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

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

5-ALA complete resections go beyond MR contrast enhancement: shift corrected volumetric analysis of the extent of resection in surgery for glioblastoma

Background: The technique of 5-aminolevulinic acid (5-ALA) tumor fluorescence is increasingly used to improve visualization of tumor tissue and thereby to increase the rate of patients with gross total resections. In this study, we measured the resection volumes in patients who underwent 5-ALA-guided surgery for non-eloquent glioblastoma and compared them with the preoperative tumor volume. Methods: We selected 13 patients who had received a complete resection according to intraoperative 5-ALA induced fluorescence and CRET according to post-operative T1 contrast-enhanced MRI. The volumes of pre-operative contrast enhancing tissue, post-operative resection cavity and resected tissue were determined through shift-corrected volumetric analysis. Results: The mean resection cavity (29cm3) was marginally smaller than the pre-operative contrast-enhancing tumor (39cm3, p = 0.32). However, the mean overall resection volume (84cm3) was significantly larger than the pre-operative contrast-enhancing tumor (39cm3, p = 0.0087). This yields a mean volume of resected 5-ALA positive, but radiological non-enhancing tissue of 45cm3. The mean calculated rim of resected tissue surpassed pre-operative tumor diameter by 6mm (range 0-10mm). Conclusions: Results of the current study imply that (i) the resection cavity underestimates the volume of resected tissue and (ii) 5-ALA complete resections go significantly beyond the volume of pre-operative contrast-enhancing tumor bulk on MRI, indicating that 5-ALA also stains MRI non-enhancing tumor tissue. Use of 5-ALA may thus enable extension of coalescent tumor resection beyond radiologically evident tumor. The impact of this more extended resection method on time to progression and overall survival has not been determined, and potentially puts adjacent and functionally intact tissue at risk

ACE-inhibitors: a preventive measure for bone flap resorption after autologous cranioplasty?

OBJECTIVEDecompressive craniectomy (DC) is an established treatment for refractory intracranial hypertension. It is usually followed by autologous cranioplasty (AC), the reinsertion of a patient's explanted bone flap. A frequent long-term complication of AC is bone flap resorption (BFR), which results in disfigurement as well as loss of the protective covering of the brain. This study investigates risk factors for BFR after AC, including medical conditions and antihypertensive drug therapies, with a focus on angiotensin-converting enzyme inhibitors (ACEIs), which have been associated with a beneficial effect on bone healing and bone preservation in orthopedic, osteoporosis, and endocrinology research.METHODSIn this single-center, retrospective study 183 consecutive cases were evaluated for bone flap resorption after AC. Information on patient demographics, medical conditions, antihypertensive therapy, and BFR-defined as an indication for revision surgery established by a neurosurgeon based on clinical or radiographic assessments-was collected. A Kaplan-Meier analysis of time from AC to diagnosis of BFR was performed, and factors associated with BFR were investigated using the log-rank test and Cox regression.RESULTSA total of 158 patients were considered eligible for inclusion in the data analysis. The median follow-up time for this group was 2.2 years (95% CI 1.9-2.5 years). BFR occurred in 47 patients (29.7%), with a median time to event of 3.7 years (95% CI 3.3-4.1 years). An ACEI prescription was recorded in 57 cases (36.1%). Univariate Kaplan-Meier analysis and the log-rank test revealed that ACEI therapy (2-year event free probability [EFP] 83.8% ± 6.1% standard error vs 63.9% ± 5.6%, p = 0.02) and ventriculoperitoneal (VP) shunt treatment (2-year EFP 86.9% ± 7.1% vs 66% ± 5.0%, p = 0.024) were associated with a lower probability of BFR. Multiple Cox regression analysis showed ACEI therapy (HR 0.29, p = 0.012), VP shunt treatment (HR 0.278, p = 0.009), and male sex (HR 0.500, p = 0.040) to be associated with a lower risk for BFR, whereas bone fragmentation (HR 1.92, p = 0.031) was associated with a higher risk for BFR.CONCLUSIONSHypertensive patients treated with ACEIs demonstrate a lower rate of BFR than patients treated with other hypertensive medications and nonhypertensive patients. Our results are in line with previous reports on the positive influence of ACEIs on bone healing and preservation. Further analysis of the association between ACEI treatment and BFR development is needed and will be evaluated in a multicenter prospective trial

Intraoperative fabrication of patient-specific moulded implants for skull reconstruction: single-centre experience of 28 cases

Background: Intraoperatively fabricated polymethylmethacrylate (PMMA) implants based on computer-designed moulds were used to improve cosmetic results after hard tissue replacement. To assess the implant's cosmetic and functional results we performed both subjective and objective assessments. Methods: This retrospective analysis was performed using a cohort of 28 patients who received PMMA implants between February 2009 and March 2012. The cosmetic and functional results were assessed using a patient questionnaire. Furthermore an objective volumetric subtraction score (0-100) was applied and implant thickness, as well as gaps and tiers, were measured. Results: Patients mainly judged their cosmetic result as "good”. Two of the 28 patients found their cosmetic result unfavourable. The functional result and stability was mainly judged to be good. Measurements of implant thickness showed a very high correlation with the thickness of the contralateral bone. Volumetric subtraction led to a median quality of 80 on a scale from 0 to 100. Median gaps around the margins of the implant were 1.5mm parietally, 1.7mm frontally and 3.5mm fronto-orbitally, and median tiers were 1.2mm, 0mm and 0mm respectively. The overall rate of surgical revisions was 10.7% (three patients). Two patients suffered from wound healing disturbances (7.1%). The overall complication rate was comparable to other reports in the literature. Conclusions: Implantation of intraoperatively fabricated patient-specific moulded implants is a cost-effective and safe technique leading to good clinical results with a low complication rate

What happens to the bone flap? Long-term outcome after reimplantation of cryoconserved bone flaps in a consecutive series of 92 patients.

BACKGROUND Reimplantation of cryoconserved autologous bone flaps is a standard procedure after decompressive craniotomies. Aseptic necrosis and resorption are the most frequent complications of this procedure. At present there is no consensus regarding the definition of the relevant extent and indication for surgical revision. The objective of this retrospective analysis was to identify the incidence of bone flap resorption and the optimal duration of follow-up. METHODS Between February 2009 and March 2012, 100 cryoconserved autologous bone flaps were reimplanted at the Department of Neurosurgery, Inselspital Bern. Three patients were not available for follow-up, and five patients died before follow-up. All patients underwent follow-up at 6 weeks and a second follow-up more than 12 months postoperatively. A clinical and CT-based score was developed for judgment of relevance and decision making for surgical revision. RESULTS Mean follow-up period was 21.6 months postoperatively (range: 12 to 47 months); 48.9 % (45/92) of patients showed no signs of bone flap resorption, 20.7 % (19/92) showed minor resorption with no need for surgical revision, and 30.4 % (28/92) showed major resorption (in 4 % of these the bone flap was unstable or collapsed). CONCLUSIONS Aseptic necrosis and resorption of reimplanted autologous bone flaps occurred more frequently in our series of patients than in most reports in the literature. Most cases were identified between 6 and 12 months postoperatively. Clinical observation or CT scans of patients with autologous bone flaps are recommended for at least 12 months. Patient-specific implants may be preferable to autologous bone flaps

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

Optimal Combinations of Chemotherapy and Radiotherapy in Low-Grade Gliomas: A Mathematical Approach.

Low-grade gliomas (LGGs) are brain tumors characterized by their slow growth and infiltrative nature. Treatment options for these tumors are surgery, radiation therapy and chemotherapy. The optimal use of radiation therapy and chemotherapy is still under study. In this paper, we construct a mathematical model of LGG response to combinations of chemotherapy, specifically to the alkylating agent temozolomide and radiation therapy. Patient-specific parameters were obtained from longitudinal imaging data of the response of real LGG patients. Computer simulations showed that concurrent cycles of radiation therapy and temozolomide could provide the best therapeutic efficacy in-silico for the patients included in the study. The patient cohort was extended computationally to a set of 3000 virtual patients. This virtual cohort was subject to an in-silico trial in which matching the doses of radiotherapy to those of temozolomide in the first five days of each cycle improved overall survival over concomitant radio-chemotherapy according to RTOG 0424. Thus, the proposed treatment schedule could be investigated in a clinical setting to improve combination treatments in LGGs with substantial survival benefits

What happens to the bone flap? Long-term outcome after reimplantation of cryoconserved bone flaps in a consecutive series of 92 patients

Background: Reimplantation of cryoconserved autologous bone flaps is a standard procedure after decompressive craniotomies. Aseptic necrosis and resorption are the most frequent complications of this procedure. At present there is no consensus regarding the definition of the relevant extent and indication for surgical revision. The objective of this retrospective analysis was to identify the incidence of bone flap resorption and the optimal duration of follow-up. Methods: Between February 2009 and March 2012, 100 cryoconserved autologous bone flaps were reimplanted at the Department of Neurosurgery, Inselspital Bern. Three patients were not available for follow-up, and five patients died before follow-up. All patients underwent follow-up at 6weeks and a second follow-up more than 12months postoperatively. A clinical and CT-based score was developed for judgment of relevance and decision making for surgical revision. Results: Mean follow-up period was 21.6months postoperatively (range: 12 to 47months); 48.9% (45/92) of patients showed no signs of bone flap resorption, 20.7% (19/92) showed minor resorption with no need for surgical revision, and 30.4% (28/92) showed major resorption (in 4% of these the bone flap was unstable or collapsed). Conclusions: Aseptic necrosis and resorption of reimplanted autologous bone flaps occurred more frequently in our series of patients than in most reports in the literature. Most cases were identified between 6 and 12months postoperatively. Clinical observation or CT scans of patients with autologous bone flaps are recommended for at least 12months. Patient-specific implants may be preferable to autologous bone flaps

Polymorphous oligodendroglioma of Zülch revisited: a genetically heterogeneous group of anaplastic gliomas including tumors of bona fide oligodendroglial differentiation.

A polymorphous variant of oligodendroglioma was described by K.J. Zülch half a century ago, and is only very sporadically referred to in the subsequent literature. In particular, no comprehensive analysis with respect to clinical or genetic features of these tumors is available. From a current perspective, the term polymorphous oligodendroglioma (pO) may appear as contradictory in terms, as nuclear monotony is a histomorphological hallmark of oligodendrogliomas. For the purpose of this study, we defined pO as diffusely infiltrating gliomas felt to be of oligodendroglial rather than astrocytic differentiation and characterized by the presence of multinucleate tumor giant cells and/or nuclear pleomorphism. In a total of nine patients, we identified tumors consistent with this working definition. All tumors were high-grade. We characterized these with respect to clinical, histomorphological and genetic features. Despite clinical and genetic heterogeneity, we identified a subset of tumors of bona fide oligodendroglial differentiation as characterized by combined loss of heterozygosity of chromosome arms 1p and 19q (LOH 1p19q). Those tumors that lacked LOH 1p19q showed a high frequency of IDH1 mutations and loss of alpha thalassemia/mental retardation syndrome X-linked gene (ATRX) immunoreactivity, indicating a possible phenotypic convergence of true oligodendrogliomas and gliomas of the alternative lengthening of telomeres (ALT) pathway. p53 alterations were common irrespective of the 1p19q status. Histomorphologically, the tumors featured interspersed bizarre multinucleate giant tumor cells, while the background population varied from monotonous to significantly pleomorphic. Our findings indicate, that a rare polymorphous - or "giant cell" - variant of oligodendroglioma does indeed exist