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Статті в журналах з теми "Diffuse Low-Grade Glioma (DLGG)":
1
Darlix, Amélie, Emmanuel Mandonnet, Christian F. Freyschlag, Daniel Pinggera, Marie-Therese Forster, Martin Voss, Joachim Steinbach, et al. "Chemotherapy and diffuse low-grade gliomas: a survey within the European Low-Grade Glioma Network." Neuro-Oncology Practice 6, no. 4 (December 13, 2018): 264–73. http://dx.doi.org/10.1093/nop/npy051.
Анотація:
Abstract Background Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. Methods An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. Results The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression. Conclusions The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues.
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Mansouri, Alireza, Karanbir Brar, and Michael D. Cusimano. "Considerations for a surgical RCT for diffuse low-grade glioma: a survey." Neuro-Oncology Practice 7, no. 3 (November 12, 2019): 338–43. http://dx.doi.org/10.1093/nop/npz058.
Анотація:
Abstract Background Diffuse low-grade gliomas (DLGGs) are heterogeneous tumors that inevitably differentiate into malignant entities, leading to disability and death. Recently, a shift toward up-front maximal safe resection of DLGGs has been favored. However, this transition is not supported by randomized controlled trial (RCT) data. Here, we sought to survey the neuro-oncology community on considerations for a surgical RCT for DLGGs. Methods A 21-question survey focusing on a surgical RCT for DLGGs was developed and validated by 2 neurosurgeons. A sample case of a patient for whom management might be debatable was presented to gather additional insight. The survey was disseminated to members of the Society for Neuro-Oncology (SNO) and responses were collected from March 16 to July 10, 2018. Results A total of 131 responses were collected. Sixty-three of 117 (54%) respondents thought an RCT would not be ethical, 39 of 117 (33%) would consider participating, and 56 of 117 (48%) believed an RCT would be valuable for determining the differing roles of biopsy, surgery, and observation. This was exemplified by an evenly distributed selection of the latter management options for our sample case. Eighty-three of 120 (69.2%) respondents did not believe in equipoise for DLGG patients. Quality of life and overall survival were deemed equally important end points for a putative RCT. Conclusions Based on our survey, it is evident that management of certain DLGG patients is not well defined and an RCT may be justified. As with any surgical RCT, logistic challenges are anticipated. Robust patient-relevant end points and standardization of perioperative adjuncts are necessary if a surgical RCT is undertaken.
3
Silva, Melissa, Catalina Vivancos, and Hugues Duffau. "The Concept of «Peritumoral Zone» in Diffuse Low-Grade Gliomas: Oncological and Functional Implications for a Connectome-Guided Therapeutic Attitude." Brain Sciences 12, no. 4 (April 15, 2022): 504. http://dx.doi.org/10.3390/brainsci12040504.
Анотація:
Diffuse low-grade gliomas (DLGGs) are heterogeneous and poorly circumscribed neoplasms with isolated tumor cells that extend beyond the margins of the lesion depicted on MRI. Efforts to demarcate the glioma core from the surrounding healthy brain led us to define an intermediate region, the so-called peritumoral zone (PTZ). Although most studies about PTZ have been conducted on high-grade gliomas, the purpose here is to review the cellular, metabolic, and radiological characteristics of PTZ in the specific context of DLGG. A better delineation of PTZ, in which glioma cells and neural tissue strongly interact, may open new therapeutic avenues to optimize both functional and oncological results. First, a connectome-based “supratotal” surgical resection (i.e., with the removal of PTZ in addition to the tumor core) resulted in prolonged survival by limiting the risk of malignant transformation, while improving the quality of life, thanks to a better control of seizures. Second, the timing and order of (neo)adjuvant medical treatments can be modulated according to the pattern of peritumoral infiltration. Third, the development of new drugs specifically targeting the PTZ could be considered from an oncological (such as immunotherapy) and epileptological perspective. Further multimodal investigations of PTZ are needed to maximize long-term outcomes in DLGG patients.
4
Darlix, Amélie, Valérie Rigau, Julien Fraisse, Catherine Gozé, Michel Fabbro, and Hugues Duffau. "Postoperative follow-up for selected diffuse low-grade gliomas with WHO grade III/IV foci." Neurology 94, no. 8 (January 22, 2020): e830-e841. http://dx.doi.org/10.1212/wnl.0000000000008877.
Анотація:
ObjectiveDiffuse low-grade gliomas (DLGG) are defined by continuous growth and an almost unavoidable malignant transformation. Foci of malignant glioma can be found within DLGG samples obtained from surgical resections. As the medical management of patients is classically based on the higher tumor grade, an immediate adjuvant treatment is usually proposed. To determine whether postponing the medical treatment in selected patients is feasible, we conducted a single-center retrospective study.MethodsThis was a single-center retrospective analysis of a consecutive series of DLGG managed with this conservative strategy. Inclusion criteria were at least 1 focus of malignant tumor (grade III–IV, WHO 2016), no previous chemotherapy or radiotherapy, no less than a subtotal resection of the fluid-attenuated inversion recovery tumor volume, no intention of treating with immediate adjuvant therapy, and minimum 2 years of follow-up. The time interval to the following oncologic medical treatment was analyzed, as well as the functional and survival results.ResultsForty-four patients met the inclusion criteria (median age 36, median time interval from diagnosis 7 months). Most tumors (88%) were IDH-mutant and 1p19q intact (59%); 9 presented with grade IV foci. With a median follow-up of 6.7 years, 75% of patients received a subsequent medical treatment, after a median time of 3.4 years since surgery. At the time of analysis, 9 patients (20.0%) had died (5- and 7-year survival rates: 95% and 67.0%). Most surviving patients were still active professionally, without seizures.ConclusionsPostponing the medical treatment in DLGG with foci of malignant tumor following total or subtotal resection should be considered in selected patients.
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Zhang, Kai, Dingyang Liu, Zhuanyi Yang, Xuejun Li, Zhiquan Yang, and Xinghui He. "Resective surgery for patients with frontal lobe diffuse low-grade glioma-related epilepsy: predictors of seizure outcomes." Therapeutic Advances in Chronic Disease 13 (January 2022): 204062232211418. http://dx.doi.org/10.1177/20406223221141856.
Анотація:
Background: Diffuse low-grade gliomas (DLGGs) are prone to invade the frontal lobes, with seizures being the most common symptom. However, limited attention has been paid to surgical outcomes and their predictors in patients with frontal DLGG-related epilepsy. Objective: This study aimed to analyze predictors of postoperative seizure outcomes in patients with frontal DLGG-related epilepsy. Design: This is a single-center retrospective study. Methods: This study retrospectively collected data of 115 patients with frontal DLGG-related epilepsy who underwent resective surgery between January 2014 and January 2021. Patients were categorized into favorable and unfavorable seizure outcome groups based on the International League Against Epilepsy (ILAE) classification. Univariate and multivariate analyses were used to identify potential predictors of seizure outcomes. Results: The mean follow-up was 4.11 ± 2.06 years, and 77.4% (89 of 115) of patients were seizure-free. Permanent neurological deficits were observed in 7.0% (8 of 115) of patients. Univariate and multivariate analyses revealed that total tumor removal [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.12–0.82; p = 0.018] and older age at seizure onset (OR, 0.96; 95% CI, 0.93–0.99; p = 0.042) were independent predictors of favorable seizure outcomes. Conclusion: Surgical resection is an effective treatment for frontal DLGG-related epilepsy. Favorable seizure outcomes are more likely to be achieved in patients with complete tumor removal and those with older age at seizure onset.
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Alvarez de Eulate-Beramendi, Sayoa, Valérie Rigau, Luc Taillandier, and Hugues Duffau. "Delayed leptomeningeal and subependymal seeding after multiple surgeries for supratentorial diffuse low-grade gliomas in adults." Journal of Neurosurgery 120, no. 4 (April 2014): 833–39. http://dx.doi.org/10.3171/2013.10.jns131512.
Анотація:
Object Diffuse WHO Grade II glioma (diffuse low-grade glioma [DLGG]) is an infiltrative brain tumor that usually migrates along the white matter fibers. The delayed CSF dissemination of supratentorial DLGGs is an exceptional complication and is rarely described in adults. Here, the authors report outcomes in a surgical series of 9 patients with DLGGs with subsequent leptomeningeal and/or subependymal seeding (LMSS) following multiple incomplete resections. Methods The authors performed a retrospective review of patients who underwent surgery for histopathologically confirmed WHO Grade II gliomas between 1998 and 2012 and experienced a secondary CSF spread. Information regarding clinical features, surgical procedures, histopathological results, adjuvant treatment, and clinical outcomes was collected and analyzed. Results Nine consecutive patients were included in this study. There were 6 men and 3 women whose mean age was 35.5 years (range 22–59 years) at the time of initial symptom onset. All patients underwent surgery with the aid of intraoperative mapping, with incomplete tumor removal because of invasion of eloquent structures. The neuropathological examination diagnosed a DLGG in all cases (7 oligodendrogliomas, 1 astrocytoma, and 1 oligoastrocytoma). Five patients had a 1p19q codeletion. Because of tumor regrowth, the 9 patients underwent reoperation (2 surgeries in 6 cases and 3 surgeries in 3 cases), again with incomplete resection. There were no surgical complications. Adjuvant therapy (radiotherapy and chemotherapy) was administered in all patients because of progression to a higher grade of malignancy that was histopathologically confirmed in all tumors. The patients suddenly worsened, and the diagnosis of LMSS was made with a mean delay of 77 months (range 27–140 months) after the initial symptom onset. Six patients benefited from salvage chemotherapy while palliative care was chosen in 3 cases. The median survival in the 6 patients who underwent LMSS treatment was significantly longer than that in the 3 patients who did not receive salvage chemotherapy (p = 0.03). Indeed, all patients died, with a mean delay between the diagnosis of LMSS and death of 11 months (range 2–38 months) and with a mean delay between the initial symptom onset and death of 88 months (range 34–144 months). Conclusions Cerebrospinal fluid dissemination of DLGG is a rare but possible event. It can occur throughout the progression of WHO Grade II oligodendrogliomas, oligoastrocytomas, and astrocytomas, regardless of 1p19q status. This complication seems to appear in patients who have undergone multiple incomplete resections. Salvage therapy can be considered in patients with good neurological status. However, LMSS is associated with a decreased overall survival. Therefore, this rare entity deserves further multicenter studies to better understand its pathophysiology and to adapt therapeutic strategies.
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Levine, Adrian, Cyril Li, Joseline Haizel-Cobbina, Liana Nobre, Julie Bennett, Michael Dewan, Uri Tabori, and Cynthia Hawkins. "LGG-12. CLINICAL AND MOLECULAR FEATURES OF DISSEMINATED PEDIATRIC LOW-GRADE GLIOMA." Neuro-Oncology 25, Supplement_1 (June 1, 2023): i58. http://dx.doi.org/10.1093/neuonc/noad073.222.
Анотація:
Abstract Although most pediatric LGG (PLGG) have excellent long-term survival, there is a subset of cases that disseminate throughout the neuraxis (DLGG) that have very poor outcomes. The reason for this aggressive behavior is unknown but we hypothesize that distinct and specific biological mechanisms underlie the metastatic ability. The methylation-based class of diffuse leptomeningeal glioneuronal tumor (DLGNT) is characterized by MAPK pathway activating fusions with chromosome 1p loss, 19q loss, and/or 1q gain. However, it is unknown what proportion of DLGG match the DLGNT group, and which other methylations classes are at risk of metastasis. To improve our understanding of this rare patient population, we created an international DLGG consortium. Data from the first 68 cases shows a broad age distribution and no sex predilection. As expected, DLGG has much worse prognosis than the overall PLGG population. Virtually all DLGG progress at 5 years, compared to a quarter of other PLGG, and DLGG are 5-times more likely to die at 10 years. We observe three patterns of dissemination – 35% present with a localized mass and have secondary dissemination, 50% with disseminated tumor and a clear dominant mass, and 15% with disseminated disease without a dominant mass. In 47 patients with molecular testing, BRAF fusions accounted for 64% of driver alterations. Additional alterations were identified less frequently, including BRAF V600E (9%), FGFR1 alterations (9%), and KRAS mutations (4%). In 25 patients with methylation profiling, 10 (40%) successfully classified with a calibrated score above 0.8, illustrating that many cases do not fit a defined methylation group. The most common methylation classification was pilocytic astrocytoma (5 patients), and surprisingly only two patients classified as DLGNT. In sum this study illustrates the variable clinical behaviour associated with metastasis in PLGG and expands the range of molecular driver alterations, including ones previously unreported in DLGNT.
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Ali Khan, Ahsan, Mohammad Hamza Bajwa, Noman Khan, Muhammad Usman Khalid, Fatima Mubarak, and Syed Ather Enam. "NIMG-76. DISCRETE LOWER-GRADE GLIOMA (DLGG) VERSUS INFILTRATIVE LOWER-GRADE GLIOMA (ILGG): CORRELATION OF RADIOLOGICAL CHARACTERISTICS WITH CLINICAL OUTCOMES." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi146—vi147. http://dx.doi.org/10.1093/neuonc/noab196.573.
Анотація:
Abstract INTRODUCTION Lower grade gliomas encompass grade 2 and 3 tumors. However, this term is more generalized and does not include the spectrum of radiological and tumor morphological patterns seen. Here we have established two distinct patterns of radiographic appearance seen within lower grade gliomas: ILGG and DLGG. Imaging plays a vital role in diagnosis, surveillance, characterization, and monitoring of intracranial tumors. Of particular importance is the differentiation of tumor features to reliably predict malignancy, tumor grade, possible molecular or genetic features, disease progression and recurrence, potential for malignant transformation, and postoperative outcomes. Our study will look at these radiographic characteristics of diffuse and infiltrating lower grade gliomas and discuss their predictive value. Understanding the distinct nature of these varieties of LGG will help us in surgical decision-making, prognostication, biopsy target and precision medicine. METHODS Pre-operative and post-operative MRI images of Grade 2 and 3 tumors were identified and analyzed in order to extract radiographic data, and correlated with patient demographics, clinical outcomes, extent of surgical resection, and molecular genetic analysis. RESULTS Out of 35 patients evaluated, 22 (62.9%) were labeled ILGGs and 13 (37.1%) were deemed DLGGs according to the pre-defined criteria. T2 habitat was higher in ILGG (mean = 2162) than DLGG (mean = 1482) as well as size, in cm (6.02 vs. 4.92). ADC habitat, lesion ADC, and percentage of the lesion that showed contrast-enhancement were similar. T2-FLAIR mismatch was significantly higher in ILGG (p = 0.02). Post-operative KPS scores were significantly higher in the DLGG group (p = 0.03). CONCLUSION T2-FLAIR mismatch can be a significant classifier for lower-grade gliomas. Our study shows there are differences in tumor morphology of diffuse and infiltrative lower-grade gliomas which can be correlated to outcomes after surgery. *Indicates corresponding author.
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Hamidi, Nima, Ajay Fernandez, Kyle Tuohy, and Alireza Mansouri. "QOLP-09. HEALTH ECONOMIC EVALUATION OF LOW-GRADE GLIOMA MANAGEMENT: A SYSTEMATIC REVIEW." Neuro-Oncology 22, Supplement_2 (November 2020): ii176. http://dx.doi.org/10.1093/neuonc/noaa215.734.
Анотація:
Abstract BACKGROUND Diffuse low-grade gliomas (DLGGs, WHO Grade II gliomas) comprise 13-16% of all primary brain tumors. Although there has been a paradigmatic shift toward upfront maximal safe resection (MSR) for these heterogeneous tumors, it is important to consider the health economic perspective of this approach, compared with the traditional watch-and-wait approach, as well. OBJECTIVE To conduct a systematic review of the health economic literature on the range of DLGG management options. METHODS Following the PRISMA guidelines, Medline, EMBASE, The Central Registration Depository (CRD), EconPapers, and EconLit were searched for ‘cost-effectiveness’, ‘health economics’ and ‘Low-grade glioma’. Grade I tumors were excluded. Pre-specified variables were extracted. All currencies were converted to USD. RESULTS Among 258 abstracts, 28 were selected for full-text screening, and 3 were selected for this review. A European study evaluated the role of intraoperative electrical stimulation (IES). Although IES was associated with higher direct costs upfront ($38,662.70 vs $32,116.10), this was offset by less long-term indirect costs ($12,222.30 vs $31,927.10; p=0.023), greater QALY (4.8 vs 2.9; p=0.001), and an incremental cost-effectiveness ratio (ICER) of $1,842.50. Another study evaluated the cost-effectiveness of adjuvant PCV+RT vs RT alone, finding greater QALY for the former (9.94 vs 5.17) and an ICER of $10,186 per QALY gained. A third study evaluated the cost-effectiveness of adding 18F-fluoroethyl-L-tyrosine (FET) PET to MRI, compared to preoperative MRI alone. This resulted in an ICER of $7,193.58 for the baseline scenario (lowest reimbursement) and $10,236.12 for the morbidity-adjusted reimbursement rate scenario (highest reimbursement). There were no studies evaluating the health economics of maximal upfront surgical resection to the watch-and-wait approach. CONCLUSION We found a limited number of studies reporting on the health economics of DLGGs. Given the paradigmatic transition toward more aggressive upfront surgical resection, DLGG-specific health economic analyses are underway.
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Zetterling, Maria, Kenney R. Roodakker, Shala Ghaderi Berntsson, Per-Henrik Edqvist, Francesco Latini, Anne-Marie Landtblom, Fredrik Pontén, Irina Alafuzoff, Elna-Marie Larsson, and Anja Smits. "Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data." Journal of Neurosurgery 125, no. 5 (November 2016): 1155–66. http://dx.doi.org/10.3171/2015.10.jns15583.
Анотація:
OBJECTIVE Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed. METHODS Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices. RESULTS Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H–positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences. CONCLUSIONS The authors present a new method for the coregistration of histological and radiological characteristics of en bloc–removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.
Дисертації з теми "Diffuse Low-Grade Glioma (DLGG)":
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Brzenczek, Cyril. "Modélisation multi-facteurs pour l’aide à la décision dans le traitement par chimiothérapie des tumeurs cérébrales de type gliome diffus de bas grade." Electronic Thesis or Diss., Université de Lorraine, 2021. http://www.theses.fr/2021LORR0095.
Анотація:
Le Gliome Diffus de Bas Grade (GDBG) est défini par l’OMS comme une tumeur primitive du système nerveux central et représente 15% de toutes les tumeurs gliales confondues. Un GDBG croît lentement, et finit inévitablement par se transformer en un gliome de grade III, bien plus agressif, qui mène finalement au décès du patient. Trois types de traitements sont disponibles : La chirurgie, la chimiothérapie et la radiothérapie. Aujourd’hui, les médianes de survie rapportées dans les études sont de 10 à 15 ans. Malheureusement, le pronostic du GDBG est très variable, l’écart-type de la survie totale étant élevé, et certains patients ne survivant que quelques années. Dans le cadre de la prise en charge du GDBG au CHRU de Nancy, la chimiothérapie est un des traitements les plus utilisés et on observe des réponses très variables tant en intensités, qu’en durées ainsi qu’en terme de profils de réponses. C’est dans ce contexte que se situe le travail de thèse. Il concerne l’étude de la réponse à la chimiothérapie et consiste à développer des outils d’aide à la décision pour le neuro-oncologue dans le suivi des patients. La première partie de mon travail de thèse se concentre donc sur le choix de la méthode de volumétrie. On peut ensuite caractériser la courbe de réponse volumique selon l’intensité de réponse. La seconde partie de ce travail concerne la modélisation de la réponse à l’aide de techniques d’apprentissage statistique. De nombreuses variables explicatives (épidémiologiques, génétiques sont à prendre en compte dans cette étude, dont une nouvelle variable nommée ESVR, qui est une mesure permettant de quantifier le phénotype infiltrant des GDBG. Les méthodes d’analyse factorielle et de machine learning permettent dans un premier temps de définir les variables qui portent le plus d’information. Les analyses exploratoires des données révèlent une redondance de l’information parmi certains facteurs génétiques et épidémiologiques. Les modèles montrent une plus grande influence des variables quantitatives sur la réponse à la chimiothérapie, comparé aux variables qualitatives. Une discussion sera menée sur l’importance des variables utilisées dans la prédiction de la réponse à la chimiothérapie. La finalité de la thèse est de produire un ensemble de règles qui permettront aux cliniciens d’anticiper, avant l’administration du traitement, son effet sur le volume tumoral ce qui permettra un choix de stratégie thérapeutique plus éclairé qu’aujourd’huiDiffuse Low-Grade Glioma (DLGG) is defined by the WHO as a primary tumour of the central nervous system and represents 15% of all glial tumours combined. A DLGG grows slowly, and inevitably evolve into a much more aggressive (grade III) glioma, which eventually leads to the death of the patient. Three types of treatment are available: surgery, chemotherapy and radiotherapy. Today, the median survival rates reported in studies varies from 10 to 15 years. Unfortunately, the prognosis for DLGG is highly variable, with a high standard deviation of total survival, and some patients are surviving only a few years. Within the framework of DLGG management at Nancy University Hospital, chemotherapy is one of the most widely used treatments and there are very variable responses in terms of intensity, duration and response profiles. The thesis work is located in this context. It concerns the study of the response to chemotherapy and consists in developing decision-making tools for the neuro-oncologist in the follow-up of patients. The first part of this thesis work therefore focuses on the choice of the volumetric method. The volume response curve can then be characterised in terms of response intensity. The second part of this work concerns response modelling using statistical learning techniques. Many explanatory variables (epidemiological, genetic) are under study. A new variable called ESVR, which is an original measure allowing us to quantify the infiltrating DLGG phenotype, will also be used. The factorial analysis and machine learning methods initially make possible to define the variables that provide the most information. Exploratory analyses of the data reveal a redundancy of information among certain genetic and epidemiological factors. The models show a greater influence of quantitative variables on the response to chemotherapy compared to qualitative variables. A discussion is finally produced on the importance of the variables used in the prediction of the response to chemotherapy. The aim of this thesis is to produce a set of rules which will enable clinicians to anticipate, before administering the treatment, its effect on tumour volume, which will allow a more advised choice of therapeutic strategy than possible nowadays
2
Konnully, Augustus Meera Bessy. "Characterization of cellular heterogeneity in Diffuse Low Grade Glioma." Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTT038.
Анотація:
Les gliomes diffus de bas grade (DLGG) sont des tumeurs gliales de grade II qui affectent principalement les jeunes adultes. Elles sont caractérisées par une croissance lente et une activité mitotique réduite. Cependant, ces tumeurs diffusent et envahissent le cerveau sain via les vaisseaux sanguins et les fibres nerveuses. Après plusieurs années de croissance lente, ces tumeurs peuvent évoluer vers des glioblastomes, des tumeurs cérébrales très agressives dont la survie médiane moyenne est alors de 12 à 15 mois après le diagnostic. La caractérisation cellulaire des DLGG est encore limitée ce qui nuit à la recherche d’un traitement à un stade précoce. Dans ma thèse de doctorat, je me suis focalisée sur la caractérisation de 'hétérogénéité cellulaire des DLGG mutés pour IDH1. En effectuant une analyse d'immunofluorescence sur des astrocytomes et oligodendrogliomes de grade II, j'ai identifié deux sous-populations cellulaires largement non chevauchantes et exprimant respectivement les facteurs de transcription SOX9 et OLIG1. Ces cellules s’apparentent à des cellules de type astrocytaire et oligodendrocytaire et expriment des marqueurs moléculaires distincts. Les cellules SOX9 expriment APOE, KCNN3, CRYAB et ID4, tandis que les cellules OLIG1 expriment préfentiellement PDGFRA, SOX8, MASH1 et SOX4. Par ailleurs, j’ai montré que les cellules SOX9 présentent une activation particulière des voies de signalisation, notamment Notch, BMP et leurs cibles en aval. Pour étudier le rôle de la voie de signalisation Notch dans la formation de ces 2 sous-populations tumorales, j'ai purifié par tri magnétique les cellules tumorales à partir d'échantillons de gliomes fraîchement réséqués et j'ai surexprimé le domaine intracellulaire Notch (NICD), une forme active de Notch. J’ai ainsi montré que cette activation augmentait l’expression des marqueurs cellulaires associés aux cellules SOX9+ et une baisse de ceux associés aux cellules OLIG1+. J'ai ensuite étendu ces analyses à une lignée cellulaire anaplasique dérivée d'un patient et mutée pour IDH1. Ces résultats indiquent un rôle clé de la signalisation Notch dans la régulation de la plasticité des cellules tumorales. Des expériences similaires pour étudier l'activation de la signalisation BMP (bone morphogenetic protein) n'ont pas montré d'effet notable sur la plasticité. Néanmoins, le traitement des cellules par des membres de la famille BMP a fortement augmenté l’expression de CRYAB, un marqueur associé à SOX9, et a diminué l’expression de OLIG1 et OLIG2. En conclusion, j'ai identifié deux sous-populations tumorales non chevauchantes dans des gliomes diffus de bas grade et j'ai démontré le rôle déterminant de la voie de signalisation Notch dans leur formation. Ces résultats permettront de mieux comprendre l'hétérogénéité tumorale dans les DLGG et de concevoir de nouvelles stratégies thérapeutiques contre ces tumeursDiffuse Low-Grade Gliomas (DLGG) are WHO grade II glial tumors affecting younger adults. They are characterized as silent, slow growing tumors with fewer mitotic activities. However, they diffuse and invade the healthy brain via blood vessels and nerve fibers. These, over a period of years develop to malignant Glioblastoma, aggressive brain tumors where patients have an average medial survival of 12-15 months after diagnosis. Ill-defined phenotypic and cellular diversity of DLGG poses serious limitation to treatment and prevention at the early stage.In my PhD thesis, I aimed to address this limitation by characterizing the cellular heterogeneity in IDH1-mutated DLGG. By performing immunofluorescence analysis on grade II astrocytoma and oligodendroglioma, I have identified two largely non-overlapping cellular subpopulations expressing SOX9 and OLIG1 transcription factors, which represent astrocyte-like and oligodendrocyte-like cells, respectively. Upon further investigation, I have shown that these subpopulations express distinct molecular markers. Sox9 cells are associated with APOE, KCNN3, CRYAB and ID4, while Olig1 cells showed strong correlation with the expression of PDGFRA, SOX8, MASH1, and SOX4. In addition, the sox9 cells show a particular activation of signaling pathways including Notch, BMP and their downstream targets.To ascertain the role of Notch signaling in regulating the formation of these tumoral subpopulations, I used magnetic sorting of tumor cells from freshly resected glioma samples and overexpressed Notch Intracellular Domain (NICD), an active form of Notch. Increased Notch activation resulted in an upregulation of Sox9- and downregulation of Olig1-associated cell markers. I have then extended these analyses on one anaplastic IDH1 mutated patient derived cell line which reproduced similar gene expression profile confirming the robustness of the role of Notch signaling in regulating the plasticity of the cells. Parallel experiments performed by activation of Bone Morphogenetic Protein (BMP) signaling on IDH1 mutated cell line did not show a prominent effect on the plasticity. Nevertheless, BMP signal activation highly upregulated CRYAB, a SOX9 related marker and downregulated OLIG1 and OLIG2.In conclusion, I have identified two non-overlapping tumor subpopulations in diffuse low-grade gliomas and demonstrated the deterministic role of Notch signaling pathway in their formation. I believe that these findings would aid in better understanding tumoral heterogeneity in DLGG and be extended in designing new therapeutic strategies against these tumors
3
Ben, Abdallah Mériem. "Un modèle de l'évolution des gliomes diffus de bas grade sous chimiothérapie." Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0215/document.
Анотація:
Les gliomes diffus de bas grade sont des tumeurs cérébrales des jeunes adultes. Dans cette thèse, nous nous intéressons à la segmentation et à la modélisation de ces tumeurs. Dans la première partie du manuscrit, nous étudions la segmentation des gliomes diffus de bas grade à base de différentes méthodes manuelles et semi-automatiques. La délimitation de ces tumeurs peut être problématique en raison de leur caractère très infiltrant et inhomogène. En pratique clinique, le suivi des gliomes diffus de bas grade repose sur l'estimation du volume tumoral, soit par une segmentation suivie d'une reconstruction logicielle, soit par la méthode des trois diamètres. Pour la segmentation, elle est manuelle et est exécutée par des praticiens sur des IRM en pondération FLAIR ou T2. La méthode des trois diamètres est rapide mais s'avère difficile à implémenter dans le cas de gliomes diffus de bas grade très infiltrants ou en post-traitement. La solution par segmentation manuelle et reconstruction logicielle du volume est chronophage mais demeure plus précise en comparaison de la méthode des trois diamètres. Nous étudions ici la reproductibilité de la segmentation manuelle avec le logiciel OsiriX en réalisant un test subjectif dans le Living Lab PROMETEE de TELECOM Nancy. Les résultats de cette étude montrent que ni la spécialité du praticien ni le nombre d’années d’expérience ne semblent impacter significativement la qualité de la segmentation. Nous comparons par ailleurs les résultats obtenus à ceux d'un deuxième test où nous appliquons la méthode des trois diamètres. Enfin, nous explorons deux algorithmes de segmentation semi-automatique basés, respectivement, sur les contours actifs et sur la méthode des level set. Même si la segmentation automatique semble être une voie prometteuse, nous recommandons aujourd’hui l’utilisation de la segmentation manuelle du fait notamment du caractère diffus des gliomes de bas grade qui rend le contour complexe à délimiter. La seconde partie du manuscrit est consacrée à la modélisation des gliomes diffus de bas grade eux-mêmes ou, plus exactement, à la modélisation de l'évolution du diamètre tumoral en phase de chimiothérapie. La prise en charge thérapeutique des patients atteints de ces tumeurs inclut en effet souvent une chimiothérapie. Pour ce travail, nous nous intéressons à la chimiothérapie par Témozolomide en première ligne de traitement. Une fois le traitement entamé, les praticiens aimeraient déterminer l'instant optimal d'arrêt de traitement. Nous proposons une modélisation statistique du diamètre tumoral sous chimiothérapie. Cette modélisation s'appuie sur des modèles de régression linéaire et exponentielle. Elle permet de prédire le diamètre tumoral à partir d'un jeu de données d'apprentissage et d'alerter le clinicien sur l'état d'évolution du diamètre sous traitement. Nous espérons que ces modèles pourront un jour être utilisés comme un outil dans la planification de la chimiothérapie en milieu cliniqueDiffuse low-grade gliomas are brain tumors of young adults. In this thesis, we focus on the segmentation and on the modeling of these tumors. In the first part of the manuscript, we study the segmentation of diffuse low-grade gliomas based on different manual and semi-automatic methods. The delineation of these tumors can be problematic because of their very infiltrating and inhomogeneous nature. In clinical practice, the monitoring of diffuse low-grade gliomas is based on the estimation of tumor volume, obtained either through a segmentation followed by a software reconstruction or through the three diameters method. As for the segmentation, it is manual and it is performed by practitioners on FLAIR-weighted or T2-weighted MRI.The three diameters approach is fast but it is difficult to implement in the case of highly infiltrating diffuse low grade gliomas or after a treatment. The manual segmentation and software-based volume reconstruction solution is time-consuming but it remains more accurate in comparison with the three diameters method. We investigate in this work the reproducibility of the manual segmentation with the OsiriX software by performing a subjective test in the Living Lab PROMETEE in TELECOM Nancy. The results of this study show that neither the practitioners' specialty nor their number of years of experience seem to have a significant impact on the quality of the segmentation. We also compare the results to those of a second test where we apply the three diameters method. Finally, we explore two semi-automatic segmentation algorithms which are, respectively, based on active contours and on the level set method. Even if automatic segmentation seems to be a promising avenue, we recommend for now the use of manual segmentation because of the diffuse nature of low-grade gliomas, which makes the tumor's contours complex to delineate. The second part of the manuscript is dedicated to the modeling of diffuse low-grade gliomas themselves or, to be more precise, to the modeling of the evolution of the tumor's diameter during chemotherapy. The therapeutic management of patients with these tumors often includes indeed chemotherapy. For this work, we focus on Temozolomide chemotherapy in first-line treatment. After the beginning of the treatment, the practitioners would like to determine the optimum time of discontinuation. We propose a statistical modeling of tumor diameter under chemotherapy. This modeling is based on linear and exponential regression models. It can predict the tumor diameter from a set of training dataset and can alert the clinician on the state of change in diameter under treatment. We hope that these models will, eventually, be used as a tool in the planning of chemotherapy in a clinical environment
4
Ben, Abdallah Mériem. "Un modèle de l'évolution des gliomes diffus de bas grade sous chimiothérapie." Electronic Thesis or Diss., Université de Lorraine, 2016. http://www.theses.fr/2016LORR0215.
Анотація:
Les gliomes diffus de bas grade sont des tumeurs cérébrales des jeunes adultes. Dans cette thèse, nous nous intéressons à la segmentation et à la modélisation de ces tumeurs. Dans la première partie du manuscrit, nous étudions la segmentation des gliomes diffus de bas grade à base de différentes méthodes manuelles et semi-automatiques. La délimitation de ces tumeurs peut être problématique en raison de leur caractère très infiltrant et inhomogène. En pratique clinique, le suivi des gliomes diffus de bas grade repose sur l'estimation du volume tumoral, soit par une segmentation suivie d'une reconstruction logicielle, soit par la méthode des trois diamètres. Pour la segmentation, elle est manuelle et est exécutée par des praticiens sur des IRM en pondération FLAIR ou T2. La méthode des trois diamètres est rapide mais s'avère difficile à implémenter dans le cas de gliomes diffus de bas grade très infiltrants ou en post-traitement. La solution par segmentation manuelle et reconstruction logicielle du volume est chronophage mais demeure plus précise en comparaison de la méthode des trois diamètres. Nous étudions ici la reproductibilité de la segmentation manuelle avec le logiciel OsiriX en réalisant un test subjectif dans le Living Lab PROMETEE de TELECOM Nancy. Les résultats de cette étude montrent que ni la spécialité du praticien ni le nombre d’années d’expérience ne semblent impacter significativement la qualité de la segmentation. Nous comparons par ailleurs les résultats obtenus à ceux d'un deuxième test où nous appliquons la méthode des trois diamètres. Enfin, nous explorons deux algorithmes de segmentation semi-automatique basés, respectivement, sur les contours actifs et sur la méthode des level set. Même si la segmentation automatique semble être une voie prometteuse, nous recommandons aujourd’hui l’utilisation de la segmentation manuelle du fait notamment du caractère diffus des gliomes de bas grade qui rend le contour complexe à délimiter. La seconde partie du manuscrit est consacrée à la modélisation des gliomes diffus de bas grade eux-mêmes ou, plus exactement, à la modélisation de l'évolution du diamètre tumoral en phase de chimiothérapie. La prise en charge thérapeutique des patients atteints de ces tumeurs inclut en effet souvent une chimiothérapie. Pour ce travail, nous nous intéressons à la chimiothérapie par Témozolomide en première ligne de traitement. Une fois le traitement entamé, les praticiens aimeraient déterminer l'instant optimal d'arrêt de traitement. Nous proposons une modélisation statistique du diamètre tumoral sous chimiothérapie. Cette modélisation s'appuie sur des modèles de régression linéaire et exponentielle. Elle permet de prédire le diamètre tumoral à partir d'un jeu de données d'apprentissage et d'alerter le clinicien sur l'état d'évolution du diamètre sous traitement. Nous espérons que ces modèles pourront un jour être utilisés comme un outil dans la planification de la chimiothérapie en milieu cliniqueDiffuse low-grade gliomas are brain tumors of young adults. In this thesis, we focus on the segmentation and on the modeling of these tumors. In the first part of the manuscript, we study the segmentation of diffuse low-grade gliomas based on different manual and semi-automatic methods. The delineation of these tumors can be problematic because of their very infiltrating and inhomogeneous nature. In clinical practice, the monitoring of diffuse low-grade gliomas is based on the estimation of tumor volume, obtained either through a segmentation followed by a software reconstruction or through the three diameters method. As for the segmentation, it is manual and it is performed by practitioners on FLAIR-weighted or T2-weighted MRI.The three diameters approach is fast but it is difficult to implement in the case of highly infiltrating diffuse low grade gliomas or after a treatment. The manual segmentation and software-based volume reconstruction solution is time-consuming but it remains more accurate in comparison with the three diameters method. We investigate in this work the reproducibility of the manual segmentation with the OsiriX software by performing a subjective test in the Living Lab PROMETEE in TELECOM Nancy. The results of this study show that neither the practitioners' specialty nor their number of years of experience seem to have a significant impact on the quality of the segmentation. We also compare the results to those of a second test where we apply the three diameters method. Finally, we explore two semi-automatic segmentation algorithms which are, respectively, based on active contours and on the level set method. Even if automatic segmentation seems to be a promising avenue, we recommend for now the use of manual segmentation because of the diffuse nature of low-grade gliomas, which makes the tumor's contours complex to delineate. The second part of the manuscript is dedicated to the modeling of diffuse low-grade gliomas themselves or, to be more precise, to the modeling of the evolution of the tumor's diameter during chemotherapy. The therapeutic management of patients with these tumors often includes indeed chemotherapy. For this work, we focus on Temozolomide chemotherapy in first-line treatment. After the beginning of the treatment, the practitioners would like to determine the optimum time of discontinuation. We propose a statistical modeling of tumor diameter under chemotherapy. This modeling is based on linear and exponential regression models. It can predict the tumor diameter from a set of training dataset and can alert the clinician on the state of change in diameter under treatment. We hope that these models will, eventually, be used as a tool in the planning of chemotherapy in a clinical environment
5
Herbet, Guillaume. "Vers un modèle à double voie dynamique et hodotopique de l'organisation anatomo-fonctionnelle de la mentalisation : étude par cartographie cérébrale multimodale chez les patients porteurs d'un gliome diffus de bas-grade." Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON1T004/document.
Анотація:
Comprendre comment le cerveau humain engendre les formes les plus élaborées de comportements est profondément lié à nos connaissances générales sur son organisation anatomique et fonctionnelle. Jusqu'à récemment encore, on pensait que les fonctions cognitives n'étaient rien d'autre que le sous-produit de l'activité neurale de régions corticales discrètes et hyper-fonctionnalisées. Les découvertes majeures obtenues ces dix dernières années dans le champ de la neuro-imagerie, et plus particulièrement de la connectomique, invitent cependant à complexifier nos représentations sur les liens qu'entretiennent structures et fonctions cérébrales. Le cerveau semble en effet être organisé en systèmes neurocognitifs complexes, hautement distribués et plastiques. C'est dans cet esprit qu'a été réalisé ce travail de thèse dont l'ambition première a été de repenser les modèles actuels de la cognition sociale, et en particulier ceux ayant trait à la fonction de mentalisation, à travers l'étude comportementale des patients porteurs d'un gliome diffus de bas-grade. Cette tumeur neurologique rare constitue un excellent modèle physiopathologique en vue du démasquage des structures maîtresses des systèmes cognitifs complexes, en ce qu'elle induit des phénomènes majeurs de réorganisation fonctionnelle, et s'infiltre préférentiellement le long de la connectivité axonale associative. Des corrélations anatomo-cliniques ont été réalisées suivant une approche topologique classique (analyse de groupe en régions d'intérêt, cartographie voxel-based lesion-symptom, stimulation électrique corticale intra-opératoire) mais également hodologique (degré de déconnection des faisceaux d'association, stimulation électrique de la connectivité axonale). Les résultats principaux de nos différents travaux nous permettent de jeter les premières bases d'un modèle à double voie dynamique (plastique) et hodotopique (contraint par la réalité anatomique) de l'organisation anatomo-fonctionnelle des processus de mentalisation. Spécifiquement, une voie dorsale, interconnectant le aires corticales fronto-pariétales « miroirs » via le système périsylvien de substance blanche associative (faisceau arqué et faisceau longitudinal supérieur latéral), sous-tendrait les processus perceptifs de « bas-niveau » nécessaires à l'identification préréflexive des états mentaux ; une voie cingulo-médiane, interconnectant les régions préfrontales médiales et rostro-cingulaires aux régions pariétales postérieures médiales via le faisceau cingulaire, sous-tendrait les processus de «haut-niveau » nécessaires aux inférences mentalistiques conscientes. Ces découvertes constituent une avancée substantielle en neurosciences sociales, ont des implications importantes pour la prise en charge clinique des patients, et peuvent permettre de mieux comprendre certaines psychopathologies caractérisées à la fois par un trouble de la mentalisation et des anomalies structurales de la connectivité associative (troubles du spectre autistique)Understanding how the brain produces sophisticated behaviours strongly depends of our knowledge on its anatomical and functional organization. Until recently, it was believed that high-level cognition was merely the by-product of the neural activity of discrete and highly specialized cortical areas. Major findings obtained in the past decade from neuroimaging, particularly from the field of connectomics, prompt now researchers to revise drastically their conceptions about the links between brain structures and functions. The brain seems indeed organized in complex, highly distributed and plastic neurocognitive networks. This is in this state of mind that our work has been carried out. Its foremost ambition was to rethink actuals models of social cognition, especially mentalizing, through the behavioural study of patients harbouring a diffuse low-grade glioma. Because this rare neurological tumour induces major functional reorganization phenomena and migrates preferentially along axonal associative connectivity, it constitutes an excellent pathophysiological model for unmasking the core structures subserving complex cognitive systems. Anatomo-clinical correlations were conducted according to both a classical topological approach (region of interest analyses, voxel-based lesion-symptom mapping, intraoperative cortical electrostimulation) and a hodological approach (degree of disconnection of associative white matter fasciculi, intraoperative axonal connectivity mapping). The main results of our different studies enable us to lay the foundation of a dynamic (plastic) and hodotopical (connectivity) dual-stream model of mentalizing. Specifically, a dorsal stream, interconnecting mirror frontoparietal areas via the perisylvian network (arcuate fasciculus and lateral superior longitudinal fasciculus), may subserve low-level perceptual processes required in rapid and pre-reflective identification of mental states; a cingulo-medial stream, interconnecting medial prefrontal and rostro-cingulated areas with medial posterior parietal areas via the cingulum, may subserve higher-level processes required in reflective mentalistic inferences. These original findings represents a great step in social neuroscience, have major implications in clinical practice, and opens new opportunities in understanding certain pathological conditions characterized by both mentalizing deficits and aberrant structural connectivity (e.g. autism spectrum disorders)
6
Lemaitre, Anne-Laure. "Métacognition et personnalité chez des patients porteurs d'un gliome diffus de bas grade : un eclairage nouveau sur le potentiel plastique du cerveau humain." Thesis, Lille 3, 2019. http://www.theses.fr/2019LIL3H059.
Анотація:
Les découvertes récentes en neuropsychologie ont permis de passer d’une conception localisationniste à une conception en réseaux dynamiques du fonctionnement cérébral. Cette révolution conceptuelle, d’un cerveau immuable à remodelable, a été étayée par l’étude des patients porteurs d’un gliome de bas grade, une tumeur primaire associée à des phénomènes majeurs de plasticité cérébrale. Toutefois, on ne sait pas actuellement si cette neuroplasticité peut s’étendre aux fonctions de haut-niveau, celles qui participent à la conscience qu’ont les individus d’eux-mêmes. L’objectif de ce travail de thèse était d’évaluer dans quelle mesure les résections chirurgicales de gliomes affectent les processus métacognitifs et les traits de personnalité, en utilisant des méthodes de corrélations anatomo-fonctionnelles qui s’appuient sur la localisation lésionnelle et les déconnexions cérébrales. Dans un premier temps, nous avons montré que des résections frontales, unilatérales et bilatérales, n’induisaient pas de trouble métaperceptif, alors que le cortex préfrontal est supposé être central dans la métacognition. De même, nos résultats suggèrent que des résections chirurgicales massives n’affectent que très peu les traits de personnalité. Néanmoins, quelques traits comme la schizotypie positive et des troubles du comportement, comme l’anosognosie, étaient associés à l’atteinte de certains faisceaux de substance blancheRecent findings in the field of neuropsychology have allowed to move from a localized to a dynamic network approach of brain functions. This paradigmatic shift, from a static to a reshaping brain, has been supported by the investigation of patients with low-grade glioma, a neurological tumor known to trigger processes of compensation and rescue of brain functions. However, it is currently unestablished whether this neuroplastic compensation may extend to higher-order cognitive functions, specifically those involved in self-consciousness. By using both anatomo-functional correlational methods based on lesions localization and structural disconnection approach, the purpose of this work was to assess the extent to which the neurosurgical resections of low-grade glioma affect metacognitive processes and personality traits. First, we showed that frontal lobectomies, both unilateral and bilateral, did not induce metaperceptive impairments despite the established role of the prefrontal cortex in metacognition. Likewise, our results suggest that massive surgical resections did not significantly affect personality traits. However, some of them such as positive schizotypy, and a few behavioral modifications, such as anosognosia, were found to be associated with the disruption of some white matter bundles
7
Yordanova, Yordanka Nikolova. "Un éclairage nouveau sur les bases neurales de la mentalisation : une étude combinant cartographie multimodale et IRM fonctionnelle de repos chez des patients atteints d’un gliome diffus de bas grade." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT052/document.
Анотація:
La mentalisation, ou la capacité d’élaborer des hypothèses sur les états mentaux d’autrui, a fait l’objet de nombreuses études durant les 20 dernières années dans le champ des neurosciences sociales. Toutefois, les bases neurales de cette fonction particulièrement complexe restent mal comprises, notamment en termes de connectivité structurale. Récemment, une organisation anatomo-fonctionnelle en double voie a été proposée. Selon ce modèle, les aspects réflexifs, inférentiels, de la mentalisation seraient sous-tendus par le faisceau cingulaire. Les aspects préréflexifs, identificatoires, seraient médiés, quant à eux, par le complexe faisceau arqué/partie latérale du faisceau longitudinal supérieur (FLS). L’objectif général de ce travail est d’apporter des données originales sur l’organisation anatomo-fonctionnelle du réseau neural impliqué dans la mentalisation basée sur les visages. Pour ce faire, nous avons utilisé comme modèle physiopathologique d’étude le gliome diffus de bas grade. Cette tumeur cérébrale primitive s’avère particulièrement intéressante pour l’étude du rôle de la substance blanche dans la cognition et ce pour deux raisons : (i) les cellules tumorales se propagent préférentiellement le long des fibres blanches ; (ii) l’exérèse chirurgicale est souvent réalisée en condition éveillée avec cartographie fonctionnelle peropératoire pour permettre d’identifier, et ainsi de préserver, les structures fonctionnelles, notamment de substance blanche.Dans une première étude, grâce aux stimulations électriques peropératoires, nous avons pu identifier un vaste réseau cortico-sous-cortical impliqué dans la mentalisation. L’analyse des déconnexions induites par les stimulations de la substance blanche nous a permis de mettre clairement en évidence, et ce pour la première fois, le rôle du faisceau occipito-frontal inférieur (FOFI) tout en confirmant celui du FLS. Dans une deuxième étude, en utilisant des techniques de cartographie lésionnelle chez des patients ayant été opérés, nous avons démontré que les troubles permanents, non compensables, de la mentalisation étaient expliqués par l’atteinte du faisceau arqué. Enfin, dans une dernière étude, en combinant l’imagerie par résonance magnétique fonctionnelle de repos (IRMfr) et les sites corticaux démasqués pendant la chirurgie, nous avons pu générer de véritables cartographies fonctionnelles du réseau cortical de la mentalisation, très similaires à celles observées en imagerie fonctionnelle classique.De façon générale, nos découvertes suggèrent que la mentalisation basée sur les visages reposerait sur l’intégrité d’au moins deux faisceaux associatifs de substance blanche. Elles permettent également de valider l’utilisation combinée de l’IRMfr et des stimulations corticales en tant qu’approche originale pour cartographier les réseaux neurocognitifs.En plus de ces considérations fondamentales, nos résultats ont des implications cliniques, notamment pour la cartographie fonctionnelle peropératoire. Ils permettent en outre de mieux comprendre les pathologies cérébrales caractérisées par un trouble de la mentalisation et une atteinte des voies de substance blancheMentalizing, or the ability of human beings to make assumptions about other people’s mental states, has been the subject of many studies over the last 20 years. The neural bases and especially the white matter connectivity of this complex cognitive function is still poorly understood. Recently, an anatomo-functional organization into two neural pathways has been proposed. According to this model, it is assumed that the reflective, inferential aspects of mentalizing is underpinned by the cingulum. The reflexive, identificatory aspects of mentalizing are thought to be mediated, for their part, by the arcuate fascicle and the lateral part of the superior longitudinal fascicle. The main purpose of this scientific work is to provide original data on the anatomo-functional organization of the neural network involved in the face-based mentalizing. We used as a pathophysiological study model diffuse low-grade gliomas. These primary brain tumors are particularly interesting for the study of the functional role of the white matter for two reasons: (i) the tumor cells propagate preferentially along the white matter fibers; (ii) the surgical resection is often performed in awake condition with intraoperative functional mapping to identify, and thus to preserve functional structures, including the white matter.In our first study, using intraoperative electrical stimulation, we were able to identify a large cortico-subcortical mentalizing network. The analysis of the disconnections induced by the stimulation of the white matter allowed us to clearly highlight, for the first time, the role of the inferior fronto-occipital fascicle. We also confirmed the already established role of the superior longitudinal fascicle in mentalizing. In a second study, using lesion mapping analyses in patients operated on for a diffuse low-grade glioma, we demonstrated that the long-term, non-compensatory mentalizing deficit was explained by the involvement of the arcuate fascicle. Finally, in a third study combining resting-state functional MRI and the cortical sites unmasked during surgery, we were able to identify a large cortical mentalizing networks, which were very similar to those identified by classical task-based functional imaging.In general, our findings suggest that the face-based mentalizing would require the integrity of at least two associative white matter fascicles. They also validate the combined use of resting-state functional MRI and direct cortical stimulations as an original approach to map neurocognitive networks.In addition to these fundamental considerations, our results have also clinical implications, especially regarding the intraoperative functional mapping. They also provide a better understanding of brain pathologies characterized by both mentalizing deficit and white matter impairment
Частини книг з теми "Diffuse Low-Grade Glioma (DLGG)":
1
Mandonnet, Emmanuel, Luc Taillandier, and Hugues Duffau. "From Management of Incidental DLGG to Screening of Silent DLGG." In Diffuse Low-Grade Gliomas in Adults, 729–38. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-55466-2_35.
2
Mandonnet, Emmanuel. "Biomathematical Modeling of DLGG." In Diffuse Low-Grade Gliomas in Adults, 651–64. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-55466-2_31.
3
Duffau, Hugues, and Luc Taillandier. "New Individualized Strategies in DLGG." In Diffuse Low-Grade Gliomas in Adults, 435–43. London: Springer London, 2013. http://dx.doi.org/10.1007/978-1-4471-2213-5_27.
4
Mandonnet, Emmanuel. "Biomathematical Modeling of DLGG Behavior." In Diffuse Low-Grade Gliomas in Adults, 447–55. London: Springer London, 2013. http://dx.doi.org/10.1007/978-1-4471-2213-5_28.
5
Duffau, Hugues. "Interactions Between Diffuse Low-Grade Glioma (DLGG) and Brain Plasticity." In Diffuse Low-Grade Gliomas in Adults, 337–56. London: Springer London, 2013. http://dx.doi.org/10.1007/978-1-4471-2213-5_22.
6
Herbet, Guillaume, and Sylvie Moritz-Gasser. "Functional Rehabilitation in Patients with Diffuse Low-Grade Glioma (DLGG)." In Diffuse Low-Grade Gliomas in Adults, 463–73. London: Springer London, 2013. http://dx.doi.org/10.1007/978-1-4471-2213-5_30.
7
Duffau, Hugues. "Interactions Between Diffuse Low-Grade Glioma (DLGG), Brain Connectome and Neuroplasticity." In Diffuse Low-Grade Gliomas in Adults, 431–65. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-55466-2_22.
8
Mandonnet, Emmanuel. "Dynamics of DLGG and Clinical Implications." In Diffuse Low-Grade Gliomas in Adults, 287–306. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-55466-2_16.
9
Herbet, Guillaume, and Sylvie Moritz-Gasser. "Functional Rehabilitation in Patients with DLGG." In Diffuse Low-Grade Gliomas in Adults, 595–608. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-55466-2_27.
10
Mandonnet, Emmanuel. "Dynamics of DLGG and Clinical Implications." In Diffuse Low-Grade Gliomas in Adults, 249–62. London: Springer London, 2013. http://dx.doi.org/10.1007/978-1-4471-2213-5_17.
Тези доповідей конференцій з теми "Diffuse Low-Grade Glioma (DLGG)":
1
Ben Abdallah, Meriem, Marie Blonski, Sophie Wantz-Mezieres, Yann Gaudeau, Luc Taillandier, and Jean-Marie Moureaux. "Predictive models for diffuse low-grade glioma patients under chemotherapy." In 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2016. http://dx.doi.org/10.1109/embc.2016.7591692.
2
Ben Abdallah, Meriem, Marie Blonski, Sophie Wantz-Mezieres, Yann Gaudeau, Luc Taillandier, and Jean-Marie Moureaux. "Statistical evaluation of manual segmentation of a diffuse low-grade glioma MRI dataset." In 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2016. http://dx.doi.org/10.1109/embc.2016.7591703.
3
Brzenczek, Cyril, Sophie Mezieres, Yann Gaudeau, Marie Blonski, Fabien Rech, Tiphaine Obara, Luc Taillandier, and Jean-Marie Moureaux. "An original MRI-based method to quantify the Diffuse Low-Grade Glioma brain infiltration." In 2020 Tenth International Conference on Image Processing Theory, Tools and Applications (IPTA). IEEE, 2020. http://dx.doi.org/10.1109/ipta50016.2020.9286608.
4
Scheinin, Ilari, Hinke F. van Thuijl, Daoud Sie, Hendrik F. van Essen, Paul P. Eijk, Francois Rustenburg, Ahmed Idbaih, et al. "Abstract 3426: A novel approach to copy number assessment by whole genome sequencing reveals extensive spatial heterogeneity in diffuse low-grade glioma." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-3426.