Immersive Photorealistic Three-Dimensional Neurosurgical Anatomy of the Cerebral Arteries: A Photogrammetry-Based Anatomic Study.

BACKGROUND AND OBJECTIVES: Neurosurgeons need a profound knowledge of the surgical anatomy of the cerebral arteries to safely treat patients. This is a challenge because of numerous branches, segments, and tortuosity of the main blood vessels that supply the brain. The objective of this study was to create high-quality three-dimensional (3D) anatomic photorealistic models based on dissections of the brain arterial anatomy and to incorporate this data into a virtual reality (VR) environment. METHODS: Two formaldehyde-fixed heads were used. The vessels were injected with radiopaque material and colored silicone and latex. Before the dissections, the specimens were computed tomography scanned. Stratigraphical anatomic dissection of the neck and brain was performed to present the relevant vascular anatomy. A simplified surface scanning method using a mobile phone-based photogrammetry application was used, and the data were incorporated into a VR 3D modeling software for post-processing and presentation. RESULTS: Fifteen detailed layered photorealistic and two computed tomography angiography-based 3D models were generated. The models allow manipulation in VR environment with sufficient photographic detail to present the structures of interest. Topographical relevant anatomic structures and landmarks were annotated and uploaded for web-viewing and in VR. Despite that the VR application is a dedicated 3D modeling platform, it provided all necessary tools to be suitable for self-VR study and multiplayer scenarios with several participants in one immersive environment. CONCLUSION: Cerebral vascular anatomy presented with photogrammetry surface scanning method allows sufficient detail to present individual vessel's course and even small perforating arteries in photorealistic 3D models. These features, including VR visualization, provide new teaching prospects. The whole study was done with simplified algorithms and free or open-source software platforms allowing creation of 3D databases especially useful in cases with limited body donor-based dissection training availability.

Prognostic value of platelet levels in patients with aneurysmal Subarachnoid Hemorrhage.

Pathophysiological processes following aneurysmal subarachnoid hemorrhage (aSAH) include upregulated underlying systemic inflammation, which is reflected by changes in different peripheral blood cells and their sub-populations. As inflammation is a crucial process that contributes to post-aSAH complications and clincal outcome, blood cell numbers and ratios in systemic circulation may predict the outcome and provide rapid and easy to quantify point of care biomarkers for these critically ill patients. To identify blood-derived cellular inflammatory parameters which allow a precise prediction of patient outcome after aSAH. In this single-center retrospective study, 19 whole blood-derived cellular inflammatory markers and clinical and demographic parameters for 101 aSAH patients were recorded within 24 h after aSAH. Clinical outcome was quantified with modified Rankin scale (mRS) on discharge. Proportional odds logistic regression (POLR) was used to model the patient outcome as the function of clinical parameters and inflammatory markers. The results were validated on a separate hold-out dataset (220 patients). The on-admission platelet count, mean platelet volume (MPV) and mean platelet volume to platelet ratio (MPR) were found to be significant and predictive of patient outcome on discharge. Mean platelet volume (MPV) and mean platelet volume to platelet ratio (MPR) predicted clinical outcome and may serve as easy to quantify point of care biomarker. The findings are potentially relevant for the management of aSAH.

Surgical and endovascular cerebral revascularization for cerebral vasculitis with inflammatory vessel stenosis: a case series.

Autoimmune vasculitides affect the cerebral vasculature significantly in a considerable number of cases. When immunosuppressive treatments fail to prevent stenosis in cerebral vessels, treatment options for affected patients become limited. In this case series, we present four cases of pharmacoresistant vasculitis with recurrent transient ischemic attacks (TIAs) or stroke successfully treated with either extracranial-intracranial (EC-IC) bypass surgery or endovascular stenting. Both rescue treatments were effective and safe in the selected cases. Our experience suggests that cases of pharmacoresistant cerebral vasculitis with recurrent stroke may benefit from rescue revascularization in combination with maximum medical management.

Computer-vision based analysis of the neurosurgical scene - A systematic review.

Introduction: With increasing use of robotic surgical adjuncts, artificial intelligence and augmented reality in neurosurgery, the automated analysis of digital images and videos acquired over various procedures becomes a subject of increased interest. While several computer vision (CV) methods have been developed and implemented for analyzing surgical scenes, few studies have been dedicated to neurosurgery. Research question: In this work, we present a systematic literature review focusing on CV methodologies specifically applied to the analysis of neurosurgical procedures based on intra-operative images and videos. Additionally, we provide recommendations for the future developments of CV models in neurosurgery. Material and methods: We conducted a systematic literature search in multiple databases until January 17, 2023, including Web of Science, PubMed, IEEE Xplore, Embase, and SpringerLink. Results: We identified 17 studies employing CV algorithms on neurosurgical videos/images. The most common applications of CV were tool and neuroanatomical structure detection or characterization, and to a lesser extent, surgical workflow analysis. Convolutional neural networks (CNN) were the most frequently utilized architecture for CV models (65%), demonstrating superior performances in tool detection and segmentation. In particular, mask recurrent-CNN manifested most robust performance outcomes across different modalities. Discussion and conclusion: Our systematic review demonstrates that CV models have been reported that can effectively detect and differentiate tools, surgical phases, neuroanatomical structures, as well as critical events in complex neurosurgical scenes with accuracies above 95%. Automated tool recognition contributes to objective characterization and assessment of surgical performance, with potential applications in neurosurgical training and intra-operative safety management.

Endoscopic endonasal pituitary surgery: How we do it. Consensus statement on behalf of the EANS skull base section.

Introduction and research question: The use of an endoscope in skull base surgery provides a panoramic close-up view over the intracranial structures from multiple angles with excellent illumination, thus permitting greater extent of resection of tumors arising at sellar area, mostly represented by PitNet - Pituitary neuroendocrine tumors, with higher likelihood of preserving vital/intact gland tissue. For this refined specialty of neurosurgery, unique skills need to be acquired along a steep learning curve. Material and methods: EANS (European Association of Neurosurgical Societies) skull base section panelists were enrolled and 11 completed the survey: the goal was to provide a consensus statement of the endoscopic endonasal approach for pituitary adenoma surgery. Results: The survey consisted of 44 questions covering demographics data (i.e., academic/non-academic center, case load, years of experience), surgical techniques (i.e., use of neuronavigation, preoperative imaging), and follow-up management. Discussion and conclusions: In this paper we identified a series of tips and tricks at different phases of an endoscopic endonasal pituitary surgery procedure to underline the crucial steps to perform successful surgery and reduce complications: we took in consideration the principles of the surgical technique, the knowledge of the anatomy and its variations, and finally the importance of adjoining specialties experts.

mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells.

The cardiovascular risk factors, including smoking, ethanol, and oxidative stress, can induce cellular senescence. The senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase (MMPs). These pro-inflammatory molecules and MMPs promote the infiltration and accumulation of inflammatory cells in the vascular tissue, exacerbating vascular tissue inflammation. MMPs damage vascular tissue by degenerating the extracellular matrix. Consequently, these cellular and molecular events promote the initiation and progression of cardiovascular diseases. We used Rapalink-1, an mTOR inhibitor, to block ethanol-induced senescence. Rapalink-1 inhibited oxidative-stress-induced DNA damage and senescence in endothelial cells exposed to ethanol. It attenuated the relative protein expression of senescence marker P21 and improved the relative protein expression of DNA repair protein KU70 and aging marker Lamin B1. It inhibited the activation of NF-κB, MAPKs (P38 and ERK), and mTOR pathway proteins (mTOR, 4EBP-1, and S6). Moreover, Rapalink-1 suppressed ethanol-induced mRNA expression of ICAM-1, E-selectin, MCP-1, IL-8, MMP-2, and TIMP-2. Rapalink-1 also reduced the relative protein expression of MMP-2. In summary, Rapalink-1 prevented senescence, inhibited pro-inflammatory pathway activation, and ameliorated pro-inflammatory molecule expression and MMP-2.

Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases.

BACKGROUND: Smoking, alcohol abuse, and hypertension are - among others, potential risk factors for cardiovascular diseases. These risk factors generate oxidative stress and cause oxidative stress-induced DNA damage, resulting in cellular senescence and senescence-associated secretory phenotype (SASP). The SASP factors in feed-forward response exacerbate inflammation and cause tissue remodeling, resulting in atherosclerotic plaque formation and rupture. RESULTS: Colchicine inhibited ROS generation and mitigated oxidative stress-induced DNA damage. It dampened oxidative stress-induced endothelial cell senescence and improved the expression of DNA repair protein KU80 and aging marker Lamin B1. The drug attenuated the expression of senescence marker P21 at mRNA and protein levels. The pathway analysis showed that colchicine inhibited NF-κB and MAPKs pathways and subdued mTOR activation. Colchicine also attenuated mRNA expression of interleukin (IL)-1ß, IL-6, IL-8, MCP-1, ICAM-1, and E-selectin. Furthermore, colchicine reduced the mRNA and protein expression of matrix metalloproteinase (MMP-2). CONCLUSION: In summary, colchicine blocked oxidative stress-induced senescence and SASP by inhibiting the activation of NF-κB and MAPKs pathways.

The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review.

Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture. After a systematic search, abstract screening, and full-text screening, 30 research articles were included in the review. In this systematic review, we summarized the scientific literature reporting findings on NF-κB's role in the pathogenesis of IAs. In conclusion, the activation of the NF-κB pathway was associated with IA formation, progression, and rupture.

Differences in intraoperative sampling during meningioma surgery regarding CNS invasion - Results of a survey on behalf of the EANS skull base section.

Introduction: and Research Question: Invasive growth of meningiomas into CNS tissue is rare but of prognostic significance. While it has entered the WHO classification as a stand-alone criterion for atypia, its true prognostic impact remains controversial. Retrospective analyses, on which the current evidence is based, show conflicting results. Discordant findings might be explained by different intraoperative sampling methodologies. Material and methods: To assess the applied sampling methods in the light of the novel prognostic impact of CNS invasion, an anonymous survey was designed and distributed via the EANS website and newsletter. The survey was open from June 5th until July 15th, 2022. Results: After exclusion of 13 incomplete responses, 142 (91.6%) datasets were used for statistical analysis. Only 47.2% of participants' institutions utilize a standardized sampling method, and 54.9% pursue a complete sampling of the area of contact between the meningioma surface and CNS tissue. Most respondents (77.5%) did not change their sampling practice after introduction of the new grading criteria to the WHO classification of 2016. Intraoperative suspicion of CNS invasion changes the sampling for half of the participants (49.3%). Additional sampling of suspicious areas of interest is reported in 53.5%. Dural attachment and adjacent bone are more readily sampled separately if tumor invasion is suspected (72.5% and 74.6%, respectively), compared to meningioma tissue with signs of CNS invasion (59.9%). Discussion and conclusions: Intraoperative sampling methods during meningioma resection vary among neurosurgical departments. There is need for a structured sampling to optimize the diagnostic yield of CNS invasion.

Colchicine Protects against Ethanol-Induced Senescence and Senescence-Associated Secretory Phenotype in Endothelial Cells.

Inflammaging is a potential risk factor for cardiovascular diseases. It results in the development of thrombosis and atherosclerosis. The accumulation of senescent cells in vessels causes vascular inflammaging and contributes to plaque formation and rupture. In addition to being an acquired risk factor for cardiovascular diseases, ethanol can induce inflammation and senescence, both of which have been implicated in cardiovascular diseases. In the current study, we used colchicine to abate the cellular damaging effects of ethanol on endothelial cells. Colchicine prevented senescence and averted oxidative stress in endothelial cells exposed to ethanol. It lowered the relative protein expression of aging and senescence marker P21 and restored expression of the DNA repair proteins KU70/KU80. Colchicine inhibited the activation of nuclear factor kappa B (NFκ-B) and mitogen activated protein kinases (MAPKs) in ethanol-treated endothelial cells. It reduced ethanol-induced senescence-associated secretory phenotype. In summary, we show that colchicine ameliorated the ethanol-caused molecular events, resulting in attenuated senescence and senescence-associated secretory phenotype in endothelial cells.

SARS-CoV-2 infection increases risk of intracranial hemorrhage.

Introduction: SARS-CoV-2 virus infection causes a dysbalanced and severe inflammatory response, including hypercytokinemia and immunodepression. Systemic inflammation triggered by a viral infection can potentially cause vascular damage, which may lead to cardiovascular and neurovascular events. Research question: The aim was to investigate whether CNS complications are related to COVID-19. Materials and methods: We examined 21 patients suffering from stroke and intracranial hemorrhage (ICH) and 9 (43%) of them were male. We compared relative frequencies using Fisher's exact test. As we had few observations and many variables, we used principal component analysis (PCA) to reduce data dimensionality. We trained a linear support vector machine (SVM) on the first two PCs of the laboratory data to predict COVID-19. Results: Patients suffering from stroke had either hypertension or SARS-CoV-2 infection, but seldom both (OR = 0.05, p = 0.0075). The presence of SARS-CoV-2 infection was strongly associated with the logarithm of CRP (p = 1.4e-07) and with D-DIMER (p = 1.6e-05) and moderately with PT (p = 0.0024). SARS-CoV-2 infection was not related to any other factor. CRP, D-DIMER, PT, and INR were all related to each other (R 2 ranging from 0.19 to 0.52, p ranging from 0.012 to < 0.0001). The first two PCs covered 96% of the variance in the four variables. Using them, perfect linear discrimination between patients suffering from COVID-19 and other patients could be achieved. Discussion and conclusion: SARS-CoV-2 infection causes systemic inflammation, which is suggested as a predictor of the severe course of ICH. SARS-CoV-2 infection is an additional risk factor for vascular complications.

Meta-review on Perforation Model of Subarachnoid Hemorrhage in Mice: Filament Material as a Possible Moderator of Mortality.

Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databases PubMed, Embase, and Web of Science for articles describing in vivo experiments using the SAH perforation mouse model and measuring mortality, SAH grade, and/or vasospasm. After screening, 42 articles (total of 1964 mice) were included into systematic review and meta-analysis. Certain model characteristics were insufficiently reported, e.g., perforation location (not reported in six articles), filament (material (n = 15) and tip texture (n = 25)), mouse age (n = 14), and weight (n = 10). Used injective anesthetics and location of perforation showed large variation. In a random-effects meta-analysis, the overall animal mortality following SAH was 21.3% [95% CI: 17.5%, 25.7%] and increased with longer observational periods. Filament material significantly correlated with animal mortality (p = 0.024) after exclusion of hyperacute studies (time after SAH induction < 24 h). Reported mean SAH grade was 10.7 [9.6, 11.7] on the scale of Sugawara (J Neurosci Methods 167:327-34, 2008). Furthermore, mean diameter of large cerebral arteries after SAH was reduced by 27.6% compared to sham-operated non-SAH mice. Uniforming standards of experimental procedures and their reporting are indispensable to increase overall comparability.

Update in Cushing disease: What the neurosurgeon has to KNOW, on behalf of the EANS skull base section.

Introduction: Cushing's disease is a state of chronic and excessive cortisol levels caused by a pituitary adenoma. Research question: CD is a complex entity and often entails difficulties in its diagnosis and management. For that reason, there are still controversial points to that respect. The aim of this consensus paper of the skull base section of the EANS is to review the main aspects of the disease a neurosurgeon has to know and also to offer updated recommendations on the controversial aspects of its management. Material and methods: PUBMED database was used to search the most pertinent articles published on the last 5 years related with the management of CD. A summary of literature evidence was proposed for discussion within the EANS skull base section and other international experts. Results: This article represents the consensual opinion of the task force regarding optimal management and surgical strategy in CD. Discussion and conclusion: After discussion in the group several recommendations and suggestions were elaborated. Patients should be treated by an experienced multidisciplinary team. Accurate clinical, biochemical and radiological diagnosis is mandatory. The goal of treatment is the complete adenoma resection to achieve permanent remission. If this is not possible, the treatment aims to achieving eucortisolism. Radiation therapy is recommended to patients with CD when surgical options have been exhausted. All patients in remission should be tested all life-long.

Intracranial Aneurysm Rupture after SARS-CoV2 Infection: Case Report and Review of Literature.

BACKGROUND: SARS-CoV virus infection results in a dysbalanced and severe inflammatory response with hypercytokinemia and immunodepression. Viral infection triggers systemic inflammation and the virus itself can potentially cause vascular damage, including blood-brain barrier (BBB) disruption and alterations in the coagulation system, which may result in cardiovascular and neurovascular events. Here, we review the literature and present a case of COVID-19 infection leading to an aneurysmal subarachnoid haemorrhage (aSAH). CASE DESCRIPTION: A 61-year-old woman presented with dyspnea, cough, and fever. She had a history of hypertension and was overweight with a body mass-index of 34. There was no history of subarachnoid hemorrhage in the family. Due to low oxygen saturation (89%) she was admitted into ICU. A chest CT showed a typical picture of COVID-19 pneumonia. The PCR-based test of an oropharyngeal swab was COVID-19-positive. In addition to oxygen support she was prescribed with favipiravir and hydroxychloroquine. She experienced a sudden headache and lost consciousness on the second day. Computer tomography (CT) with CT-angiography revealed a subarachnoid haemorrhage in the basal cisterns from a ruptured anterior communicating artery aneurysm. The aneurysm was clipped microsurgically through a left-sided standard pterional approach and the patient was admitted again to the intensive care unit for further intensive medical treatment. Post-operatively, the patient showed slight motor dysphasia. No other neurological deficits. CONCLUSION: Systemic inflammation and ventilator support-associated blood pressure fluctuations may trigger aneurysmal subarachnoid haemorrhage secondary to COVID-19 infection. COVID-19 infection could be considered as one of the possible risk factors leading to instability and rupture of intracranial aneurysm.

Olfactory Groove Meningiomas: Comprehensive assessment between the different microsurgical transcranial approaches and the Endoscopic Endonasal Approaches, systematic review and metanalysis on behalf of the EANS skull base section.

•OGM surgery is much more complex than a simple debate of "from above or from below" (transcranial vs endoscopic).•Lateral Sub-frontal and Superior Interhemispheric seem the most effective, superior and versatile approaches for OGM.•Minimally Invasive Transcranial approaches showed no inferiority in OGM sized <4 â€‹cm.•Endoscopic Endonasal Approaches showed inferior results in surgical and in functional outcomes for OGM.

Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section.

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach. The new terminology "Pituitary neuroendocrine tumors" (PitNet) that was recently proposed to replace "pituitary adenomas" reflects this change of paradigm. In this narrative review, we aim to provide a state of the art of actual knowledge, controversies, and recommendations in the management of APT. We propose an overview of current prognostic markers, including the recent five-tiered clinicopathological classification. We further establish and discuss the following recommendations from a neurosurgical perspective: (i) surgery and multi-staged surgeries (without or with parasellar resection in symptomatic patients) should be discussed at each stage of the disease, because it may potentialize adjuvant medical therapies; (ii) temozolomide is effective in most patients, although 30% of patients are non-responders and the optimal timeline to initiate and interrupt this treatment remains questionable; (iii) some patients with selected clinicopathological profiles may benefit from an earlier local radiotherapy and/or chemotherapy; (iv) novel therapies such as VEGF-targeted therapies and anti-CTLA-4/anti-PD1 immunotherapies are promising and should be discussed as 2nd or 3rd line of treatment. Finally, whether neurosurgeons have to operate on "pituitary adenomas" or "PitNets," their role and expertise remain crucial at each stage of the disease, prompting our community to deal with evolving concepts and therapeutic resources.

Ciprofloxacin enhances phototoxicity of 5-aminolevulinic acid mediated photodynamic treatment for chordoma cell lines.

BACKGROUND: Chordoma are uncommon aggressive tumors of the skeleton. Surgical resection is often subtotal and adjuvant treatment possibilities are limited as chordomas are highly chemo- and radioresistant. In the present study we examined the impact of 5-ALA PDT on different human chordoma cell lines. Furthermore, we investigated the variation of two parameters: (1.) 5-ALA incubation time and (2.) supplemental use of ciprofloxacin as iron chelator. METHODS: Experiments were realized in vitro with three different human chordoma cell lines: U-CH2, U-CH2B and U-CH14. After pre-incubation for 24 h with various concentrations of ciprofloxacin (1.5 - 5.0 µg/ml), different amounts of 5-ALA (15 - 50 µg/ml) were applied to the cells either for a brief (4 h) or a long (6 h) incubation time. Subsequently cells were exposed to photodynamic radiation. Cell viability was exploited by WST-1 assay. Thus, for each of the three cell lines, two drug combinations (ciprofloxacin plus 5-ALA and 5-ALA only) and two incubation times (short, 4 h and long, 6 h) were tested. Negative control groups were also examined. RESULTS: Supplemental use of ciprofloxacin led to increased cell death in each of the cell lines. Different 5-ALA incubation times (4 h vs. 6 h) showed no significant differences in cell viability except for U-CH2. CONCLUSION: Ciprofloxacin as an ordinary applied antibiotic, enhanced the effect of 5-ALA PDT on different human chordoma cell lines in vitro. The impact was dependent on the dose of ciprofloxacin-5-ALA. There were no notable differences for the tested 5-ALA incubation times. In human chordoma cell lines 5-ALA PDT may effectively be amended by ciprofloxacin.

Quantification of PpIX-fluorescence of cerebral metastases: a pilot study.

5-ALA fluorescence-guided surgery (FGS) is a major advance in neuro-oncological surgery. So far, Protoporphyrin IX (PpIX)-fluorescence has been observed in about half of cerebral metastases resected with routinely equipped microscopes during 5-ALA FGS. The aim of the present pilot study was to quantify PpIX-induced fluorescence of cerebral metastases with a spectrometer. We hypothesize that non-fluorescing metastases under the operating microscope may have spectrometrically measurable levels of fluorescence. A second aim was to analyze correlations between quantified 5-ALA fluorescence and histology or primary tumor type, respectively. Standard FGS was performed in all patients. The fluorescence intensity of the metastasis was semi-quantitatively determined in vivo by a senior surgeon using a special surgical microscope equipped for FGS. A systematic spectrometric ex vivo evaluation of tumor specimens and PpIX-induced fluorescence was performed using a spectrometer connected by optic fibers to a handheld probe. Quantification of 5-ALA-derived fluorescence was measured in a standardized manner with direct contact between mini-spectrometer and metastasis. The difference between the maximum PpIX-fluorescence at 635 nm and the baseline fluorescence was defined as the PpIX fluorescence intensity of the metastasis and given in arbitrary units (AU). Diagnosis of a cerebral metastasis was confirmed by histopathological analysis. A total of 29 patients with cerebral metastases were included. According to neuropathological analysis, 11 patients suffered from non-small cell lung cancer, 10 patients from breast cancer, 6 patients from cancer originating in the gastro-intestinal tract, 1 patient suffered from a malignant melanoma and one patient from renal cancer. The mean age was 63 years (37-81 years). 15 patients were female, 14 patients male. 13 cerebral metastases were considered as ALA-positive by the surgeon. In nine metastases, 5-ALA fluorescence was not visible to the naked eye and could only be detected using the spectrometer. The threshold for an ALA signal rated as "positive" by the surgeon was PpIX fluorescence above 1.1 × 106 AU. The mean PpIX fluorescence of all analyzed cerebral metastases was 1.29 × 106 ± 0.23 × 106 AU. After quantification, we observed a significant difference between the mean 5-ALA-derived fluorescence in NSCLC and breast cancer metastases (Mean Diff: - 1.2 × 106; 95% CI of difference: - 2.2 × 106 to - 0.15 × 106; Sidák-adjusted p = 0.026). In our present pilot series, about half of cerebral metastases showed a 5-ALA fluorescence invisible to the naked eye. Over 50% of these non-fluorescent metastases show a residual 5-ALA fluorescence which can be detected and quantified using a spectrometer. Moreover, the quantified 5-ALA signal significantly differed with respect to the primary tumor of the corresponding cerebral metastasis. Further studies should evaluate the predictive value of the 5-ALA signal and if a quantified 5-ALA signal enables a reliable intraoperative differentiation between residual tumor tissue and edematous brain-in particular in metastases with a residual fluorescence signal invisible to the naked eye.

Is the Intensity of 5-Aminolevulinic Acid-Derived Fluorescence Related to the Light Source?

OBJECTIVE: With the introduction of the 5-aminolevulinic acid (5-ALA) technique, surgical neuro-oncology has made a major advance. 5-ALA fluorescence-guided resection of malignant glioma results in more complete surgical resections and subsequently prolonged survival. However, it remains uncertain how light intensities of the blue light source and 5-ALA-derived fluorescence intensities of the illuminated tissue are connected. The aim of the present study was to compare light intensities of different blue light sources and protoporphyrin (PpIX) fluorescence intensities of PpIX solutions with defined concentrations after illumination with different light sources. MATERIAL AND METHODS: The light spectrum of 7 different blue light sources and the fluorescence intensity of 2 PpIX solutions (0.15 µg/mL and 5 µg/mL) were quantified after illumination. We compared the Zeiss OPMI Pentero microscope, the Zeiss OPMI Pentero 900 microscope, the Leica M530 OH6 microscope, an endoscope equipped with the 5-ALA technique, a mini-spectrometer equipped with a multi-channel light-emitting diode (LED) source emitting monochromatic light, a modified commercially available LED head lamp, and a commercially available unmodified UV-LED lamp. PpIX fluorescence was quantified in a standardized setup using a mini-spectrometer. RESULTS: Maximum light intensities of the evaluated light sources were reached at different wavelengths. All tested devices were able to detect PpIX-induced fluorescence. However, the intensity of PpIX fluorescence of the differently concentrated PpIX solutions (0.15 µg/mL and 5 µg/mL) was significantly dependent on the light source used. CONCLUSIONS: Intensity of the 5-ALA-derived fluorescence is related to the light source used.