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1.
Brain Nerve ; 72(10): 1105-1111, 2020 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-33051400

RESUMO

Meningioma and glioma represent two common primary intracranial tumors. However, the coexistence of these two lesions in the same patient at the same location is rare. Here, we present a case of a fibroblastic meningioma with a secondary glioblastoma occurring at the same location. A 67-year-old woman underwent surgery for a left frontal parasagittal meningioma, and the tumor was subtotally removed. Two years and 11 months after the surgery, the patient had a tumor at the same location with invasion into the adjacent brain, suggesting recurrent meningioma with malignant transformation. The resected tumor was confirmed histopathologically as a glioblastoma. Genetic analysis revealed that the isocitrate dehydrogenase 1 and 2 genes were wild type, and the TERT promoter mutation was detected. The gene analysis suggests that the tumor was a de novo glioblastoma, not a secondary glioblastoma from a lower-grade glioma. (Received April 9, 2020; Accepted May 27, 2020; Published October 1, 2020).


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Meníngeas , Meningioma , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Recidiva Local de Neoplasia/cirurgia
3.
PLoS One ; 15(10): e0232500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052913

RESUMO

BACKGROUND AND PURPOSE: Genetic classifications are crucial for understanding the heterogeneity of glioblastoma. Recently, perfusion MRI techniques have demonstrated associations molecular alterations. In this work, we investigated whether perfusion markers within infiltrated peripheral edema were associated with proneural, mesenchymal, classical and neural subtypes. MATERIALS AND METHODS: ONCOhabitats open web services were used to obtain the cerebral blood volume at the infiltrated peripheral edema for MRI studies of 50 glioblastoma patients from The Cancer Imaging Archive: TCGA-GBM. ANOVA and Kruskal-Wallis tests were carried out in order to assess the association between vascular features and the Verhaak subtypes. For assessing specific differences, Mann-Whitney U-test was conducted. Finally, the association of overall survival with molecular and vascular features was assessed using univariate and multivariate Cox models. RESULTS: ANOVA and Kruskal-Wallis tests for the maximum cerebral blood volume at the infiltrated peripheral edema between the four subclasses yielded false discovery rate corrected p-values of <0.001 and 0.02, respectively. This vascular feature was significantly higher (p = 0.0043) in proneural patients compared to the rest of the subtypes while conducting Mann-Whitney U-test. The multivariate Cox model pointed to redundant information provided by vascular features at the peripheral edema and proneural subtype when analyzing overall survival. CONCLUSIONS: Higher relative cerebral blood volume at infiltrated peripheral edema is associated with proneural glioblastoma subtype suggesting underlying vascular behavior related to molecular composition in that area.


Assuntos
Edema Encefálico/fisiopatologia , Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Volume Sanguíneo Cerebral , Feminino , Glioblastoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
4.
No Shinkei Geka ; 48(10): 921-926, 2020 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-33071228

RESUMO

We report a case of glioblastoma due to putaminal hemorrhage. Notably, the glioblastoma was located at some distance from the hematoma. A 42-year-old right-handed man presented with a sudden-onset headache, motor aphasia, and right hemiplegia. CT showed left putaminal hemorrhage and a mass lesion with a slightly high density in the midbrain away from the hematoma. Conservative treatment was initiated for the patient. Initially, we suspected a benign tumor-like cavernous malformation based on the CT findings. However, MRI showed ring enhancement of the mass lesion on contrast-enhanced MRI and hyperintensity on arterial spin labeling(ASL). A part of the wall of the putaminal hemorrhage also exhibited hyperintensity on ASL. Since we suspected a malignant brainstem tumor and a secondary intracerebral hemorrhage caused by this tumor, we performed a stereotactic brain biopsy. Histological examination revealed that the tumor was a wild-type IDH-1 glioblastoma. In the acute phase, the intracerebral hemorrhage presented as a hyperintensity on T1-weighted imaging. Therefore, it was difficult to distinguish hemorrhagic glioblastoma from an intracerebral hemorrhage. Even if an intracerebral hemorrhage is observed at common sites, it is important to consider the possibility of a malignant brain tumor and complete a prompt examination. In addition, ASL imaging may be useful in detecting hemorrhagic malignant brain tumors.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Hemorragia Putaminal , Adulto , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/complicações , Glioblastoma/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Hemorragia Putaminal/complicações , Hemorragia Putaminal/diagnóstico por imagem , Tomografia Computadorizada por Raios X
5.
Anticancer Res ; 40(11): 5989-5994, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109536

RESUMO

Glioblastoma (GB) is a highly aggressive and infiltrative brain tumor characterized by poor outcomes and a high rate of recurrence despite maximal safe resection, chemotherapy, and radiation. Superparamagnetic iron oxide nanoparticles (SPIONs) are a novel tool that can be used for many applications including magnetic targeting, drug delivery, gene delivery, hyperthermia treatment, cell tracking, or multiple simultaneous functions. SPIONs are studied as a magnetic resonance imaging tumor contrast agent by targeting tumor cell proteins or tumor vasculature. Drug delivery to GB tumor has been targeted with SPIONs in murine models. In addition to targeting tumor cells for imaging or drug-delivery, SPION has also been shown to be effective at targeting for hyperthermia. Along with animal models, human trials have been conducted for a number of different modes of SPION utilization, with important findings and lessons for further preclinical and clinical experiments. SPIONs are opening up several new avenues for monitoring and treatment of GB tumors; here, we review the current research and a variety of possible clinical applications.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Nanopartículas de Magnetita/uso terapêutico , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Ensaios Clínicos como Assunto , Meios de Contraste/química , Sistemas de Liberação de Medicamentos , Glioblastoma/diagnóstico por imagem , Humanos
6.
Cancer Imaging ; 20(1): 55, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758279

RESUMO

BACKGROUND: This study aims to identify robust radiomic features for Magnetic Resonance Imaging (MRI), assess feature selection and machine learning methods for overall survival classification of Glioblastoma multiforme patients, and to robustify models trained on single-center data when applied to multi-center data. METHODS: Tumor regions were automatically segmented on MRI data, and 8327 radiomic features extracted from these regions. Single-center data was perturbed to assess radiomic feature robustness, with over 16 million tests of typical perturbations. Robust features were selected based on the Intraclass Correlation Coefficient to measure agreement across perturbations. Feature selectors and machine learning methods were compared to classify overall survival. Models trained on single-center data (63 patients) were tested on multi-center data (76 patients). Priors using feature robustness and clinical knowledge were evaluated. RESULTS: We observed a very large performance drop when applying models trained on single-center on unseen multi-center data, e.g. a decrease of the area under the receiver operating curve (AUC) of 0.56 for the overall survival classification boundary at 1 year. By using robust features alongside priors for two overall survival classes, the AUC drop could be reduced by 21.2%. In contrast, sensitivity was 12.19% lower when applying a prior. CONCLUSIONS: Our experiments show that it is possible to attain improved levels of robustness and accuracy when models need to be applied to unseen multi-center data. The performance on multi-center data of models trained on single-center data can be increased by using robust features and introducing prior knowledge. For successful model robustification, tailoring perturbations for robustness testing to the target dataset is key.


Assuntos
Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Análise de Sobrevida
7.
PLoS One ; 15(7): e0236423, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735611

RESUMO

BACKGROUND: Use of functional MRI (fMRI) in pre-surgical planning is a non-invasive method for pre-operative functional mapping for patients with brain tumors, especially tumors located near eloquent cortex. Currently, this practice predominantly involves task-based fMRI (T-fMRI). Resting state fMRI (RS-fMRI) offers an alternative with several methodological advantages. Here, we compare group-level analyses of RS-fMRI vs. T-fMRI as methods for language localization. PURPOSE: To contrast RS-fMRI vs. T-fMRI as techniques for localization of language function. METHODS: We analyzed data obtained in 35 patients who had both T-fMRI and RS-fMRI scans during the course of pre-surgical evaluation. The RS-fMRI data were analyzed using a previously trained resting-state network classifier. The T-fMRI data were analyzed using conventional techniques. Group-level results obtained by both methods were evaluated in terms of two outcome measures: (1) inter-subject variability of response magnitude and (2) sensitivity/specificity analysis of response topography, taking as ground truth previously reported maps of the language system based on intraoperative cortical mapping as well as meta-analytic maps of language task fMRI responses. RESULTS: Both fMRI methods localized major components of the language system (areas of Broca and Wernicke) although not with equal inter-subject consistency. Word-stem completion T-fMRI strongly activated Broca's area but also several task-general areas not specific to language. RS-fMRI provided a more specific representation of the language system. CONCLUSION: We demonstrate several advantages of classifier-based mapping of language representation in the brain. Language T-fMRI activated task-general (i.e., not language-specific) functional systems in addition to areas of Broca and Wernicke. In contrast, classifier-based analysis of RS-fMRI data generated maps confined to language-specific regions of the brain.


Assuntos
Encéfalo/diagnóstico por imagem , Área de Broca/patologia , Glioblastoma/diagnóstico , Imagem por Ressonância Magnética , Adulto , Idoso , Atenção/fisiologia , Mapeamento Encefálico/métodos , Área de Broca/diagnóstico por imagem , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Lateralidade Funcional/fisiologia , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Descanso/fisiologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Adulto Jovem
8.
Artigo em Russo | MEDLINE | ID: mdl-32759928

RESUMO

Combination of meningioma and glioblastoma within the same anatomical region is casuistry. We found only 13 case reports in the available literature. Some of the authors reported induced nature of the second tumor, i.e. development under the influence of the primary neoplasm. We report a patient with glioblastoma of the right frontoparietotemporal region in 3 years after previous resection of benign right-sided meningioma of sphenoid wings. Mathematical analysis of the discovered pattern resulted conclusion about its random nature, i.e. no causal relationship between both neoplasms.


Assuntos
Glioblastoma/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Humanos , Osso Esfenoide
9.
Mol Cancer Ther ; 19(9): 1922-1929, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32606015

RESUMO

Maximal safe resection of malignant tissue is associated with improved progression-free survival and better response to radiation and chemotherapy for patients with glioblastoma (GBM). 5-Aminolevulinic acid (5-ALA) is the current FDA-approved standard for intraoperative brain tumor visualization. Unfortunately, autofluorescence in diffuse areas and high fluorescence in dense tissues significantly limit discrimination at tumor margins. This study is the first to compare 5-ALA to an investigational new drug, panitumumab-IRDye800CW, in the same animal model. A patient-derived GBM xenograft model was established in 16 nude mice, which later received injections of 5-ALA, panitumumab-IRDye800CW, IRDye800CW, 5-ALA and IRDye800CW, or 5-ALA and panitumumab-IRDye800CW. Brains were prepared for multi-instrument fluorescence imaging, IHC, and quantitative analysis of tumor-to-background ratio (TBR) and tumor margin accuracy. Statistical analysis was compared with Wilcoxon rank-sum or paired t test. Panitumumab-IRDye800CW had a 30% higher comprehensive TBR compared with 5-ALA (P = 0.0079). SDs for core and margin regions of interest in 5-ALA-treated tissues were significantly higher than those found in panitumumab-IRDye800CW-treated tissues (P = 0.0240 and P = 0.0284, respectively). Panitumumab-IRDye800CW specificities for tumor core and margin were more than 10% higher than those of 5-ALA. Higher AUC for panitumumab-IRDye800CW indicated strong capability to discriminate between normal and malignant brain tissue when compared with 5-ALA. This work demonstrates that panitumumab-IRDye800CW shows potential as a targeting agent for fluorescence intraoperative detection of GBM. Improved margin definition and surgical resection using panitumumab-IRDye800 has the potential to improve surgical outcomes and survival in patients with GBM compared with 5-ALA.


Assuntos
Ácido Aminolevulínico/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Imagem Óptica/métodos , Panitumumabe/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Ácido Aminolevulínico/farmacologia , Animais , Antineoplásicos Imunológicos/farmacologia , Feminino , Humanos , Camundongos , Camundongos Nus , Panitumumabe/farmacologia , Fármacos Fotossensibilizantes/farmacologia
10.
Int J Nanomedicine ; 15: 4677-4689, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669844

RESUMO

Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have displayed multifunctional applications in cancer theranostics following systemic delivery. In an effort to increase the therapeutic potential of local therapies (including focal hyperthermia), nanoparticles can also be administered intratumorally. Therefore, the development of a reliable pharmacokinetic model for the prediction of nanoparticle distribution for both clinically relevant routes of delivery is of high importance. Materials and Methods: The biodistribution of SPIONs (of two different sizes - 130 nm and 60 nm) radiolabeled with zirconium-89 or technetium-99m following intratumoral or intravenous injection was investigated in C57/Bl6 mice bearing subcutaneous GL261 glioblastomas. Based on PET/CT biodistribution data, a novel pharmacokinetic model was established for a better understanding of the pharmacokinetics of the SPIONs after both administration routes. Results: The PET image analysis of the nanoparticles (confirmed by histology) demonstrated the presence of radiolabeled nanoparticles within the glioma site (with low amounts in the liver and spleen) at all investigated time points following intratumoral injection. The mathematical model confirmed the dynamic nanoparticle redistribution in the organism over a period of 72 h with an equilibrium reached after 100 h. Intravenous injection of nanoparticles demonstrated a different distribution pattern with a rapid particle retention in all organs (particularly in liver and spleen) and a subsequent slow release rate. Conclusion: The mathematical model demonstrated good agreement with experimental data derived from tumor mouse models suggesting the value of this tool to predict the real-time pharmacokinetic features of SPIONs in vivo. In the future, it is planned to adapt our model to other nanoparticle formulations to more precisely describe their biodistribution in in vivo model systems.


Assuntos
Compostos Férricos/administração & dosagem , Compostos Férricos/farmacocinética , Glioblastoma/diagnóstico por imagem , Nanopartículas de Magnetita/administração & dosagem , Animais , Feminino , Glioblastoma/patologia , Injeções , Injeções Intravenosas , Nanopartículas de Magnetita/química , Camundongos Endogâmicos C57BL , Modelos Biológicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Radioisótopos/farmacocinética , Tecnécio/farmacocinética , Nanomedicina Teranóstica/métodos , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto , Zircônio/farmacocinética
11.
Nat Commun ; 11(1): 3669, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699356

RESUMO

Recent characterization of spatiotemporal genomic architecture of IDH-wild-type multifocal glioblastomas (M-GBMs) suggests a clinically unobserved common-ancestor (CA) with a less aggressive phenotype, generating highly genetically divergent malignant gliomas/GBMs in distant brain regions. Using serial MRI/3D-reconstruction, whole-genome sequencing and spectral karyotyping-based single-cell phylogenetic tree building, we show two distinct types of tumor evolution in p53-mutant driven mouse models. Malignant gliomas/GBMs grow as a single mass (Type 1) and multifocal masses (Type 2), respectively, despite both exhibiting loss of Pten/chromosome 19 (chr19) and PI3K/Akt activation with sub-tetraploid/4N genomes. Analysis of early biopsied and multi-segment tumor tissues reveals no evidence of less proliferative diploid/2N lesions in Type 1 tumors. Strikingly, CA-derived relatively quiescent tumor precursors with ancestral diploid/2N genomes and normal Pten/chr19 are observed in the subventricular zone (SVZ), but are distantly segregated from multi focal Type 2 tumors. Importantly, PI3K/Akt inhibition by Rictor/mTORC2 deletion blocks distant dispersal, restricting glioma growth in the SVZ.


Assuntos
Neoplasias Encefálicas/genética , Carcinogênese/genética , Evolução Clonal , Evolução Molecular , Glioblastoma/genética , Animais , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Variações do Número de Cópias de DNA , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Isocitrato Desidrogenase/genética , Cariotipagem , Imagem por Ressonância Magnética , Alvo Mecanístico do Complexo 2 de Rapamicina/genética , Camundongos , Camundongos Transgênicos , Mutação , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Companheira de mTOR Insensível à Rapamicina/genética , Transdução de Sinais/genética , Análise de Célula Única , Sequenciamento Completo do Genoma
12.
PLoS One ; 15(6): e0234772, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555746

RESUMO

Glioblastoma is the most aggressive primary brain tumor leading to death in most of patients. It comprises almost 50-55% of all gliomas with an incidence rate of 2-3 per 100,000. Despite its rarity, overall mortality of glioblastoma is comparable to the most frequent tumors. The current standard treatment combines surgical resection, radiotherapy and chemotherapy with temozolomide. In spite of this aggressive multimodality protocol, prognosis of glioblastoma is poor and the median survival remains about 12-14.5 months. In this regard, new therapeutic approaches should be developed to improve the life quality and survival time of the patient after the initial diagnosis. Before switching to clinical trials in humans, all innovative therapeutic methods must be studied first on a relevant animal model in preclinical settings. In this regard, we validated the feasibility of intratumoral delivery of a holmium (Ho) microparticle suspension to an induced U87 glioblastoma model. Among the different radioactive beta emitters, 166Ho emits high-energy ß(-) radiation and low-energy γ radiation. ß(-) radiation is an effective means for tumor destruction and γ rays are well suited for imaging (SPECT) and consequent dosimetry. In addition, the paramagnetic Ho nucleus is a good asset to perform MRI imaging. In this study, five minipigs, implanted with our glioblastoma model were used to test the injectability of 165Ho (stable) using a bespoke injector and needle. The suspension was produced in the form of Ho microparticles and injected inside the tumor by a technique known as microbrachytherapy using a stereotactic system. At the end of this trial, it was found that the 165Ho suspension can be injected successfully inside the tumor with absence or minimal traces of Ho reflux after the injections. This injection technique and the use of the 165Ho suspension needs to be further assessed with radioactive 166Ho in future studies.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Hólmio/química , Compostos Radiofarmacêuticos/administração & dosagem , Siloxanas/química , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Masculino , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Suínos , Porco Miniatura , Tomografia Computadorizada de Emissão de Fóton Único , Transplante Heterólogo
14.
Clin Nucl Med ; 45(8): 621-622, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32520501

RESUMO

After standard treatment of glioblastoma, pseudoprogression versus true progression is a clinical challenge. Indeed, to differentiate these 2 on contrast MRI (cMRI) is problematic. In recent time, Ga-prostate-specific membrane antigen-11 (Ga-PSMA) PET/CT has been suggested to have high accuracy in glioblastoma recurrence. We present a case of a 40-year-old man with right frontotemporal glioblastoma underwent surgery and radiotherapy. One month posttreatment cMRI showed a new enhancing lesion in the right hippocampal region, which was also positive on Ga-PSMA-11 PET/CT. On follow-up with conservative management, both cMRI and Ga-PSMA-11 PET/CT showed regression in new lesion, hence suggest pseudoprogression.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Humanos , Masculino , Glicoproteínas de Membrana , Recidiva Local de Neoplasia/patologia , Compostos Organometálicos , Compostos Radiofarmacêuticos
15.
PLoS One ; 15(6): e0234182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492056

RESUMO

The development of noninvasive approaches for brain tumor diagnosis and monitoring continues to be a major medical challenge. Although blood-based liquid biopsy has received considerable attention in various cancers, limited progress has been made for brain tumors, at least partly due to the hindrance of tumor biomarker release into the peripheral circulation by the blood-brain barrier. Focused ultrasound (FUS) combined with microbubbles induced BBB disruption has been established as a promising technique for noninvasive and localized brain drug delivery. Building on this established technique, we propose to develop FUS-enabled liquid biopsy technique (FUS-LBx) to enhance the release of brain tumor biomarkers (e.g., DNA, RNA, and proteins) into the circulation. The objective of this study was to demonstrate that FUS-LBx could sufficiently increase plasma levels of brain tumor biomarkers without causing hemorrhage in the brain. Mice with orthotopic implantation of enhanced green fluorescent protein (eGFP)-transfected murine glioma cells were treated using magnetic resonance (MR)-guided FUS system in the presence of systemically injected microbubbles at three peak negative pressure levels (0.59, 1.29, and 1.58 MPa). Plasma eGFP mRNA levels were quantified with the quantitative polymerase chain reaction (qPCR). Contrast-enhanced MR images were acquired before and after the FUS sonication. FUS at 0.59 MPa resulted in an increased plasma eGFP mRNA level, comparable to those at higher acoustic pressures (1.29 MPa and 1.58 MPa). Microhemorrhage density associated with FUS at 0.59 MPa was significantly lower than that at higher acoustic pressures and not significantly different from the control group. MRI analysis revealed that post-sonication intratumoral and peritumoral hyperenhancement had strong correlations with the level of FUS-induced biomarker release and the extent of hemorrhage. This study suggests that FUS-LBx could be a safe and effective brain-tumor biomarker release technique, and MRI could be used to develop image-guided FUS-LBx.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Ultrassonografia de Intervenção/métodos , Animais , Biomarcadores Tumorais/sangue , Barreira Hematoencefálica , Neoplasias Encefálicas/diagnóstico por imagem , Linhagem Celular Tumoral , Meios de Contraste , Feminino , Glioblastoma/diagnóstico por imagem , Proteínas de Fluorescência Verde/sangue , Proteínas de Fluorescência Verde/genética , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/patologia , Biópsia Líquida/métodos , Imagem por Ressonância Magnética , Camundongos , Ultrassonografia de Intervenção/efeitos adversos
16.
J Neurol Surg A Cent Eur Neurosurg ; 81(4): 348-354, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32361984

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive intracranial malignancy that confers a poor prognosis despite maximum surgical resection and chemoradiotherapy. Survival decreases further with deep-seated lesions. Laser interstitial thermal therapy (LITT) is an emerging minimally invasive technique for tumor ablation shown to reduce tumor burden effectively, particularly in deep-seated locations less amenable to gross total resection. We describe our initial technical experience of using the combination of LITT followed by surgical resection in patients with GBMs that exhibit both an easily accessible and deep-seated component. MATERIALS AND METHODS: Patients with GBM who received concurrent LITT and surgical resection at our institution were identified. Patient demographic and clinical information was procured from the University of Texas MD Anderson Cancer Center electronic medical record along with preoperative, postoperative, and 1-month follow-up magnetic resonance imaging (MRI). RESULTS: Four patients (n = 2 male, n = 2 female) with IDH-wild type GBM who received combined LITT and surgical resection were identified and analyzed retrospectively. All patients received chemoradiotherapy before presentation. All but one patient (75%) received resection before presentation. Median age was 54 years (range: 44-56 years). Median length of hospital stay was 6.5 days (range: 2-47 days). Median extent of combined ablation/resection was 90.4%. One of the four patients experienced complications in the perioperative or immediate follow-up periods. Local recurrence was observed in one patient during the follow-up period. CONCLUSION: Malignant gliomas in deep-seated locations or in close proximity to white matter structures are challenging to manage. LITT followed by surgical resection may provide an alternative for tumor debulking that minimizes potential morbidities and extent of residual tumor. Further studies comparing this approach with standard resection techniques are warranted.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Terapia a Laser/métodos , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
17.
Cancer Imaging ; 20(1): 35, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398076

RESUMO

BACKGROUND: Anti-angiogenic treatment of glioblastoma (GBM) complicates radiologic monitoring. We evaluated magnetic resonance elastography (MRE) as an imaging tool for monitoring the efficacy of anti-VEGF treatment of GBM. METHODS: Longitudinal studies were performed in an orthotopic GBM xenograft mouse model. Animals treated with B20 anti-VEGF antibody were compared to untreated controls regarding survival (n = 13), classical MRI-contrasts and biomechanics as quantified via MRE (n = 15). Imaging was performed on a 7 T small animal horizontal bore MRI scanner. MRI and MRE parameters were compared to histopathology. RESULTS: Anti-VEGF-treated animals survived longer than untreated controls (p = 0.0011) with progressively increased tumor volume in controls (p = 0.0001). MRE parameters viscoelasticity |G*| and phase angle Y significantly decreased in controls (p = 0.02 for |G*| and p = 0.0071 for Y). This indicates that untreated tumors became softer and more elastic than viscous with progression. Tumor volume in treated animals increased more slowly than in controls, indicating efficacy of the therapy, reaching significance only at the last time point (p = 0.02). Viscoelasticity and phase angle Y tended to decrease throughout therapy, similar as for control animals. However, in treated animals, the decrease in phase angle Y was significantly attenuated and reached statistical significance at the last time point (p = 0.04). Histopathologically, control tumors were larger and more heterogeneous than treated tumors. Vasculature was normalized in treated tumors compared with controls, which showed abnormal vasculature and necrosis. In treated tumors, a higher amount of myelin was observed within the tumor area (p = 0.03), likely due to increased tumor invasion. Stiffness of the contralateral hemisphere was influenced by tumor mass effect and edema. CONCLUSIONS: Anti-angiogenic GBM treatment prolonged animal survival, slowed tumor growth and softening, but did not prevent progression. MRE detected treatment effects on tumor stiffness; the decrease of viscoelasticity and phase angle in GBM was attenuated in treated animals, which might be explained by normalized vasculature and greater myelin preservation within treated tumors. Thus, further investigation of MRE is warranted to understand the potential for MRE in monitoring treatment in GBM patients by complementing existing MRI techniques.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Neoplasias Encefálicas/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Glioblastoma/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Inibidores da Angiogênese/uso terapêutico , Animais , Anticorpos/efeitos adversos , Anticorpos/imunologia , Anticorpos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Feminino , Glioblastoma/tratamento farmacológico , Camundongos , Camundongos Nus , Fator A de Crescimento do Endotélio Vascular/imunologia
18.
Int J Nanomedicine ; 15: 3057-3070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431501

RESUMO

Background: Position of gadolinium atom(s) plays a key role in contrast enhancement of gadolinium-based contrast agents. To gain a better understanding of effects of distance of gadolinium in relation to the nanoconjugate platform, we designed and synthesized single- and multi-arm ("star") gadolinium conjugates equipped with antibody and peptides for targeting. The contrast agents were studied for their tumor imaging performance in a glioma mouse model. Materials and Methods: Antibody- and peptide-targeted nano contrast agents (NCAs) were synthesized using polymalic acid platforms of different sizes. Gadolinium-DOTA and intermediates were attached as amides and targeting agents such as antibodies and peptides as thioethers. For in vivo experiments, we used human U87MG xenografts as glioma models. Magnetic resonance imaging (MRI) was performed on a Bruker BioSpec 94/20USR 9.4 T small-animal scanner. Delivery of contrast agents across the blood-brain barrier was studied by fluorescent microscopy. Results: All contrast agents accumulated into tumor and showed composition-dependent imaging performance. Peptide-targeted mini-NCAs had hydrodynamic diameters in the range 5.2-9.4 nm and antibody-targeted NCAs had diameters in the range 15.8-20.5 nm. Zeta potentials were in the range of -5.4--8.2 mV and -4.6--8.8 mV, respectively. NCAs showed superior relaxivities compared to MultiHance at 9.4 T. The signal enhancement indicated maximum accumulation in tumor 30-60 minutes after intravenous injection of the mouse tail vein. Only targeted NCAs were retained in tumor for up to 3 hours and displayed contrast enhancement. Conclusion: The novel targeted NCAs with star-PEG features displayed improved relaxivity and greater contrast compared with commercial MultiHance contrast agent. The enhancement by mini-NCAs showed clearance of tumor contrast after 3 hours providing a suitable time window for tumor diagnosis in clinics. The technology provides a great tool with the promise of differential MRI diagnosis of brain tumors.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Glioblastoma/diagnóstico por imagem , Compostos Heterocíclicos/administração & dosagem , Imagem por Ressonância Magnética/métodos , Compostos Organometálicos/administração & dosagem , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacocinética , Modelos Animais de Doenças , Feminino , Humanos , Meglumina/administração & dosagem , Meglumina/análogos & derivados , Meglumina/farmacocinética , Camundongos Nus , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Compostos Organometálicos/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
BMC Neurol ; 20(1): 178, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393192

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumors. Intracranial GBM metastases to the spine are rarely detected clinically. Secondary gliosarcomas after treatment of primary GBM are rarely described. CASE PRESENTATION: Herein, we report the case of a 53-year-old woman who presented to our emergency room with progressive headache and weakness on the left side. Plain computed tomography and contrast magnetic resonance imaging of the brain revealed an approximately 6.8 cm × 4.5 cm right temporoparietooccipital intraaxial cystic tumor with surrounding diffuse perifocal edema that caused midline shift toward the left. Emergency craniotomy was performed to remove the tumor, and pathological examination revealed GBM. The patient received proton beam therapy, Gliadel implantation, and oral temozolomide chemotherapy as well as targeted therapy with bevacizumab. Approximately 15 months after diagnosis, she underwent surgical resection of the right temporal recurrent tumor and was newly diagnosed as having a metastatic spinal tumor. Pathologically, the right temporal and metastatic spinal tumors were gliosarcoma and GBM, respectively. CONCLUSIONS: Concurrent spinal metastasis and gliosarcomatous transformation, which are two types of GBM complications, are rare. To our knowledge, this is the first report of a case of recurrent GBM with gliosarcoma after proton bean therapy.


Assuntos
Neoplasias Encefálicas/patologia , Encéfalo/patologia , Glioblastoma/secundário , Gliossarcoma/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Coluna Vertebral/secundário , Antineoplásicos Alquilantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Craniotomia , Evolução Fatal , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/terapia , Terapia com Prótons , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Temozolomida/uso terapêutico , Tomografia Computadorizada por Raios X
20.
Korean J Radiol ; 21(6): 707-716, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32410409

RESUMO

OBJECTIVE: To evaluate pharmacokinetic variables from contrast-enhancing lesions (CELs) and non-enhancing T2 high signal intensity lesions (NE-T2HSILs) on dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in glioblastoma (GBM) patients. MATERIALS AND METHODS: Sixty-four GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. We analyzed the pharmacokinetic variables of the volume transfer constant (Ktrans) and volume fraction of extravascular extracellular space within the CEL and NE-T2HSIL of the entire tumor. Univariate and multivariate Cox regression analyses were performed using preoperative clinical characteristics, pharmacokinetic variables of DCE MR imaging, and postoperative molecular biomarkers to predict PFS. RESULTS: The increased mean Ktrans of the CEL, increased 95th percentile Ktrans of the CELs, and absence of methylated O6-methylguanine-DNA methyltransferase promoter were relevant adverse variables for PFS in the univariate analysis (p = 0.041, p = 0.032, and p = 0.083, respectively). The Kaplan-Meier survival curves demonstrated that PFS was significantly shorter in patients with a mean Ktrans of the CEL > 0.068 and 95th percentile Ktrans of the CEL>0.223 (log-rank p = 0.038 and p = 0.041, respectively). However, only mean Ktrans of the CEL was significantly associated with PFS (p = 0.024; hazard ratio, 553.08; 95% confidence interval, 2.27-134756.74) in the multivariate Cox proportional hazard analysis. None of the pharmacokinetic variables from NE-T2HSILs were significantly related to PFS. CONCLUSION: Among the pharmacokinetic variables extracted from CELs and NE-T2HSILs on preoperative DCE MR imaging, the mean Ktrans of CELs exhibits potential as a useful imaging predictor of PFS in GBM patients.


Assuntos
Neoplasias Encefálicas/diagnóstico , Meios de Contraste/química , Glioblastoma/diagnóstico , Imagem por Ressonância Magnética , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Meios de Contraste/farmacocinética , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/mortalidade , Humanos , Processamento de Imagem Assistida por Computador , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
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