Among Central Nervous System (CNS) tumors, diffuse glioma are the most infiltrating and malignant tumors. According to the World Health Organization (WHO), they are classified into different grades, referring to their pathological class and histological properties. To treat glioma tumors, many methods have been proposed, still the standard one remains the maximal safe total resection. During the operation, many difficulties obstruct the surgeon to identify the infiltrated areas, which contains diffuse tumors cells, around the solid area of the tumor, overlapping the healthy areas, and presenting the same visual appearances. If not totally removed, these infiltrating zones can increase the risk of recurrence and affects the survival rate of patient. To overcome this problem, we develop a multimodal two-photon endomicroscope, based on the endogenous fluorescence of brain tissues, to assist the surgeon during the surgery. The tool will provide him information on the infiltrated areas and their histological nature. In this paper, we tried to discriminate between metastasis, low grade and high grade glioma from healthy fresh tissues, presenting a multimodal study using deep ultraviolet, visible and near infrared excitation to acquire spectral measurements, Fluorescence Lifetime Imaging (FLIM) and Two-Photon Emission Fluorescence (TPEF) imaging. We compared also our TPEF and FLIM images to the histological images.

Background. - To report on the outcome of patients diagnosed with central nervous system haemangiopericytoma (HPC) or solitary fibrous tumours (SFT) and identify factors that may influence recurrence and survival. Material and methods. - Between January 1977 and December 2016, a retrospective search identified 22 HPCs/SFTs. The patients underwent a total of 40 surgical resections and 63.6% received radiotherapy. Median follow-up was 7.8 years. Results. - Six patients (27.3%) were re-operated for tumour recurrence. At the end of the study, 15 patients (68.2%) had no residual tumour on the last imaging. Surgical recurrence-free survival at 5 years was 77.4%, [95% CI: 60.1-99.8]. None of the investigated variables was associated with recurrence. At the end of the study, 5 patients were deceased (22.7%) and only 10 patients (45.5%) had no residual tumour on the last imaging and were alive. Overall survival at 5 years was 95%, [95% CI: 85.9-100]. None of the investigated variables was associated with overall survival. Patients who received radiotherapy demonstrated neither a reduced risk of surgical recurrence (P = 0.378) nor a longer overall survival (P = 0.405). Conclusion. - SFTs/HPCs are associated with a significant risk of recurrence that may reduce the survival. Even if we could not demonstrate their benefit in this limited series, we believe that tailored maximal tumour resection on initial surgery is beneficial and that adjuvant RT is useful for tumours displaying grade II or III, even in case of complete removal. (C) 2017 Elsevier Masson SAS. All rights reserved.

Introduction. - Malignant primary diffuse leptomeningeal gliomatosis (MPDLG) are rare central nervous system neoplasms associated with a poor outcome. Case report. - We report the case of a 40-year-old woman who presented with unusual worsening of bilateral sciatica, headaches, diplopia and a left proptosis. MRI of the head and spine showed multiple leptomeningeal lesions with no intra parenchymal involvement. The search for a primary tumor was negative. An open surgical biopsy of the prominent intradural lumbar tumor was performed within a week. Histopathology, immunochemistry and molecular analyses revealed a malignant glioma with histone H3.3 K27M mutation. The patient was referred to the neuro-oncologist for chemotherapy and craniospinal radiotherapy. Despite aggressive therapy, she died of disseminated tumoral progression, 18 weeks after the diagnosis. Conclusion. - MPLG is a rare tumor which should be considered whenever a patient presents with diffuse or multinodular meningeal contrast-enhancing lesions. Some cases of MLPG share histological and immunophenotypical features with diffuse midline gliomas H3-K27M-mutant, a rapidly fatal disease. The diagnosis remains histopathological and, therefore a biopsy is obligatory without delay. Immunohistochemistry and/or molecular analyses are now currently essential for a formal classification and, to provide a better prediction of clinical outcome, particularly in this heterogeneous group of tumors. (C) 2018 Elsevier Masson SAS. All rights reserved.

Until today the endogenous fluorescence of tissue were neglected and often consider as a source of noise in medical imaging, however recent work and future technologies seems to reconsider it as a new imaging modality in medical devices. One of the precursor fields for the use of autofluorescenceAutofluorescence in tissue is the study of cancerology, which was recognized as a powerful tool for the future of medical devices. Although many studies have been started and done in this field, there are still numerous aspects of the signal that are not well known yet such as time dependence after extraction of fresh tissues. In this work, freshly resected human samples were exanimated in order to investigate their autofluorescence changes with time. Primary results of this examination prove that fluorescence intensity and lifetime values of healthy and tumoral samples decreased slightly with time.

Accurate intraoperative tumour margin assessment is a major challenge in neurooncology, where sparse tumours beyond the bulk tumour are left undetected under conventional resection. Non-linear optical imaging can diagnose tissue at the sub-micron level and provide functional label-free histopathology in vivo . For this reason, a non-linear endomicroscope is being developed to characterize brain tissue intraoperatively based on multiple endogenous optical contrasts such as spectrally- and temporally-resolved fluorescence. To produce highly sensitive optical signatures that are specific to a given tissue type, short femtosecond pulsed lasers are required for efficient two-photon excitation. Yet, the potential of causing bio-damage has not been studied on neuronal tissue. Therefore, as a prerequisite to clinically testing the non-linear endomicroscope in vivo , the effect of short laser pulse durations (40–340 fs) on ex vivo brain tissue was investigated by monitoring the intensity, the spectral, and the lifetime properties of endogenous fluorophores under 800 and 890 nm two-photon excitation using a bi-modal non-linear endoscope. These properties were also validated by imaging samples on a benchtop multiphoton microscope. Our results show that under a constant mean laser power, excitation pulses as short as 40 fs do not negatively alter the biochemical/ biophysical properties of tissue even for prolonged irradiation.

A key challenge of central nervous system tumor surgery is to discriminate between brain regions infiltrated by tumor cells and surrounding healthy tissue. Although monitoring of autofluorescence could potentially be an efficient way to provide reliable information for these regions, we found little information on this subject, and thus we conducted studies of brain tissue optical properties. This particular study focuses on the different optical quantitative responses of human central nervous system tumors and their corresponding controls. Measurements were performed on different fixed human tumoral and healthy brain samples. Four groups of central nervous system tumors (glioblastoma, diffuse glioma, meningioma and metastasis) were discriminated from healthy brain and meninx control tissues. A threshold value was found for the scattering and absorption coefficient between tumoral and healthy groups. Emission Spectra of healthy tissue had a significant higher intensity than tumoral groups. The redox and optical index ratio were thenn calculated and these also showed significant discrimination. Two fluorescent molecules, NADH and porphyrins, showed distinct lifetim values among the different groups of samples. This study defines several optical indexes that can act as combinated indicators to discriminate healthy from tumoral tissues.

Introduction. - Dysembryoplastic neuroepithelial tumors and gangliogliomas are developmental glioneuronal tumors usually revealed by partial epilepsy. High epileptogenicity, childhood epilepsy onset, drug-resistance, temporal location, and seizure freedom after complete resection are common characteristics of both tumors. We report the specificity of surgical management, functional results and seizure outcome in cases of a tumor location in eloquent areas.Methods. - Among 150 patients (88 males, 3-55 years) operated on for refractory epilepsy due to a glioneuronal tumor (1990-2015), 30 (20%, dysembryoplastic neuroepithelial tumors = 21; gangliogliomas = 9) had a tumor located in an eloquent cortex (sensory-motor, insular or language areas). Surgery was performed after a preoperative work-up, including stereo-electroencephalography in 48 patients (26%) and functional MRI in 100 (67%). MRI-guided lesionectomy was mainly performed in extra-temporal location, whereas an additional corticectomy was performed in a temporal location. Tumor microsurgical resections were guided using neuronavigation and cortical/subcortical electrical stimulations. Multiple stereotactic thermocoagulations were performed in two insular tumors.Results. - New motor/language deficits related to eloquent areas occurred postoperatively in 6/30 patients (20%) without any major permanent disability. Minor sensorimotor (n = 2) and moderate language disturbance (n =1) persisted in three of them. Postoperative seizure-free outcome (mean follow-up > 5 years) was obtained in 81% of the entire series, but significantly decreased to 60% in eloquent areas. Incomplete tumor resection was the main cause of surgical failure. However, unfavorable seizure outcome was also observed despite complete tumor resection. Malignant transformation occurred in one ganglioglioma.Conclusion. - Epilepsy surgery for benign glioneuronal tumors in eloquent areas provides acceptable results regarding the functional risks. Complete tumor resection is crucial for long-term favorable outcome. (C) 2017 Elsevier Masson SAS. All rights reserved.

The first-line treatment of cerebral tumors or low-grade epilepsy-associated neuroepithelial tumors starts by surgical resection. The extent of resection is related to progression free survival and overall survival for patients suffering from brain tumors, and to the seizure control in patients harboring low-grade epilepsy-associated neuroepithelial tumors. Nowadays, no operative tool allow to know precisely and in real time the tissue's nature during glioma resection: healthy tissue, infiltrated tissue or tumor? Optical imaging has developed significantly at the end of the 20th century and at the beginning of the 21st century: it is possible to obtain information about the tissue's nature with a micrometric resolution and fast acquisition. Concerning surgical oncology, optical imaging seems able to guide the surgeon during tumor resection, in order to remove pathological tissue while respecting healthy tissue. This article summarizes the experience of the Sainte Anne Hospital in optical imaging with two complementary methods: the tissue endogenous fluorescence analysis with two-photon microscopy in collaboration with the IMNC laboratory and the full field optical coherence tomography in collaboration with the Langevin Institute. Endogenous fluorescence is obtained without any dye: the biological tissues possess naturally fluorescent molecules. Endogenous fluorescence analysis can be realized with two-photon microscopy: it allows to obtain 4 different optical contrasts: spectral imaging, fluorescence lifetime, second harmonic generation signal and fluorescence. This optical imaging method exhibits a fast acquisition time and a micrometric resolution. Endogenous fluorescence analysis of fixed fresh human brain samples showed that there were significant differences between tumor and healthy tissue.

In this work, we study the spectral and fluorescence lifetime of endogenous fluorescence of tumoral and healthy human tissues. Measurements were taken using endoscope and classical microscopy. The aim of this work is proving the efficiency of our endoscope in differentiating tissue nature, using a bimodal detection configuration.

Current surgical biopsy needs several days for the analysis process to be finished. Anatomopathologists provide analysis reports to the surgeon a few days after the surgical intervention, which makes it a lengthy decision making practice. In addition, the lack of precise guidance often leads to inaccuracies in the selection of tissue regions for biopsy and so necessitates repeating the operation sometimes. Our project aims at reducing this time as well as patient discomfort. In this context, we propose to develop a multimodal nonlinear endomicroscope providing several means of contrast. Among these contrast that are useful in the detection of tumor regions, we note imaging by linear and non-linear fluorescence, by second and third harmonic generation and by re flectance. In addition, this technique allows fluorescence lifetime and spectral measurements. Our endomicroscopic system is based on a new homemade customized double-clad photonic crystal fiber (DC-PCF). Finally, this double-clad micro structured optical fiber insures visible and near infrared excitation. This system was tested by measuring fluorescence lifetime and the spectral shape of a fixed tumoral brain sample in one and two photon excitations.

In order to build a multimodal nonlinear endomicroscope to image brain border during operation, our group is building an optical database on brain biopsy tissues analysis collected with excitation panning from deep UV to near infrared. This paper focuses on the results from deep UV excitation of endogenous fluorescence from glioblastoma and control human brain samples. The samples were imaged and spectrally analysed. The excitation wavelengths were tuned from 275 nm to 340 nm. Two promising indicators to discriminate tumorous tissue from the control were found. A preliminary correspondence between fluorescence images and histological H&E staining open a huge door to confirm results with a medical expertise.

Évaluation de l’efficacité et la tolérance de l’étendue de résection et de l’implantation de Gliadel® dans le traitement de première intention des glioblastomes de l’adulte.

Autofluorescence analysis allows new insights on human tissue without any dye in a non-invasive way and therefore seems well suited to study historical samples. An optical set-up recorded emitted autofluorescence in 1/spectral and 2/lifetime domains from different samples' regions of interest. The studied samples were a mummified right hand, bog body (Tollund Man) feet and a male Caucasian hand (control sample). Spectral analysis revealed that mummified hand exhibited broad autofluorescence spectra, whereas Tollund Man's feet exhibited a weak single peak with 405-nm excitation wavelength. Control sample spectra are weaker than that of the mummified hand but higher than the Tollund Man's feet. Lifetime measurements indicated the presence of classical endogenous fluorophores on the mummified right hand. The Tollund Man's feet exhibited two patterns of lifetime measurements: healthy zone exhibited lifetime values at four emission wavelengths but skin lesions at only two wavelengths. This first report of mummified samples' autofluorescence analysis suggests the potential of optical analysis for archeologic research. Copyright (c) 2017 John Wiley & Sons, Ltd.

The study of endogenous fluorescence appears as the future of medical imaging, coupled with a two photon excitation it could lead to numerous medical progresses, especially in early diagnosis. However due to the lack of miniaturized two photon technology it’s still a largely unknown field. As we project to build such a device, we also study the endogenous response of human brain biopsy under a two-photon excitation. The samples were excited with wavelengths between 700 and 980 nm and the spectral responses were measured. Two types of samples were study, thin and thick ones, the thick biopsy had a broader spectrum at each wavelength. Moreover three interesting wavelength were found, 750 nm that excite the most NADH molecules, 850 nm were we measure second harmonic generation (SHG) and a fluorescence were FAD molecules are predominant and 890 nm were SHG is the dominant response.

We present a customized small-core double-clad photonic crystal fiber for spectral and fluorescence lifetime measurements of human samples. In this Letter, the new fiber has been characterized on different fluorophores and samples of human brain tumor; a comparison to a bi-fiber homemade system and a commercial fiber probe was made.

Analysis of human tissue endogenous fluorescence is becoming a new modality of medical imaging. Its capacities represent the missing link between macroscopic radiological tools such as MRI and CT-scan and the surgeon view during surgical procedures. However, numerous aspects of this signal are not well known. Time dependence is one of these aspects. The aim of this work is to investigate the autofluorescence changes with time. Five ex vivo human samples were studied. Spectral and lifetime measurements were acquired each hour. Fluorescence intensity decreased slightly with time. This decrease existed for healthy and tumoral samples and did not affect the differences between them: higher fluorescence intensity for control samples compared to tumor samples. Lifetime values showed a slight decrease too for both type of tissue. This work is the first report of fresh human brain samples multimodal autofluorescence analysis with time.

Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high-frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high-field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Prooffor a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Althoughreview of current strategies underscores the serious shortcomings of treatment-resistant cases, initial evidence from novel approaches suggests that future success is possible.