RESUMEN
Pediatric brain and spinal cancers remain the leading cause of cancer-related death in children. Advancements in clinical decision-support in pediatric neuro-oncology utilizing the wealth of radiology imaging data collected through standard care, however, has significantly lagged other domains. Such data is ripe for use with predictive analytics such as artificial intelligence (AI) methods, which require large datasets. To address this unmet need, we provide a multi-institutional, large-scale pediatric dataset of 23,101 multi-parametric MRI exams acquired through routine care for 1,526 brain tumor patients, as part of the Children's Brain Tumor Network. This includes longitudinal MRIs across various cancer diagnoses, with associated patient-level clinical information, digital pathology slides, as well as tissue genotype and omics data. To facilitate downstream analysis, treatment-naïve images for 370 subjects were processed and released through the NCI Childhood Cancer Data Initiative via the Cancer Data Service. Through ongoing efforts to continuously build these imaging repositories, our aim is to accelerate discovery and translational AI models with real-world data, to ultimately empower precision medicine for children.
RESUMEN
Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified. There were 1800 features extracted from T2- and contrast-enhanced T1-weighted preoperative MRI scans. A two-stage sequential classifier was designed-one that first identifies non-wingless (WNT) and non-sonic hedgehog (SHH) MB and then differentiates therapeutically relevant WNT from SHH. Further, a classifier that distinguishes high-risk group 3 from group 4 MB was developed. An independent, binary subgroup analysis was conducted to uncover radiomics features unique to infantile versus childhood SHH subgroups. The best-performing models from six candidate classifiers were selected, and performance was measured on holdout test sets. CIs were obtained by bootstrapping the test sets for 2000 random samples. Model accuracy score was compared with the no-information rate using the Wald test. Results The study cohort comprised 263 patients (mean age ± SD at diagnosis, 87 months ± 60; 166 boys). A two-stage classifier outperformed a single-stage multiclass classifier. The combined, sequential classifier achieved a microaveraged F1 score of 88% and a binary F1 score of 95% specifically for WNT. A group 3 versus group 4 classifier achieved an area under the receiver operating characteristic curve of 98%. Of the Image Biomarker Standardization Initiative features, texture and first-order intensity features were most contributory across the molecular subgroups. Conclusion An MRI-based machine learning decision path allowed identification of the four clinically relevant molecular pediatric medulloblastoma subgroups. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chaudhary and Bapuraj in this issue.
Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Adolescente , Neoplasias Cerebelosas/diagnóstico por imagen , Neoplasias Cerebelosas/genética , Niño , Preescolar , Femenino , Proteínas Hedgehog/genética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Meduloblastoma/diagnóstico por imagen , Meduloblastoma/genética , Estudios RetrospectivosRESUMEN
BACKGROUND: Cerebrovascular reserve (CVR) inversely correlates with stroke risk in children with Moyamoya disease and may be improved by revascularization surgery. We hypothesized that acetazolamide-challenged arterial spin labeling MR perfusion quantifies augmentation of CVR achieved by revascularization and correlates with currently accepted angiographic scoring criteria. METHODS: We retrospectively identified pediatric patients with Moyamoya disease or syndrome who received cerebral revascularization at ≤18 years of age between 2012 and 2019 at our institution. Using acetazolamide-challenged arterial spin labeling, we compared postoperative CVR to corresponding preoperative values and to postoperative perfusion outcomes classified by Matsushima grading. RESULTS: In this cohort, 32 patients (17 males) with Moyamoya underwent 29 direct and 16 indirect extracranial-intracranial bypasses at a median 9.7 years of age (interquartile range, 7.6-15.7). Following revascularization, median CVR increased within the ipsilateral middle cerebral artery territory (6.9 mL/100 g per minute preoperatively versus 16.5 mL/100 g per minute postoperatively, P<0.01). No differences were observed in the ipsilateral anterior cerebral artery (P=0.13) and posterior cerebral artery (P=0.48) territories. Postoperative CVR was higher in the ipsilateral middle cerebral artery territories of patients who achieved Matsushima grade A perfusion, in comparison to those with grades B or C (25.8 versus 17.5 mL, P=0.02). The method of bypass (direct or indirect) did not alter relative increases in CVR (8 versus 3.8 mL/100 g per minute, P=0.7). CONCLUSIONS: Acetazolamide-challenged arterial spin labeling noninvasively quantifies augmentation of CVR following surgery for Moyamoya disease and syndrome.
Asunto(s)
Revascularización Cerebral , Enfermedad de Moyamoya , Acetazolamida , Revascularización Cerebral/efectos adversos , Revascularización Cerebral/métodos , Circulación Cerebrovascular , Niño , Femenino , Humanos , Masculino , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/cirugía , Estudios Retrospectivos , Marcadores de SpinRESUMEN
BACKGROUND: The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB. METHODS: We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers. RESULTS: For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (P < .0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (P = .002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86. CONCLUSIONS: We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.
Asunto(s)
Ependimoma , Ependimoma/diagnóstico por imagen , Ependimoma/genética , Ependimoma/patología , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Clinicians and machine classifiers reliably diagnose pilocytic astrocytoma (PA) on magnetic resonance imaging (MRI) but less accurately distinguish medulloblastoma (MB) from ependymoma (EP). One strategy is to first rule out the most identifiable diagnosis. OBJECTIVE: To hypothesize a sequential machine-learning classifier could improve diagnostic performance by mimicking a clinician's strategy of excluding PA before distinguishing MB from EP. METHODS: We extracted 1800 total Image Biomarker Standardization Initiative (IBSI)-based features from T2- and gadolinium-enhanced T1-weighted images in a multinational cohort of 274 MB, 156 PA, and 97 EP. We designed a 2-step sequential classifier - first ruling out PA, and next distinguishing MB from EP. For each step, we selected the best performing model from 6-candidate classifier using a reduced feature set, and measured performance on a holdout test set with the microaveraged F1 score. RESULTS: Optimal diagnostic performance was achieved using 2 decision steps, each with its own distinct imaging features and classifier method. A 3-way logistic regression classifier first distinguished PA from non-PA, with T2 uniformity and T1 contrast as the most relevant IBSI features (F1 score 0.8809). A 2-way neural net classifier next distinguished MB from EP, with T2 sphericity and T1 flatness as most relevant (F1 score 0.9189). The combined, sequential classifier was with F1 score 0.9179. CONCLUSION: An MRI-based sequential machine-learning classifiers offer high-performance prediction of pediatric posterior fossa tumors across a large, multinational cohort. Optimization of this model with demographic, clinical, imaging, and molecular predictors could provide significant advantages for family counseling and surgical planning.
Asunto(s)
Neoplasias Cerebelosas , Ependimoma , Neoplasias Infratentoriales , Meduloblastoma , Niño , Humanos , Neoplasias Infratentoriales/diagnóstico por imagen , Imagen por Resonancia Magnética , Meduloblastoma/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) are lethal pediatric brain tumors. Presently, MRI is the mainstay of disease diagnosis and surveillance. We identify clinically significant computational features from MRI and create a prognostic machine learning model. METHODS: We isolated tumor volumes of T1-post-contrast (T1) and T2-weighted (T2) MRIs from 177 treatment-naïve DIPG patients from an international cohort for model training and testing. The Quantitative Image Feature Pipeline and PyRadiomics was used for feature extraction. Ten-fold cross-validation of least absolute shrinkage and selection operator Cox regression selected optimal features to predict overall survival in the training dataset and tested in the independent testing dataset. We analyzed model performance using clinical variables (age at diagnosis and sex) only, radiomics only, and radiomics plus clinical variables. RESULTS: All selected features were intensity and texture-based on the wavelet-filtered images (3 T1 gray-level co-occurrence matrix (GLCM) texture features, T2 GLCM texture feature, and T2 first-order mean). This multivariable Cox model demonstrated a concordance of 0.68 (95% CI: 0.61-0.74) in the training dataset, significantly outperforming the clinical-only model (C = 0.57 [95% CI: 0.49-0.64]). Adding clinical features to radiomics slightly improved performance (C = 0.70 [95% CI: 0.64-0.77]). The combined radiomics and clinical model was validated in the independent testing dataset (C = 0.59 [95% CI: 0.51-0.67], Noether's test P = .02). CONCLUSIONS: In this international study, we demonstrate the use of radiomic signatures to create a machine learning model for DIPG prognostication. Standardized, quantitative approaches that objectively measure DIPG changes, including computational MRI evaluation, could offer new approaches to assessing tumor phenotype and serve a future role for optimizing clinical trial eligibility and tumor surveillance.
RESUMEN
The authors describe the use of the Gigli saw for craniectomy in minimal access surgery to address sagittal craniosynostosis. This modification allows for supine positioning and avoidance of potential brain compression with endoscopic instruments, and provides visually clear, safe, and facile removal of the fused suture and surrounding calvaria. The video can be found here: https://vimeo.com/511568750.
RESUMEN
OBJECTIVE: Imaging evaluation of the cerebral ventricles is important for clinical decision-making in pediatric hydrocephalus. Although quantitative measurements of ventricular size, over time, can facilitate objective comparison, automated tools for calculating ventricular volume are not structured for clinical use. The authors aimed to develop a fully automated deep learning (DL) model for pediatric cerebral ventricle segmentation and volume calculation for widespread clinical implementation across multiple hospitals. METHODS: The study cohort consisted of 200 children with obstructive hydrocephalus from four pediatric hospitals, along with 199 controls. Manual ventricle segmentation and volume calculation values served as "ground truth" data. An encoder-decoder convolutional neural network architecture, in which T2-weighted MR images were used as input, automatically delineated the ventricles and output volumetric measurements. On a held-out test set, segmentation accuracy was assessed using the Dice similarity coefficient (0 to 1) and volume calculation was assessed using linear regression. Model generalizability was evaluated on an external MRI data set from a fifth hospital. The DL model performance was compared against FreeSurfer research segmentation software. RESULTS: Model segmentation performed with an overall Dice score of 0.901 (0.946 in hydrocephalus, 0.856 in controls). The model generalized to external MR images from a fifth pediatric hospital with a Dice score of 0.926. The model was more accurate than FreeSurfer, with faster operating times (1.48 seconds per scan). CONCLUSIONS: The authors present a DL model for automatic ventricle segmentation and volume calculation that is more accurate and rapid than currently available methods. With near-immediate volumetric output and reliable performance across institutional scanner types, this model can be adapted to the real-time clinical evaluation of hydrocephalus and improve clinician workflow.
Asunto(s)
Inteligencia Artificial , Ventrículos Cerebrales/diagnóstico por imagen , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/diagnóstico , Adolescente , Niño , Preescolar , Estudios de Cohortes , Aprendizaje Profundo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Recién Nacido , Imagen por Resonancia Magnética/métodos , Masculino , Modelos Teóricos , Redes Neurales de la Computación , Programas Informáticos , Adulto JovenRESUMEN
Paediatric low-grade gliomas (also known as pLGG) are the most common type of CNS tumours in children. In general, paediatric low-grade gliomas show clinical and biological features that are distinct from adult low-grade gliomas, and the developing paediatric brain is more susceptible to toxic late effects of the tumour and its treatment. Therefore, response assessment in children requires additional considerations compared with the adult Response Assessment in Neuro-Oncology criteria. There are no standardised response criteria in paediatric clinical trials, which makes it more difficult to compare responses across studies. The Response Assessment in Pediatric Neuro-Oncology working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop consensus recommendations for response assessment in paediatric low-grade gliomas. Final recommendations were based on literature review, current practice, and expert opinion of working group members. Consensus recommendations include imaging response assessments, with additional guidelines for visual functional outcomes in patients with optic pathway tumours. As with previous consensus recommendations, these recommendations will need to be validated in prospective clinical trials.
Asunto(s)
Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/terapia , Determinación de Punto Final/normas , Glioma/diagnóstico por imagen , Glioma/terapia , Neuroimagen/normas , Edad de Inicio , Neoplasias del Sistema Nervioso Central/epidemiología , Neoplasias del Sistema Nervioso Central/patología , Niño , Consenso , Femenino , Glioma/epidemiología , Glioma/patología , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Clasificación del Tumor , Imagen de Perfusión/normas , Tomografía de Emisión de Positrones/normas , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del Tratamiento , Carga TumoralRESUMEN
OBJECTIVE: While conventional imaging can readily identify ventricular enlargement in hydrocephalus, structural changes that underlie microscopic tissue injury might be more difficult to capture. MRI-based diffusion tensor imaging (DTI) uses properties of water motion to uncover changes in the tissue microenvironment. The authors hypothesized that DTI can identify alterations in optic nerve microstructure in children with hydrocephalus. METHODS: The authors retrospectively reviewed 21 children (< 18 years old) who underwent DTI before and after neurosurgical intervention for acute obstructive hydrocephalus from posterior fossa tumors. Their optic nerve quantitative DTI metrics of mean diffusivity (MD) and fractional anisotropy (FA) were compared to those of 21 age-matched healthy controls. RESULTS: Patients with hydrocephalus had increased MD and decreased FA in bilateral optic nerves, compared to controls (p < 0.001). Normalization of bilateral optic nerve MD and FA on short-term follow-up (median 1 day) after neurosurgical intervention was observed, as was near-complete recovery of MD on long-term follow-up (median 1.8 years). CONCLUSIONS: DTI was used to demonstrate reversible alterations of optic nerve microstructure in children presenting acutely with obstructive hydrocephalus. Alterations in optic nerve MD and FA returned to near-normal levels on short- and long-term follow-up, suggesting that surgical intervention can restore optic nerve tissue microstructure. This technique is a safe, noninvasive imaging tool that quantifies alterations of neural tissue, with a potential role for evaluation of pediatric hydrocephalus.
Asunto(s)
Imagen de Difusión Tensora/métodos , Hidrocefalia/diagnóstico por imagen , Neuroimagen/métodos , Nervio Óptico/diagnóstico por imagen , Enfermedad Aguda , Adolescente , Anisotropía , Estudios de Casos y Controles , Pérdida de Líquido Cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Hidrocefalia/etiología , Hidrocefalia/cirugía , Lactante , Neoplasias Infratentoriales/complicaciones , Neoplasias Infratentoriales/cirugía , Masculino , Meduloblastoma/complicaciones , Meduloblastoma/cirugía , Nervio Óptico/patología , Estudios Retrospectivos , Derivación VentriculoperitonealRESUMEN
Gliomas are a heterogeneous group of tumors with evolving classification based on genotype. Isocitrate dehydrogenase (IDH) mutation is an early event in the formation of some diffuse gliomas, and is the best understood mechanism of their epigenetic dysregulation. Glioblastoma may evolve from lower-grade lesions with IDH mutations, or arise independently from copy number changes in platelet-derived growth factor receptor alpha (PDGFRA) and phosphatase and tensin homolog (PTEN). Several molecular subtypes of glioblastoma arise from a common proneural precursor with a tendency toward transition to a mesenchymal subtype. Following oncogenic transformation, gliomas escape growth arrest through a distinct step of aberrant telomere reverse transcriptase (TERT) expression, or mutations in either alpha thalassemia/mental retardation syndrome (ATRX) or death-domain associated protein (DAXX) genes. Metabolic reprogramming allows gliomas to thrive in harsh microenvironments such as hypoxia, acidity, and nutrient depletion, which contribute to tumor initiation, maintenance, and treatment resistance.
Asunto(s)
Neoplasias Encefálicas/patología , Glioblastoma/patología , Glioma/patología , Reprogramación Celular , Humanos , Isocitrato Deshidrogenasa/genética , Mutación , Fosfohidrolasa PTEN/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Telomerasa/genética , Microambiente Tumoral , Proteína Nuclear Ligada al Cromosoma X/genéticaRESUMEN
OBJECTIVE: Moyamoya disease is a dynamic cerebrovascular condition that often requires vascular surveillance. Arterial spin labeling (ASL) is an MR perfusion method that is increasingly used for stroke and other various neurovascular pathologies. Unlike perfusion-weighted MRI, ASL uses endogenous water molecules for signal and therefore obviates gadolinium use; and provides direct, not relative, quantitative cerebral blood flow (CBF) measures. Presently, the potential role of ASL for evaluating postoperative pediatric moyamoya patients is relatively unexplored. This study investigated the role for ASL in evaluating cerebral hemodynamic changes in children who underwent revascularization surgery. METHODS: This retrospective study examined 15 consecutive pediatric patients with moyamoya disease (n = 7) or moyamoya syndrome (n = 8) presenting between 2010 and 2014 who underwent revascularization and in whom 3T ASL was performed pre- and postoperatively. Postoperative MRI at least 3 months after revascularization procedure was used for analysis. Quantitative CBF in various vascular territories was interrogated: anterior, middle, and posterior cerebral arteries, and basal ganglia supplied by the lenticulostriate collaterals, resulting in evaluation of 20 brain regions. RESULTS: After revascularization, CBF in the high middle cerebral artery territory significantly increased (p = 0.0059), accompanied by a decrease in CBF to the ipsilateral lenticulostriate-supplied basal ganglia (p = 0.0053). No perfusion changes occurred in the remaining cerebral vascular territories after surgery. CONCLUSIONS: ASL-based quantitative CBF showed improved cerebral perfusion to the middle cerebral artery territory after revascularization in children with both moyamoya syndrome and disease. Reduced perfusion to the basal ganglia might reflect pruning of the lenticulostriate collaterals, potentially from effects of revascularization. ASL can quantitatively evaluate hemodynamic changes in children with moyamoya after revascularization, and it may be a useful adjunct to routine clinical MRI surveillance.
Asunto(s)
Arterias Cerebrales/fisiopatología , Revascularización Cerebral/métodos , Circulación Cerebrovascular/fisiología , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/cirugía , Marcadores de Spin , Adolescente , Angiografía de Substracción Digital , Angiografía Cerebral , Arterias Cerebrales/diagnóstico por imagen , Niño , Estudios de Cohortes , Femenino , Humanos , Imagenología Tridimensional , Angiografía por Resonancia Magnética , MasculinoRESUMEN
KIAA1549-BRAF is the most frequently identified genetic mutation in sporadic pilocytic astrocytoma (PA), creating a fusion BRAF (f-BRAF) protein with increased BRAF activity. Fusion-BRAF-expressing neural stem cells (NSCs) exhibit increased cell growth and can generate glioma-like lesions following injection into the cerebella of naïve mice. Increased Iba1+ monocyte (microglia) infiltration is associated with murine f-BRAF-expressing NSC-induced glioma-like lesion formation, suggesting that f-BRAF-expressing NSCs attract microglia to establish a microenvironment supportive of tumorigenesis. Herein, we identify Ccl2 as the chemokine produced by f-BRAF-expressing NSCs, which is critical for creating a permissive stroma for gliomagenesis. In addition, f-BRAF regulation of Ccl2 production operates in an ERK- and NFκB-dependent manner in cerebellar NSCs. Finally, Ccr2-mediated microglia recruitment is required for glioma-like lesion formation in vivo, as tumor do not form in Ccr2-deficient mice following f-BRAF-expressing NSC injection. Collectively, these results demonstrate that f-BRAF expression creates a supportive tumor microenvironment through NFκB-mediated Ccl2 production and microglia recruitment.
Asunto(s)
Quimiocina CCL2/biosíntesis , Expresión Génica , FN-kappa B/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Proteínas de Fusión Oncogénica/genética , Microambiente Tumoral/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones , Ratones Transgénicos , Neoplasias/patologíaRESUMEN
BACKGROUND: Moyamoya disease causes progressive occlusion of the supraclinoidal internal carotid artery, and middle, anterior, and less frequently the posterior cerebral arteries, carrying the risk of stroke. Blood flow is often partially reconstituted by compensatory moyamoya collaterals and sometimes the posterior circulation. Cerebral revascularization can further augment blood flow. These changes to blood flow within the cerebral vessels, however, are not well characterized. OBJECTIVE: To evaluate blood flow changes resulting from the disease process and revascularization surgery using quantitative magnetic resonance angiography with noninvasive optimal vessel analysis (NOVA). METHODS: We retrospectively analyzed 190 preoperative and postoperative imaging scans in 66 moyamoya patients after revascularization surgery. Images were analyzed for blood flow using NOVA and compared with preoperative angiographic staging and postoperative blood flow. Blood flow rates within superficial temporal artery grafts were compared based on angiographic evidence of patency. RESULTS: Diseased vessels had lower blood flow, correlating with angiographic staging. Flow in posterior cererbal and basilar arteries increased with disease severity, particularly when both the anterior and middle cerebral arteries were occluded. Basilar artery flow and ipsilateral internal carotid artery flow decreased after surgery. Flow rates were different between angiographically robust and poor direct bypass grafts, as well as between robust and patent grafts. CONCLUSION: Preoperative changes in cerebral vessel flow as measured by NOVA correlated with angiographic disease progression. NOVA demonstrated that preoperative augmentation of the posterior circulation decreased after surgery. This report is the first to quantify the shift in collateral supply from the posterior circulation to the bypass graft.
Asunto(s)
Revascularización Cerebral/métodos , Angiografía por Resonancia Magnética/métodos , Enfermedad de Moyamoya/diagnóstico por imagen , Adulto , Circulación Cerebrovascular/fisiología , Circulación Colateral/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. STUDY DESIGN: We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure. RESULTS: Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P?.05), whereas patients with PA (all treated with surgery alone) had normal CBF. ADC was decreased specifically in the hippocampus and amygdala of patients with MB and within the amygdala of patients with PA but otherwise remained normal after therapy. In the patients with tumor previously evaluated for IQ, regional ADC, but not CBF, correlated with IQ (R2?=?0.33-0.75). CONCLUSIONS: The treatment for MB, but not PA, was associated with globally reduced CBF. Treatment in both tumor types was associated with diffusion abnormalities of the mesial temporal lobe structures. Despite significant perfusion abnormalities in patients with MB, diffusion, but not perfusion, correlated with cognitive outcomes.
Asunto(s)
Encéfalo/patología , Circulación Cerebrovascular/fisiología , Neoplasias Infratentoriales/fisiopatología , Adolescente , Astrocitoma/fisiopatología , Astrocitoma/terapia , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Neoplasias Infratentoriales/terapia , Imagen por Resonancia Magnética , Masculino , Meduloblastoma/fisiopatología , Meduloblastoma/terapia , Pruebas Neuropsicológicas , Flujo Sanguíneo Regional/fisiología , Estudios Retrospectivos , Adulto JovenRESUMEN
Intraoperative neurophysiological monitoring during endoscopic, endonasal approaches to the skull base is both feasible and safe. Numerous reports have recently emerged from the literature evaluating the efficacy of different neuromonitoring tests during endonasal procedures, making them relatively well-studied. The authors report on a comprehensive, multimodality approach to monitoring the functional integrity of at risk nervous system structures, including the cerebral cortex, brainstem, cranial nerves, corticospinal tract, corticobulbar tract, and the thalamocortical somatosensory system during endonasal surgery of the skull base. The modalities employed include electroencephalography, somatosensory evoked potentials, free-running and electrically triggered electromyography, transcranial electric motor evoked potentials, and auditory evoked potentials. Methodological considerations as well as benefits and limitations are discussed. The authors argue that, while individual modalities have their limitations, multimodality neuromonitoring provides a real-time, comprehensive assessment of nervous system function and allows for safer, more aggressive management of skull base tumors via the endonasal route.
RESUMEN
Objectives The study aims to determine factors that augment endonasal exposure of the cervical spine. Setting We used fluoroscopy and endoscopy to study endonasal visualization of the upper cervical spine. Participants Ten cadavers with normal anatomy were studied. Main Outcome Measures Endoscopic visualization was simulated with projected lines from an endoscope to the cervical spine in multiple positions. Results Neck position alone did not affect the extent of endonasal exposure of the upper cervical spine, although there was a trend correlating the extended neck position with more caudal exposure. The greatest impact was with concurrent use of a 30-degree endoscope and neck extension, and more caudal access was achieved by tilting the endoscope against the piriform aperture, using the posterior tip of the hard palate as the fulcrum. Conclusions Concurrent use of a 30-degree endoscope and neck extension increased the degree of exposure down the cervical spine. Maximum endonasal exposure of the upper cervical spine was obtained by maneuvering instruments at the fulcrum of the posterior hard palate and the nares, rather than changing the position of the neck alone. These results complement radiographic morphometric data in Part 1 of this study for preoperative assessment and surgical planning.
RESUMEN
Recent small, retrospective series suggest bevacizumab may be a therapeutic option for recurrent pediatric low-grade glioma (LGG). Assessment of therapeutic responses is complicated by the unpredictable natural history of these tumors. Because diffusion-weighted imaging quantifies microscopic water motion affected by cellular density and histologic features, we hypothesized that it may be helpful in monitoring therapeutic response of LGG to bevacizumab. We retrospectively reviewed eight consecutive patients, median age 4.8 (range 2.3-12.3) years at initiation of bevacizumab therapy for recurrent or refractory LGG. Patients received 10 mg/kg/dose every 2 weeks (median 16 doses/therapy course). Mean apparent diffusion coefficient (ADC) was measured and analyzed in respect to tumor volume. Following the first treatment course, seven of eight patients had reduced tumor volume (≥25 %) and ADC. The median decrease in tumor volume was 47% (range -6 to 78 %) and the median decrease in ADC was 14 % (range -5 to 30 %). The ADC was significantly decreased during therapy, whereas the decrease in volume was seen only after therapy completion. There was a positive correlation between percent change in tumor volume and ADC (p < 0.05). We report a decrease in tumor ADC during initial bevacizumab therapy that is accompanied by a decrease in volume following therapy. Imaging changes in microscopic water motion associated with histology may be useful in monitoring the therapeutic response of LGG to bevacizumab.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Glioma/tratamiento farmacológico , Glioma/patología , Adolescente , Encéfalo/efectos de los fármacos , Encéfalo/patología , Niño , Preescolar , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Estudios RetrospectivosRESUMEN
Citrate, a tricarboxylic acid cycle intermediate, is present in high concentrations in pediatric diffuse intrinsic pontine gliomas (DIPG). Since citrate increases during hypoxia in animal studies, we hypothesized that it accumulates in DIPG when hypoperfused. Relative tumor blood volumes (rTBV) were determined, using dynamic susceptibility contrast-enhanced magnetic resonance imaging, in twelve children [median age 8.2 (range 3.2-14.5) years] with DIPG and compared to citrate concentrations measured with in vivo proton magnetic resonance spectroscopy ((1)H MRS). Tissue perfusion and metabolite concentration were assessed at initial presentation and over the clinical course, yielding 36 and 46 perfusion and MR spectroscopy datasets, respectively. At presentation, DIPG blood volume was 60 ± 27 % of that measured for normal cerebellum. Citrate, which is not detectable in normal brain tissue, was present in DIPG at concentrations of 3.81 ± 1.44 mmol/kg tissue. Over the course of the disease and treatment, rTBV increased and citrate decreased (both p < 0.05) with an inverse correlation (p = 0.028). Citrate accumulation is associated with tissue hypoperfusion in DIPG.