdfunding proved to be a successful strategy to fund a neuroscience project and to raise awareness of a specific clinical problem. Focusing on potential donors with a personal interest in the issue, such as patients and their relatives in our project, is likely to increase funding success. Compared with traditional grant applications, new skills are needed to explain medical challenges to the crowd through video messages and social media.

Visualization of White Matter Fiber Tracts of Brain Tissue Sections With Wide-Field Imaging Mueller Polarimetry.

Identification of white matter fiber tracts of the brain is crucial for delineating the tumor border during neurosurgery. A custom-built Mueller polarimeter was used in reflection configuration for the wide-field imaging of thick sections of fixed human brain and fresh calf brain. The maps of the azimuth of the fast optical axis of linear birefringent medium reconstructed from the experimental Mueller matrix images of the specimen by applying a non-linear data compression algorithm showed a strong correlation with the silver-stained sample histology image, which is the gold standard for ex-vivo brain fiber tract visualization. The polarimetric maps of fresh calf brain tissue demonstrated the same trends in the depolarization, the scalar retardance and the azimuth of the fast optical axis as seen in fixed human brain tissue. Thus, label-free imaging Mueller polarimetry shows promise as an efficient intra-operative modality for the visualization of healthy brain white matter fiber tracts, which could improve the accuracy of tumor border detection and, ultimately, patient outcomes.

Continuous dynamic mapping to avoid accidental injury of the facial nerve during surgery for large vestibular schwannomas.

In vestibular schwannoma (VS) surgery postoperative facial nerve (CN VII) palsy is reducing quality of life. Recently, we have introduced a surgical suction device for continuous dynamic mapping to provide feedback during tumor resection without switching to a separate stimulation probe. The objective was to evaluate the reliability of this method to avoid CN VII injury. Continuous mapping for CN VII was performed in large VS (08/2014 to 11/2017) additionally to standard neurophysiological techniques. A surgical suction-and-mapping probe was used for surgical dissection and continuous monopolar stimulation. Stimulation was performed with 0.05-2 mA intensities (0.3 msec pulse duration, 2.0 Hz). Postoperative CNVII outcome was assessed by the House-Brackmann-Score (HBS) after 1 week and 3 months following surgery. Twenty patients with Koos III (n = 2; 10%) and Koos IV (n = 18; 90%) VS were included. Preoperative HBS was 1 in 19 patients and 2 in 1 patient. Dynamic mapping reliably indicated the facial nerve when resection was close to 5-10 mm. One week after surgery, 7 patients presented with worsening in HBS. At 3 months, 4 patients' facial weakness had resolved and 3 patients (15%) had an impairment of CN VII (HBS 3 and 4). Of the 3 patients, near-total removal was attempted in 2. The continuous dynamic mapping method using an electrified surgical suction device might be a valuable additional tool in surgery of large VS. It provides real-time feedback indicating the presence of the facial nerve within 5-10 mm depending on stimulation intensity and may help in avoiding accidental injury to the nerve.

Ultrasonic quantification of cerebral perfusion in acute anterior circulation occlusive stroke-A comparative challenge of the refill- and the bolus-kinetics approach.

PURPOSE: To prospectively evaluate the potential of semi-quantitative evaluation of cerebral perfusion in acute ischemic stroke by comparing two established ultrasound approaches. MATERIALS AND METHODS: Consecutive inclusion of patients with acute occlusion of middle cerebral artery (MCA) confirmed by either magnetic resonance imaging (MRI) or computed tomography (CT) perfusion imaging qualifying for interventional therapy. Comparison of bilateral high mechanical index (MI) bolus-kinetics (HighMiB) and unilateral low MI refill-kinetics (LowMiR) performed before specific treatment. RESULTS: In 16/31 patients HighMiB was eligible, in 8/31 patients LowMiR was eligible. In six out of these eight patients both HighMiB and LowMiR were eligible for direct comparison. In MR/CT perfusion imaging of the 16 patients eligible for HighMiB, 29/48 cortical regions of interest (ROIs) (60%) displayed hypoperfusion or ischemia, areas inadequately accessible by LowMiR. These ROIs made up 49% of the 59 ROIs displaying hypoperfusion or ischemia, altogether. Matching of parameters in normal and impaired ROIs between LowMiR and MRI/CT perfusion imaging was significantly poorer than in HighMiB. CONCLUSION: LowMiR using refill-kinetics potentially has the advantage of real time imaging and better resolution. The diagnostic impact, however, proves inferior to HighMiB both with respect to imaging quality and semi-quantitative evaluation.

Assisted Education for Specialized Medicine: A Sustainable Development Plan for Neurosurgery in Myanmar.

BACKGROUND: With only 4 active certified neurosurgeons for a population of 50 million, neurosurgical care was seriously underdeveloped in Myanmar in 2012. Together with the local neurosurgical community, Swiss Neurosurgeons International started a program of assisted education with the aim of increasing the neurosurgical capacity to 60 active neurosurgeons by 2023. METHODS: Our program included a fully sponsored fellowship at an academic hospital in Switzerland for every Myanmar neurosurgeon in training to observe contemporary neurosurgery and the organization of regular workshops, lectures, and educational surgeries in Myanmar. Halfway through the program, we performed a survey to assess its benefits and shortcomings. RESULTS: In 2019, the number of active neurosurgeons in Myanmar had increased to 20, with 50 more in training. Intracranial pressure monitoring, cervical spine surgery, transsphenoidal surgery, and intraoperative electrophysiology have become established procedures. Our survey showed an increased interest by the residents in tumor and vascular surgery and a new interest in spinal surgery. The overall rating of the fellowship was "very good," with language barriers, cultural differences, and coping with inclement weather reported as the greatest difficulties. CONCLUSIONS: Since the start of our project in 2013, a series of contemporary neurosurgical technologies and procedures have been introduced to Myanmar with the help of Swiss Neurosurgeons International. Our survey results have shown the strong points of the ongoing educational program and the weaknesses to be addressed. Midway through our 10-year project, with an expanded and improved education program, our goal of 60 active neurosurgeons in Myanmar by 2023 seems well within reach.