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BACKGROUND: With expanding neurosurgical options in epilepsy, it is important to characterise each options' risk for postoperative cognitive decline. Here, we characterise how patients' preoperative white matter (WM) networks relates to postoperative memory changes following different epilepsy surgeries. METHODS: Eighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL: n=38) or stereotactic laser amygdalohippocampotomy (SLAH; n=51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of two deep WM tracts (uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF)). RESULTS: Preoperatively, left-lateralised FA of the ILF was associated with higher prose recall (p<0.01). This pattern was not observed for the UF or hippocampus (ps>0.05). Postoperatively, right-lateralised FA of the UF was associated with less decline following left ATL (p<0.05) but not left SLAH (p>0.05), while right-lateralised hippocampal asymmetry was associated with less decline following both left ATL and SLAH (ps<0.05). After accounting for preoperative memory score, age of onset and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (p<0.01). CONCLUSIONS: Asymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline.
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Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal , Hipocampo , Transtornos da Memória , Substância Branca , Humanos , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Masculino , Feminino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Lobectomia Temporal Anterior/efeitos adversos , Hipocampo/cirurgia , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Complicações Pós-Operatórias , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Adulto Jovem , Tonsila do Cerebelo/cirurgia , Tonsila do Cerebelo/patologia , Tonsila do Cerebelo/diagnóstico por imagemRESUMO
INTRODUCTION: Brain injury is common following open heart valve surgery. Carbon dioxide insufflation (CDI) has been proposed to reduce the incidence of brain injury by reducing the number of air microemboli entering the bloodstream in surgery. The CO2 Study will evaluate the efficacy and safety of CDI in patients undergoing planned left-sided open heart valve surgery. METHODS AND ANALYSIS: The CO2 Study is a multicentre, blinded, placebo-controlled, randomised controlled trial. Seven-hundred and four patients aged 50 years and over undergoing planned left-sided heart valve surgery will be recruited to the study, from at least eight UK National Health Service hospitals, and randomised in a 1:1 ratio to receive CDI or medical air insufflation (placebo) in addition to standard de-airing. Insufflation will be delivered at a flow rate of 5 L/min from before the initiation of cardiopulmonary bypass until 10 min after cardiopulmonary bypass weaning. Participants will be followed up until 3 months post-surgery. The primary outcome is acute ischaemic brain injury within 10 days post-surgery based on new brain lesions identified with diffusion-weighted MRI or clinical evidence of permanent brain injury according to the current definition of stroke. ETHICS AND DISSEMINATION: The study was approved by the East Midlands-Nottingham 2 Research Ethics Committee in June 2020 and the Medicines and Healthcare products Regulatory Agency in May 2020. All participants will provide written informed consent prior to undertaking any study assessments. Consent will be obtained by the principal investigator or a delegated member of the research team who has been trained in the study and undergone Good Clinical Practice training. Results will be disseminated through peer-reviewed publications and presentations at national and international meetings. Study participants will be informed of results through study notifications and patient organisations. TRIAL REGISTRATION NUMBER: ISRCTN30671536.
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Lesões Encefálicas , Insuflação , Humanos , Pessoa de Meia-Idade , Idoso , Dióxido de Carbono , Medicina Estatal , Encéfalo , Valvas Cardíacas , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
PURPOSE: Functional MRI (fMRI) has well-established uses to inform risks and plan maximally safe approaches in neurosurgery. In the field of brain tumour surgery, however, fMRI is currently in a state of clinical equipoise due to debate around both its sensitivity and specificity. MATERIALS AND METHODS: In this review, we summarise the role and our experience of fMRI in neurosurgery for gliomas and metastases. We discuss nuances in the conduct and interpretation of fMRI that, based on our practise, most directly impact fMRI's usefulness in the neurosurgical setting. RESULTS: Illustrated examples in which fMRI in our hands directly influences the neurosurgical treatment of brain tumours include evaluating the probability and nature of functional risks, especially for language functions. These presurgical risk assessments, in turn, help to predict the resectability of tumours, select or deselect patients for awake surgery, indicate the need for neurophysiological monitoring and guide the optimal use of intra-operative stimulation mapping. A further emerging application of fMRI is in measuring functional adaptation of functional networks after (partial) surgery, of potential use in the timing of further surgery. CONCLUSIONS: In appropriately selected patients with a clearly defined surgical question, fMRI offers a valuable complementary tool in the pre-surgical evaluation of brain tumours. However, there is a great need for standards in the administration and analysis of fMRI as much as in the techniques that it is commonly evaluated against. Surprisingly little data exists that evaluates the accuracy of fMRI not just against complementary methods, but in terms of its ultimate clinical aim of minimising post-surgical morbidity.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Mapeamento Encefálico/métodos , Vigília , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/cirurgiaRESUMO
INTRODUCTION: Surgery remains the mainstay for treatment of primary glioblastoma, followed by radiotherapy and chemotherapy. Current standard of care during surgery involves the intraoperative use of image-guidance and 5-aminolevulinic acid (5-ALA). There are multiple other surgical adjuncts available to the neuro-oncology surgeon. However, access to, and usage of these varies widely in UK practice, with limited evidence of their use. The aim of this trial is to investigate whether the addition of diffusion tensor imaging (DTI) and intraoperative ultrasound (iUS) to the standard of care surgery (intraoperative neuronavigation and 5-ALA) impacts on deterioration free survival (DFS). METHODS AND ANALYSIS: This is a two-stage, randomised control trial (RCT) consisting of an initial non-randomised cohort study based on the principles of the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) stage-IIb format, followed by a statistically powered randomised trial comparing the addition of DTI and iUS to the standard of care surgery. A total of 357 patients will be recruited for the RCT. The primary outcome is DFS, defined as the time to either 10-point deterioration in health-related quality of life scores from baseline, without subsequent reversal, progressive disease or death. ETHICS AND DISSEMINATION: The trial was registered in the Integrated Research Application System (Ref: 264482) and approved by a UK research and ethics committee (Ref: 20/LO/0840). Results will be published in a peer-reviewed journal. Further dissemination to participants, patient groups and the wider medical community will use a range of approaches to maximise impact. TRIAL REGISTRATION NUMBER: ISRCTN38834571.
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Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Neuronavegação/métodos , Ácido Aminolevulínico , Qualidade de Vida , Ultrassonografia de IntervençãoRESUMO
Objective: To evaluate declarative memory outcomes in medically refractory epilepsy patients who underwent either a highly selective laser ablation of the amygdalohippocampal complex or a conventional open temporal lobe resection. Methods: Post-operative change scores were examined for verbal memory outcome in epilepsy patients who underwent stereotactic laser amygdalohippocampotomy (SLAH: n = 40) or open resection procedures (n = 40) using both reliable change index (RCI) scores and a 1-SD change metric. Results: Using RCI scores, patients undergoing open resection (12/40, 30.0%) were more likely to decline on verbal memory than those undergoing SLAH (2/40 [5.0%], p = 0.0064, Fisher's exact test). Patients with language dominant procedures were much more likely to experience a significant verbal memory decline following open resection (9/19 [47.4%]) compared to laser ablation (2/19 [10.5%], p = 0.0293, Fisher's exact test). 1 SD verbal memory decline frequently occurred in the open resection sample of language dominant temporal lobe patients with mesial temporal sclerosis (8/10 [80.0%]), although it rarely occurred in such patients after SLAH (2/14, 14.3%) (p = 0.0027, Fisher's exact test). Memory improvement occurred significantly more frequently following SLAH than after open resection. Interpretation: These findings suggest that while verbal memory function can decline after laser ablation of the amygdalohippocampal complex, it is better preserved when compared to open temporal lobe resection. Our findings also highlight that the dominant hippocampus is not uniquely responsible for verbal memory. While this is at odds with our simple and common heuristic of the hippocampus in memory, it supports the findings of non-human primate studies showing that memory depends on broader medial and lateral TL regions.
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INTRODUCTION: Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)'s sensitivity to predict morbidity after neurosurgical oncology treatment. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and after awake neurosurgery; (2) evaluate utility of early post-operative DT to predict recovery from post-surgical deficits. METHODS: We retrospectively reviewed our first 100 awake neurosurgery procedures using DT- neuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations. Post-operative DT data, available in 51 patients, were inspected for tract damage. RESULTS: 91 adult brain tumor patients (mean 49.2 years, 43 women) underwent 100 awake surgeries with subcortical stimulation between 2014 and 2019. Sensitivity and specificity of pre-operative DT predictions were 92.2% and 69.2%, varying among tracts. Post-operative deficits occurred after 41 procedures (39%), but were prolonged (> 3 months) in only 4 patients (4%). Post-operative DT in general confirmed surgical preservation of tracts. Post-operative DT anticipated complete recovery in a patient with supplementary motor area syndrome, and indicated infarct-related damage to corticospinal fibers associated with delayed, partial recovery in a second patient. CONCLUSIONS: Pre-operative DT provided very accurate predictions of the spatial location of tracts in relation to a tumor. As expected, however, the presence of a tract did not inform its functional status, resulting in variable DT specificity among individual tracts. While prolonged deficits were rare, DT in the immediate post-operative period offered additional potential to monitor neurological deficits and anticipate recovery potential.
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Imagem de Tensor de Difusão , Vigília , Mapeamento Encefálico , Craniotomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Large individual differences in how brain networks respond to treatment hinder efforts to personalise treatment in neurological conditions. We used a brain network fingerprinting approach to longitudinally track re-organisation of complementary phonological and semantic language networks in 19 patients before and after brain-tumour surgery. Patient task fingerprints were individually compared to normal networks established in 17 healthy controls. Additionally, pre- and post-operative patient fingerprints were directly compared to assess longitudinal network adaptations. We found that task networks remained stable over time in healthy controls, whereas treatment induced reorganisation in 47.4% of patient fluency networks and 15.8% of semantic networks. How networks adapted after surgery was highly unique; a subset of patients (10%) showed 'normalisation' while others (21%) developed newly atypical networks after treatment. The strongest predictor of adaptation of the fluency network was the presence of clinically reported language symptoms. Our findings indicate a tight coupling between processes disrupting performance and neural network adaptation, the patterns of which appear to be both task- and individually-unique. We propose that connectivity fingerprinting offers potential as a clinical marker to track adaptation of specific functional networks across treatment interventions over time.
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Idioma , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Individualidade , Vias Neurais/diagnóstico por imagemRESUMO
PURPOSE: Functional magnetic resonance imaging (fMRI) has an established role in neurosurgical planning; however, ambiguity surrounds the comparative value of resting and task-based fMRI relative to anatomical localization of the sensorimotor cortex. This study was carried out to determine: 1) how often fMRI adds to prediction of motor risks beyond expert neuroradiological review, 2) success rates of presurgical resting and task-based sensorimotor mapping, and 3) the impact of accelerated resting fMRI acquisitions on network detectability. METHODS: Data were collected at 2 centers from 71 patients with a primary brain tumor (31 women; mean age 41.9⯱ 13.9 years) and 14 healthy individuals (6 women; mean age 37.9⯱ 12.7 years). Preoperative 3T MRI included anatomical scans and resting fMRI using unaccelerated (TRâ¯= 3.5â¯s), intermediate (TRâ¯= 1.56â¯s) or high temporal resolution (TRâ¯= 0.72â¯s) sequences. Task fMRI finger tapping data were acquired in 45 patients. Group differences in fMRI reproducibility, spatial overlap and success frequencies were assessed with ttests and χ2-tests. RESULTS: Radiological review identified the central sulcus in 98.6% (70/71) patients. Task-fMRI succeeded in 100% (45/45). Resting fMRI failed to identify a sensorimotor network in up to 10 patients; it succeeded in 97.9% (47/48) of accelerated fMRIs, compared to only 60.9% (14/23) of unaccelerated fMRIs ([Formula: see text](2)â¯= 17.84, pâ¯< 0.001). Of the patients 12 experienced postoperative deterioration, largely predicted by anatomical proximity to the central sulcus. CONCLUSION: The use of fMRI in patients with residual or intact presurgical motor function added value to uncertain anatomical localization in just a single peri-Rolandic glioma case. Resting fMRI showed high correspondence to task localization when acquired with accelerated sequences but offered limited success at standard acquisitions.
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Neoplasias Encefálicas , Glioma , Córtex Sensório-Motor , Adulto , Mapeamento Encefálico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Feminino , Glioma/diagnóstico por imagem , Glioma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Reprodutibilidade dos Testes , Córtex Sensório-Motor/diagnóstico por imagemRESUMO
Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.
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Encéfalo/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Consenso , HumanosRESUMO
OBJECTIVE: Raman spectroscopy is a biophotonic tool that can be used to differentiate between different tissue types. It is nondestructive and no sample preparation is required. The aim of this study was to evaluate the ability of Raman spectroscopy to differentiate between glioma and normal brain when using fresh biopsy samples and, in the case of glioblastomas, to compare the performance of Raman spectroscopy to predict the presence or absence of tumor with that of 5-aminolevulinic acid (5-ALA)-induced fluorescence. METHODS: A principal component analysis (PCA)-fed linear discriminant analysis (LDA) machine learning predictive model was built using Raman spectra, acquired ex vivo, from fresh tissue samples of 62 patients with glioma and 11 glioma-free brain samples from individuals undergoing temporal lobectomy for epilepsy. This model was then used to classify Raman spectra from fresh biopsies from resection cavities after functional guided, supramaximal glioma resection. In cases of glioblastoma, 5-ALA-induced fluorescence at the resection cavity biopsy site was recorded, and this was compared with the Raman spectral model prediction for the presence of tumor. RESULTS: The PCA-LDA predictive model demonstrated 0.96 sensitivity, 0.99 specificity, and 0.99 accuracy for differentiating tumor from normal brain. Twenty-three resection cavity biopsies were taken from 8 patients after supramaximal resection (6 glioblastomas, 2 oligodendrogliomas). Raman spectroscopy showed 1.00 sensitivity, 1.00 specificity, and 1.00 accuracy for predicting tumor versus normal brain in these samples. In the glioblastoma cases, where 5-ALA-induced fluorescence was used, the performance of Raman spectroscopy was significantly better than the predictive value of 5-ALA-induced fluorescence, which showed 0.07 sensitivity, 1.00 specificity, and 0.24 accuracy (p = 0.0009). CONCLUSIONS: Raman spectroscopy can accurately classify fresh tissue samples into tumor versus normal brain and is superior to 5-ALA-induced fluorescence. Raman spectroscopy could become an important intraoperative tool used in conjunction with 5-ALA-induced fluorescence to guide extent of resection in glioma surgery.
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BACKGROUND: The interhemispheric fissure provides a natural surgical corridor to access tumors of the deep medial surface of the brain. Conventional microscopic approaches to these tumors are limited by the narrow width of the interhemispheric fissure and need for retraction of brain tissue or traversing overlying cortex. Over the last decade, the endoscope has been used to improve visualization of the operative field in neurosurgery, with benefits in terms of surgical ergonomics and extent of tumor resections. In the context of the interhemispheric fissure, an endoscopic approach may improve visualization of some tumors by providing a brighter, more divergent light source at depth and by enabling the operator to inspect around curved structures (e.g., corpus callosum). CASE DESCRIPTION: In this report, we present a series of 5 cases with tumors at various locations along the anteroposterior extent of the interhemispheric fissure that were resected using an endoscopic ipsilateral interhemispheric approach. CONCLUSIONS: The endoscopic ipsilateral interhemispheric approach is an effective and versatile approach to resection of selected deep medial brain tumors extending anteriorly from the genu of the corpus callosum to the splenium. It has notable advantages over the microscope and can be considered a useful adjunct in the surgeon's armamentarium.
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Neoplasias Encefálicas/cirurgia , Neuroendoscopia/métodos , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Astrocitoma/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Carcinoma/cirurgia , Corpo Caloso/cirurgia , Feminino , Ganglioglioma/cirurgia , Germinoma/cirurgia , Glioblastoma/cirurgia , Giro do Cíngulo/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Meningioma/cirurgia , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Stroke is one of the most common causes of death and a leading factor of disability in adults worldwide. It occurs when the blood supply to part of the brain is significantly reduced, potentially leading to the formation of brain oedema. Owing to the rigid nature of the skull, brain expansion results in the shifting of tissue structure, often captured by measurement of the midline shift (MLS). Clinically, MLS has been used in practice as an indication of stroke severity, potential tissue damage and as a way to assess whether decompressive surgery should be performed. However, a growing body of research points towards limitations in such predictive ability. Inspired by the recent progress made in traumatic brain injury simulations, in silico experiments appear as the ideal candidate to elucidate stroke consequences on brain tissues, e.g., morphological changes, in particular in the overarching context of computer model assisted clinical decision making support. To this end, two biologically-informed finite element head models, human and rat, were constructed to support such analysis. The main components of the models include magnetic resonance imaging-derived grey matter, white matter, cerebrospinal fluid and skull, while the human head model also includes the vasculature, additional cerebral components and axonal tractography. Constitutive models representing the mechanical behaviour of each component account in particular for the behaviour of brain tissues during the swelling process accompanying oedema development. The rat model was leveraged for the calibration of the swelling parameters, in turn used for the simulation of human stroke. Human oedema development as a result of stroke was simulated at three frequent locations: basal ganglia, fronto-opercular/anterior insula and temporo-parietal. All three cases exhibit a quadratic MLS evolution with time with the basal ganglia and temporo-parietal showing the largest and smallest values, respectively, at any given time. A proposed injury criterion for axonal tract damage was shown to be larger in the temporo-parietal case. Taken together, these results point towards i) the importance of considering stroke location when using the MLS as an indication of stroke severity, and ii) the potential lack of correlation between MLS value and tissue damage. Ultimately, we propose an in silico methodology that may hold promise in predicting stroke evolution based on an estimate of MLS and stroke location at a given time.
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Simulação por Computador , Análise de Elementos Finitos , Cabeça , AVC Isquêmico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , AVC Isquêmico/patologia , RatosRESUMO
Selective laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for medial temporal lobe epilepsy. Visual field deficits (VFDs) are a significant potential complication. The objective of this study was to determine the relationship between VFDs and potential mechanisms of injury to the optic radiations and lateral geniculate nucleus. We performed a retrospective cross-sectional analysis of 3 patients (5.2%) who developed persistent VFDs after SLAH within our larger series (n = 58), 15 healthy individuals and 10 SLAH patients without visual complications. Diffusion tractography was used to evaluate laser catheter penetration of the optic radiations. Using a complementary approach, we evaluated evidence for focal microstructural tissue damage within the optic radiations and lateral geniculate nucleus. Overablation and potential heat radiation were assessed by quantifying ablation and choroidal fissure CSF volumes as well as energy deposited during SLAH.SLAH treatment parameters did not distinguish VFD patients. Atypically high overlap between the laser catheter and optic radiations was found in 1/3 VFD patients and was accompanied by focal reductions in fractional anisotropy where the catheter entered the lateral occipital white matter. Surprisingly, lateral geniculate tissue diffusivity was abnormal following, but also preceding, SLAH in patients who subsequently developed a VFD (all p = 0.005).In our series, vision-related complications following SLAH, which appear to occur less frequently than following open temporal lobe -surgery, were not directly explained by SLAH treatment parameters. Instead, our data suggest that variations in lateral geniculate structure may influence susceptibility to indirect heat injury from transoccipital SLAH.
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Tonsila do Cerebelo/cirurgia , Hipocampo/cirurgia , Terapia a Laser/efeitos adversos , Complicações Pós-Operatórias/etiologia , Técnicas Estereotáxicas/efeitos adversos , Transtornos da Visão/etiologia , Adolescente , Adulto , Idoso , Tonsila do Cerebelo/diagnóstico por imagem , Estudos Transversais , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Feminino , Seguimentos , Hipocampo/diagnóstico por imagem , Humanos , Terapia a Laser/tendências , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Psicocirurgia/efeitos adversos , Psicocirurgia/tendências , Estudos Retrospectivos , Fatores de Risco , Técnicas Estereotáxicas/tendências , Transtornos da Visão/diagnóstico por imagem , Campos Visuais/fisiologia , Adulto JovemRESUMO
The occurrence of wide-scale neuroplasticity in the injured human brain raises hopes for biomarkers to guide personalised treatment. At the individual level, functional reorganisation has proven challenging to quantify using current techniques that are optimised for population-based analyses. In this cross-sectional study, we acquired functional MRI scans in 44 patients (22 men, 22 women, mean age: 39.4⯱â¯14â¯years) with a language-dominant hemisphere brain tumour prior to surgery and 23 healthy volunteers (11 men, 12 women, mean age: 36.3⯱â¯10.9â¯years) during performance of a verbal fluency task. We applied a recently developed approach to characterise the normal range of functional connectivity patterns during task performance in healthy controls. Next, we statistically quantified differences from the normal in individual patients and evaluated factors driving these differences. We show that the functional connectivity of brain regions involved in language fluency identifies "fingerprints" of brain plasticity in individual patients, not detected using standard task-evoked analyses. In contrast to healthy controls, patients with a tumour in their language dominant hemisphere showed highly variable fingerprints that uniquely distinguished individuals. Atypical fingerprints were influenced by tumour grade and tumour location relative to the typical fluency-activated network. Our findings show how alterations in brain networks can be visualised and statistically quantified from connectivity fingerprints in individual brains. We propose that connectivity fingerprints offer a statistical metric of individually-specific network organisation through which behaviourally-relevant adaptations could be formally quantified and monitored across individuals, treatments and time.
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Mapeamento Encefálico/tendências , Encéfalo/diagnóstico por imagem , Idioma , Imageamento por Ressonância Magnética/tendências , Rede Nervosa/diagnóstico por imagem , Plasticidade Neuronal , Adulto , Idoso , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Estudos Transversais , Feminino , Humanos , Individualidade , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Estudos ProspectivosRESUMO
The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acids, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional ¹H MRS-detectable differences between IDH1 and IDH2 mutations, and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 37 ± 11, 13 males) were recruited for magnetic resonance spectroscopy (MRS) using semi-localization by adiabatic selective refocusing pulse sequence at an ultra-high-field (7T). For 20 patients, the tumor mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n = 15) and IDH2 (n = 5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.48 ± 1.01vs.0.72 ± 0.38, Pc < 0.001) and myo-Inositol/tCho (2.70 ± 0.90 vs. 1.46 ± 0.51, Pc = 0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show the improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.
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BACKGROUND: Surgical access to the temporal lobe is complex with many eloquent white fiber tracts, requiring careful preoperative surgical planning. Many microsurgical approaches to the temporal lobes are described, each with their own disadvantages. The adoption of the endoscope in neurosurgery has increased the options available when treating these difficult access tumors. We present our experience of a novel, minimally invasive, endoscopic approach to resect temporal lobe tumors. METHODS: All patients undergoing endoscopic temporal lobe tumor resection between December 1, 2011 and December 1, 2017, with a single surgeon, were included. Tumors were resected through a minicraniotomy using a high-definition rigid endoscope with a 0- and 30-degree viewing angle. Bimanual resection was performed using standard microsurgical technique. RESULTS: There were 45 patients (22 men and 23 women) with a mean age of 53 years. There were 23 (51%) glioblastoma multiforme, 11 (24%) metastases, 7 (16%) astrocytoma, 3 (7%) anaplastic astrocytoma, and 1 (2%) World Health Organization grade I glioneuronal tumor. In 82.2% of cases (37/45), >95% resection was achieved and 42.2% (19/45) of patients achieving gross total resection. CONCLUSIONS: The endoscope has a role in temporal lobe intraparenchymal tumor surgery, especially in 3 illustrative scenarios: 1) medial temporal, parahippocampal-gyrus low-grade nonenhancing gliomas, 2) subcortical high-grade glioma and metastases medial to the sagittal stratum, and 3) recurrent gliomas with cystic resection cavity. The endoscope offers a safe and useful adjunct to the surgeons' armamentarium in brain tumor surgery. A minimally invasive approach also reduces surgical morbidity and length of stay.
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Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Neuroendoscopia/métodos , Lobo Temporal/cirurgia , Adulto , Idoso , Astrocitoma/cirurgia , Neoplasias Encefálicas/secundário , Craniotomia/métodos , Feminino , Glioblastoma/cirurgia , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Magnetic resonance spectroscopic imaging (MRSI) is a promising technique in both experimental and clinical settings. However, to date, MRSI has been hampered by prohibitively long acquisition times and artifacts caused by subject motion and hardware-related frequency drift. In the present study, we demonstrate that density weighted concentric ring trajectory (DW-CRT) k-space sampling in combination with semi-LASER excitation and metabolite-cycling enables high-resolution MRSI data to be rapidly acquired at 3 Tesla. Single-slice full-intensity MRSI data (short echo time (TE) semi-LASER TE = 32 ms) were acquired from 6 healthy volunteers with an in-plane resolution of 5 × 5 mm in 13 min 30 sec using this approach. Using LCModel analysis, we found that the acquired spectra allowed for the mapping of total N-acetylaspartate (median Cramer-Rao Lower Bound [CRLB] = 3%), glutamate+glutamine (8%), and glutathione (13%). In addition, we demonstrate potential clinical utility of this technique by optimizing the TE to detect 2-hydroxyglutarate (long TE semi-LASER, TE = 110 ms), to produce relevant high-resolution metabolite maps of grade III IDH-mutant oligodendroglioma in a single patient. This study demonstrates the potential utility of MRSI in the clinical setting at 3 Tesla.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Glutaratos/análise , Espectroscopia de Ressonância Magnética/métodos , Adulto , Idoso , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Feminino , Humanos , MasculinoRESUMO
Abnormally high levels of the 'oncometabolite' 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2-HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2-HG detection. To combat this, several groups have proposed MRS methods at ultra-high field (≥7 T) where theoretical increases in signal-to-noise ratio and spectral resolution could improve 2-HG detection. Long echo time (long-TE) semi-localization by adiabatic selective refocusing (semi-LASER) (TE = 110 ms) is a promising method for improved 2-HG detection in vivo at either 3 or 7 T owing to the use of broad-band adiabatic localization. Using previously published semi-LASER methods at 3 and 7 T, this study directly compares the detectability of 2-HG in phantoms and in vivo across nine patients. Cramér-Rao lower bounds (CRLBs) of 2-HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) (p = 0.0019), yet were larger at 7 T in an IDH wild-type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2-HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ-aminobutyric acid (GABA) and 2-HG (p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2-HG detection using long-TE acquisition at 7 T may allow for more rapid estimation of 2-HG (within a few spectral averages) together with other associated metabolic markers in glioma.