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Sample records for brain tumor tissue

  1. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  2. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    PubMed Central

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-01-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue. PMID:27456312

  3. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  4. Non-diffeomorphic registration of brain tumor images by simulating tissue loss and tumor growth.

    PubMed

    Zacharaki, Evangelia I; Hogea, Cosmina S; Shen, Dinggang; Biros, George; Davatzikos, Christos

    2009-07-01

    Although a variety of diffeomorphic deformable registration methods exist in the literature, application of these methods in the presence of space-occupying lesions is not straightforward. The motivation of this work is spatial normalization of MR images from patients with brain tumors in a common stereotaxic space, aiming to pool data from different patients into a common space in order to perform group analyses. Additionally, transfer of structural and functional information from neuroanatomical brain atlases into the individual patient's space can be achieved via the inverse mapping, for the purpose of segmenting brains and facilitating surgical or radiotherapy treatment planning. A method that estimates the brain tissue loss and replacement by tumor is applied for achieving equivalent image content between an atlas and a patient's scan, based on a biomechanical model of tumor growth. Automated estimation of the parameters modeling brain tissue loss and displacement is performed via optimization of an objective function reflecting feature-based similarity and elastic stretching energy, which is optimized in parallel via APPSPACK (Asynchronous Parallel Pattern Search). The results of the method, applied to 21 brain tumor patients, indicate that the registration accuracy is relatively high in areas around the tumor, as well as in the healthy portion of the brain. Also, the calculated deformation in the vicinity of the tumor is shown to correlate highly with expert-defined visual scores indicating the tumor mass effect, thereby potentially leading to an objective approach to quantification of mass effect, which is commonly used in diagnosis. PMID:19408350

  5. Brain tumor (image)

    MedlinePlus

    Brain tumors are classified depending on the exact site of the tumor, the type of tissue involved, benign ... tendencies of the tumor, and other factors. Primary brain tumors can arise from the brain cells, the meninges ( ...

  6. Differentiation of healthy brain tissue and tumors using surface-enhanced Raman scattering.

    PubMed

    Aydin, Omer; Altaş, Murat; Kahraman, Mehmet; Bayrak, Omer Faruk; Culha, Mustafa

    2009-10-01

    Surface-enhanced Raman scattering (SERS) is a powerful technique for characterization of biological samples. SERS spectra from healthy brain tissue and tumors are obtained by sudden freezing of tissue in liquid nitrogen and crashing and mixing it with a concentrated silver colloidal suspension. The acquired spectra from tissues show significant spectral differences that can be used to identify whether it is from a healthy region or tumor. The most significant change on SERS spectra from the healthy/peripheral brain tissue to tumor is the increase of the ratio of the peaks at around 723 to 655 cm(-1). In addition, the spectral changes indicate that the protein content in tumors increases compared to the peripheral/healthy tissue as observed with tumor invasion. The preliminary results show that SERS spectra can be used for a quick diagnosis due to the simplicity of the sample preparation and the speed of the spectral acquisition. PMID:19843358

  7. Brain Tumors

    MedlinePlus

    ... brain. Brain tumors can be benign, with no cancer cells, or malignant, with cancer cells that grow quickly. Some are primary brain ... targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. Many people get ...

  8. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  9. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    PubMed

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining. PMID:26830089

  10. Magnetic Resonance Microscopy at 14 Tesla and Correlative Histopathology of Human Brain Tumor Tissue

    PubMed Central

    Gonzalez-Segura, Ana; Morales, Jose Manuel; Gonzalez-Darder, Jose Manuel; Cardona-Marsal, Ramon; Lopez-Gines, Concepcion; Cerda-Nicolas, Miguel; Monleon, Daniel

    2011-01-01

    Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 µm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples. PMID:22110653

  11. Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

    ClinicalTrials.gov

    2016-05-17

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

  12. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    NASA Astrophysics Data System (ADS)

    Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

    2016-05-01

    The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

  13. Segmentation of tumor and edema along with healthy tissues of brain using wavelets and neural networks.

    PubMed

    Demirhan, Ayşe; Toru, Mustafa; Guler, Inan

    2015-07-01

    Robust brain magnetic resonance (MR) segmentation algorithms are critical to analyze tissues and diagnose tumor and edema in a quantitative way. In this study, we present a new tissue segmentation algorithm that segments brain MR images into tumor, edema, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). The detection of the healthy tissues is performed simultaneously with the diseased tissues because examining the change caused by the spread of tumor and edema on healthy tissues is very important for treatment planning. We used T1, T2, and FLAIR MR images of 20 subjects suffering from glial tumor. We developed an algorithm for stripping the skull before the segmentation process. The segmentation is performed using self-organizing map (SOM) that is trained with unsupervised learning algorithm and fine-tuned with learning vector quantization (LVQ). Unlike other studies, we developed an algorithm for clustering the SOM instead of using an additional network. Input feature vector is constructed with the features obtained from stationary wavelet transform (SWT) coefficients. The results showed that average dice similarity indexes are 91% for WM, 87% for GM, 96% for CSF, 61% for tumor, and 77% for edema. PMID:25265636

  14. Segmenting nonenhancing brain tumors from normal tissues in magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Fletcher-Heath, Lynn M.; Hall, Lawrence O.; Goldgof, Dmitry B.

    1998-06-01

    Tumor segmentation from magnetic resonance (MR) images aids in tumor treatment by tracking the progress of tumor growth and/or shrinkage. In this paper we present an automatic segmentation method which separates non-enhancing brain tumors from healthy tissues in MR images. The MR feature images used for the segmentation consist of three weighted images (T1, T2 and proton density) for each axial slice through the head. An initial segmentation is computed using an unsupervised clustering algorithm. Then, integrated domain knowledge and image processing techniques contribute to the final tumor segmentation. The system was trained on two patient volumes and preliminary testing has shown successful tumor segmentations on four patient volumes.

  15. Bimodal Spectroscopy of Formalin Fixed Samples to Discriminate Dysplastic and Tumor Brain Tissues

    NASA Astrophysics Data System (ADS)

    Anand, S.; Cicchi, R.; Giordano, F.; Buccoliero, A. M.; Guerrini, R.; Pavone, F. S.

    2014-12-01

    Biomedical spectroscopy has gained attention in the past few years for disease diagnosis. Fluorescence and Raman spectroscopies provide finger-print information related to biochemical and morphological alterations when tissues progress from the normal to a malignant stage. Usually, freshly excised tissue specimens are preferred for bio-spectroscopic studies. However, ethical issues, sample availability and distance between the surgery room and the laboratory provide an impelling restriction for in-vitro spectroscopic studies using freshly excised samples. After surgical resection tissues are fixed in 4% formalin for histological studies under a light microscope. The process of fixation prevents degradation of tissues. In this study, we probe the use of formalin fixed sample for differentiating normal and dysplastic brain tissues using fluorescence and Raman spectroscopies. It was found that fluorescence spectral profile changes in the wavelength range from 550-750 nm between dysplastic and tumor samples. Also, significant differences were found in the Raman spectral profiles of such samples. The results indicate a potential diagnostic application of spectroscopy in formalin fixed brain samples for differentiating dysplastic and tumor brain tissues.

  16. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  17. Terahertz spectroscopy and detection of brain tumor in rat fresh-tissue samples

    NASA Astrophysics Data System (ADS)

    Yamaguchi, S.; Fukushi, Y.; Kubota, O.; Itsuji, T.; Yamamoto, S.; Ouchi, T.

    2015-03-01

    Terahertz (THz) spectroscopy and imaging of biomedical samples is expected to be an important application of THz analysis techniques. Identification and localization of tumor tissue, imaging of biological samples, and analysis of DNA by THz spectroscopy have been reported. THz time-domain spectroscopy (TDS) is useful for obtaining the refractive index over a broad frequency range. However, THz-TDS spectra of fresh tissue samples are sensitive to procedures such as sample preparation, and a standardized measurement protocol is required. Therefore, in this work, we establish a protocol for measurements of THz spectra of fresh tissue and demonstrate reliable detection of rat brain tumor tissue. We use a reflection THz-TDS system to measure the refractive index spectra of the samples mounted on a quartz plate. The tissue samples were measured immediately after sectioning to avoid sample denaturalization during storage. Special care was taken in THz data processing to eliminate parasitic reflections and reduce noise. The error level in our refractive index measurements was as low as 0.02 in the frequency range 0.8-1.5 THz. With increasing frequency, the refractive index in the tumor and normal regions monotonically decreased, similarly to water, and it was 0.02 higher in the tumor regions. The spectral data suggest that the tumor regions have higher water content. Hematoxylin-eosin stained images showed that increased cell density was also responsible for the observed spectral features. A set of samples from 10 rats showed consistent results. Our results suggest that reliable tumor detection in fresh tissue without pretreatment is possible with THz spectroscopy measurements. THz spectroscopy has the potential to become a real-time in vivo diagnostic method.

  18. Influence of brain tumors on the MR spectra of healthy brain tissue.

    PubMed

    Busch, M; Liebenrodt, K; Gottfried, S; Weiland, E; Vollmann, W; Mateiescu, S; Winter, S; Lange, S; Sahinbas, H; Baier, J; van Leeuwen, P; Grönemeyer, D

    2011-01-01

    The neurochemical environment of nontumorous white matter tissue was investigated in 135 single voxel spectra of "healthy" white matter regions of 43 tumor patients and 129 spectra of 52 healthy subjects. Spectra were acquired with short TE and TR values. With the data of tumor patients, it was examined whether differences were caused by the tumor itself or aggressive tumor therapies as confounding factors. Comparing the spectra of both classes, an excellent differentiation was possible based on the metabolite peak of N-acetylaspartate (P ≈ 0) and myoinositol (P < 0.03). The area under curve of the receiver operating characteristic was calculated as 0.86 and 0.62, respectively. With linear discriminant analysis using combinations of integrals, a prediction was possible, whether a spectrum belonged to the patient or the healthy subject class with an overall accuracy above 80%. The confounding factors could be ruled out as source of the differences. The results show strong evidence for an influence of malignant growth on the biochemical environment of nontumorous white matter tissue. Because of the T(1) weighting, the measured differences between both classes were most likely concentration changes interfered by T(1) effects. The underlying processes will be subject of future studies. PMID:20859993

  19. Radioresistance of Brain Tumors

    PubMed Central

    Kelley, Kevin; Knisely, Jonathan; Symons, Marc; Ruggieri, Rosamaria

    2016-01-01

    Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We also evaluate existing approaches to induce radiosensitization and explore future avenues of investigation. PMID:27043632

  20. Understanding Brain Tumors

    MedlinePlus

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  1. Brain tumor - children

    MedlinePlus

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  2. Brain Tumor Diagnosis

    MedlinePlus

    ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ... Types of Brain Scans X-rays Laboratory Tests DNA Profiling Biopsy Procedure Malignant and Benign Brain Tumors Tumor ...

  3. Brain Tumors (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Brain Tumors KidsHealth > For Parents > Brain Tumors Print A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  4. Metastatic brain tumor

    MedlinePlus

    Brain tumor - metastatic (secondary); Cancer - brain tumor (metastatic) ... For many people with metastatic brain tumors, the cancer is not curable. It will eventually spread to other areas of the body. Prognosis depends on the type of tumor ...

  5. Adolescent and Pediatric Brain Tumors

    MedlinePlus

    ... abta.org Donate Now Menu Adolescent & Pediatric Brain Tumors Brain Tumors In Children Pediatric Brain Tumor Diagnosis Family ... or Complete our contact form Adolescent & Pediatric Brain Tumors Brain Tumors In Children Pediatric Brain Tumor Diagnosis Family ...

  6. Topical Application of Activity-based Probes for Visualization of Brain Tumor Tissue

    PubMed Central

    Cutter, Jennifer L.; Cohen, Nathan T.; Wang, Jing; Sloan, Andrew E.; Cohen, Alan R.; Panneerselvam, Ashok; Schluchter, Mark; Blum, Galia; Bogyo, Matthew; Basilion, James P.

    2012-01-01

    Several investigators have shown the utility of systemically delivered optical imaging probes to image tumors in small animal models of cancer. Here we demonstrate an innovative method for imaging tumors and tumor margins during surgery. Specifically, we show that optical imaging probes topically applied to tumors and surrounding normal tissue rapidly differentiate between tissues. In contrast to systemic delivery of optical imaging probes which label tumors uniformly over time, topical probe application results in rapid and robust probe activation that is detectable as early as 5 minutes following application. Importantly, labeling is primarily associated with peri-tumor spaces. This methodology provides a means for rapid visualization of tumor and potentially infiltrating tumor cells and has potential applications for directed surgical excision of tumor tissues. Furthermore, this technology could find use in surgical resections for any tumors having differential regulation of cysteine cathepsin activity. PMID:22427947

  7. Brain Tumor Symptoms

    MedlinePlus

    ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff ... Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning Donate to the ABTA Help advance the understanding ...

  8. Metastatic brain tumor

    MedlinePlus

    ... brain from an unknown location. This is called cancer of unknown primary (CUP) origin. Growing brain tumors can place pressure ... not know the original location. This is called cancer of unknown primary (CUP) origin. Metastatic brain tumors occur in about ...

  9. Childhood Brain Tumors

    MedlinePlus

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  10. Multimodal Raman-fluorescence spectroscopy of formalin fixed samples is able to discriminate brain tumors from dysplastic tissue

    NASA Astrophysics Data System (ADS)

    Anand, Suresh; Cicchi, Riccardo; Giordano, Flavio; Buccoliero, Anna Maria; Pavone, Francesco Saverio

    2014-05-01

    In the recent years, there has been a considerable surge in the application of spectroscopy for disease diagnosis. Raman and fluorescence spectra provide characteristic spectral profile related to biochemical and morphological changes when tissues progress from normal state towards malignancy. Spectroscopic techniques offer the advantage of being minimally invasive compared to traditional histopathology, real time and quantitative. In biomedical optical diagnostics, freshly excised specimens are preferred for making ex-vivo spectroscopic measurements. With regard to fresh tissues, if the lab is located far away from the clinic it could pose a problem as spectral measurements have to be performed immediately after dissection. Tissue samples are usually placed in a fixative agent such as 4% formaldehyde to preserve the samples before processing them for routine histopathological studies. Fixation prevents the tissues from decomposition by arresting autolysis. In the present study, we intend to investigate the possibility of using formalin fixed samples for discrimination of brain tumours from dysplastic tissue using Raman and fluorescence spectroscopy. Formalin fixed samples were washed with phosphate buffered saline for about 5 minutes in order to remove the effects of formalin during spectroscopic measurements. In case of fluorescence spectroscopy, changes in spectral profile have been observed in the region between 550-670 nm between dysplastic and tumor samples. For Raman measurements, we found significant differences in the spectral profiles between dysplasia and tumor. In conclusion, formalin fixed samples can be potentially used for the spectroscopic discrimination of tumor against dysplastic tissue in brain samples.

  11. Toward a real time multi-tissue Adaptive Physics-Based Non-Rigid Registration framework for brain tumor resection

    PubMed Central

    Drakopoulos, Fotis; Foteinos, Panagiotis; Liu, Yixun; Chrisochoides, Nikos P.

    2013-01-01

    This paper presents an adaptive non-rigid registration method for aligning pre-operative MRI with intra-operative MRI (iMRI) to compensate for brain deformation during brain tumor resection. This method extends a successful existing Physics-Based Non-Rigid Registration (PBNRR) technique implemented in ITKv4.5. The new method relies on a parallel adaptive heterogeneous biomechanical Finite Element (FE) model for tissue/tumor removal depicted in the iMRI. In contrast the existing PBNRR in ITK relies on homogeneous static FE model designed for brain shift only (i.e., it is not designed to handle brain tumor resection). As a result, the new method (1) accurately captures the intra-operative deformations associated with the tissue removal due to tumor resection and (2) reduces the end-to-end execution time to within the time constraints imposed by the neurosurgical procedure. The evaluation of the new method is based on 14 clinical cases with: (i) brain shift only (seven cases), (ii) partial tumor resection (two cases), and (iii) complete tumor resection (five cases). The new adaptive method can reduce the alignment error up to seven and five times compared to a rigid and ITK's PBNRR registration methods, respectively. On average, the alignment error of the new method is reduced by 9.23 and 5.63 mm compared to the alignment error from the rigid and PBNRR method implemented in ITK. Moreover, the total execution time for all the case studies is about 1 min or less in a Linux Dell workstation with 12 Intel Xeon 3.47 GHz CPU cores and 96 GB of RAM. PMID:24596553

  12. Toward a real time multi-tissue Adaptive Physics-Based Non-Rigid Registration framework for brain tumor resection.

    PubMed

    Drakopoulos, Fotis; Foteinos, Panagiotis; Liu, Yixun; Chrisochoides, Nikos P

    2014-01-01

    This paper presents an adaptive non-rigid registration method for aligning pre-operative MRI with intra-operative MRI (iMRI) to compensate for brain deformation during brain tumor resection. This method extends a successful existing Physics-Based Non-Rigid Registration (PBNRR) technique implemented in ITKv4.5. The new method relies on a parallel adaptive heterogeneous biomechanical Finite Element (FE) model for tissue/tumor removal depicted in the iMRI. In contrast the existing PBNRR in ITK relies on homogeneous static FE model designed for brain shift only (i.e., it is not designed to handle brain tumor resection). As a result, the new method (1) accurately captures the intra-operative deformations associated with the tissue removal due to tumor resection and (2) reduces the end-to-end execution time to within the time constraints imposed by the neurosurgical procedure. The evaluation of the new method is based on 14 clinical cases with: (i) brain shift only (seven cases), (ii) partial tumor resection (two cases), and (iii) complete tumor resection (five cases). The new adaptive method can reduce the alignment error up to seven and five times compared to a rigid and ITK's PBNRR registration methods, respectively. On average, the alignment error of the new method is reduced by 9.23 and 5.63 mm compared to the alignment error from the rigid and PBNRR method implemented in ITK. Moreover, the total execution time for all the case studies is about 1 min or less in a Linux Dell workstation with 12 Intel Xeon 3.47 GHz CPU cores and 96 GB of RAM. PMID:24596553

  13. A robust framework for soft tissue simulations with application to modeling brain tumor mass effect in 3D MR images.

    PubMed

    Hogea, Cosmina; Biros, George; Abraham, Feby; Davatzikos, Christos

    2007-12-01

    We present a framework for black-box and flexible simulation of soft tissue deformation for medical imaging and surgical planning applications. Our main motivation in the present work is to develop robust algorithms that allow batch processing for registration of brains with tumors to statistical atlases of normal brains and construction of brain tumor atlases. We describe a fully Eulerian formulation able to handle large deformations effortlessly, with a level-set-based approach for evolving fronts. We use a regular grid-fictitious domain method approach, in which we approximate coefficient discontinuities, distributed forces and boundary conditions. This approach circumvents the need for unstructured mesh generation, which is often a bottleneck in the modeling and simulation pipeline. Our framework employs penalty approaches to impose boundary conditions and uses a matrix-free implementation coupled with a multigrid-accelerated Krylov solver. The overall scheme results in a scalable method with minimal storage requirements and optimal algorithmic complexity. We illustrate the potential of our framework to simulate realistic brain tumor mass effects at reduced computational cost, for aiding the registration process towards the construction of brain tumor atlases. PMID:18029982

  14. A robust framework for soft tissue simulations with application to modeling brain tumor mass effect in 3D MR images

    NASA Astrophysics Data System (ADS)

    Hogea, Cosmina; Biros, George; Abraham, Feby; Davatzikos, Christos

    2007-12-01

    We present a framework for black-box and flexible simulation of soft tissue deformation for medical imaging and surgical planning applications. Our main motivation in the present work is to develop robust algorithms that allow batch processing for registration of brains with tumors to statistical atlases of normal brains and construction of brain tumor atlases. We describe a fully Eulerian formulation able to handle large deformations effortlessly, with a level-set-based approach for evolving fronts. We use a regular grid—fictitious domain method approach, in which we approximate coefficient discontinuities, distributed forces and boundary conditions. This approach circumvents the need for unstructured mesh generation, which is often a bottleneck in the modeling and simulation pipeline. Our framework employs penalty approaches to impose boundary conditions and uses a matrix-free implementation coupled with a multigrid-accelerated Krylov solver. The overall scheme results in a scalable method with minimal storage requirements and optimal algorithmic complexity. We illustrate the potential of our framework to simulate realistic brain tumor mass effects at reduced computational cost, for aiding the registration process towards the construction of brain tumor atlases.

  15. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... to make progress in “immunogenomics” Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  16. Children's Brain Tumor Foundation

    MedlinePlus

    ... CBTF Justin's Hope Fund Grant Recipients Grants Children’s Brain Tumor Foundation, A non-profit organization, was founded ... and the long term outlook for children with brain and spinal cord tumors through research, support, education, ...

  17. American Brain Tumor Association

    MedlinePlus

    ... 800-886-ABTA (2282) or Complete our contact form The American Brain Tumor Association was the first and is the only national organization committed to funding brain tumor research and providing ...

  18. Brain Tumor Statistics

    MedlinePlus

    ... facts and statistics here include brain and central nervous system tumors (including spinal cord, pituitary and pineal gland ... U.S. living with a primary brain and central nervous system tumor. This year, nearly 17,000 people will ...

  19. Brain and Spinal Tumors

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Brain and Spinal Tumors Information Page Synonym(s): Spinal Cord ... en Español Additional resources from MedlinePlus What are Brain and Spinal Tumors? Tumors of the brain and ...

  20. Childhood Brain Tumors

    MedlinePlus

    ... They are among the most common types of childhood cancers. Some are benign tumors, which aren't ... can still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches ...

  1. The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor

    PubMed Central

    de Melo, Suely Maymone; Bittencourt, Simone; Ferrazoli, Enéas Galdini; da Silva, Clivandir Severino; da Cunha, Flavia Franco; da Silva, Flavia Helena; Stilhano, Roberta Sessa; Denapoli, Priscila Martins Andrade; Zanetti, Bianca Ferrarini; Martin, Priscila Keiko Matsumoto; Silva, Leonardo Martins; dos Santos, Adara Aurea; Baptista, Leandra Santos; Longo, Beatriz Monteiro; Han, Sang Won

    2015-01-01

    Glioblastoma (GBM) is an infiltrative tumor that is difficult to eradicate. Treating GBM with mesenchymal stem cells (MSCs) that have been modified with the HSV-Tk suicide gene has brought significant advances mainly because MSCs are chemoattracted to GBM and kill tumor cells via a bystander effect. To use this strategy, abundantly present adipose-tissue-derived mesenchymal stem cells (AT-MSCs) were evaluated for the treatment of GBM in mice. AT-MSCs were prepared using a mechanical protocol to avoid contamination with animal protein and transduced with HSV-Tk via a lentiviral vector. The U-87 glioblastoma cells cultured with AT-MSC-HSV-Tk died in the presence of 25 or 50 μM ganciclovir (GCV). U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm2 after 4 weeks, but the injection of AT-MSC-HSV-Tk cells one week after the U-87 injection, combined with GCV treatment, drastically reduced tumors to smaller than 0.5 mm2. Immunohistochemical analysis of the tumors showed the presence of AT-MSC-HSV-Tk cells only within the tumor and its vicinity, but not in other areas of the brain, showing chemoattraction between them. The abundance of AT-MSCs and the easier to obtain them mechanically are strong advantages when compared to using MSCs from other tissues. PMID:26067671

  2. Brain tumor - children

    MedlinePlus

    Glioblastoma multiforme - children; Ependymoma - children; Glioma - children; Astrocytoma - children; Medulloblastoma - children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children)

  3. Tissue Factor Regulation by miR-520g in Primitive Neuronal Brain Tumor Cells: A Possible Link between Oncomirs and the Vascular Tumor Microenvironment.

    PubMed

    D'Asti, Esterina; Huang, Annie; Kool, Marcel; Meehan, Brian; Chan, Jennifer A; Jabado, Nada; Korshunov, Andrey; Pfister, Stefan M; Rak, Janusz

    2016-02-01

    Pediatric embryonal brain tumors with multilayered rosettes demonstrate a unique oncogenic amplification of the chromosome 19 miRNA cluster, C19MC. Because oncogenic lesions often cause deregulation of vascular effectors, including procoagulant tissue factor (TF), this study explores whether there is a link between C19MC oncogenic miRNAs (oncomirs) and the coagulant properties of cancer cells, a question previously not studied. In a pediatric embryonal brain tumor tissue microarray, we observed an association between C19MC amplification and reduced fibrin content and TF expression, indicative of reduced procoagulant activity. In medulloblastoma cell lines (DAOY and UW228) engineered to express miR-520g, a biologically active constituent of the C19MC cluster, we observed reduced TF expression, procoagulant and TF signaling activities (responses to factor VIIa stimulation), and diminished TF emission as cargo of extracellular vesicles. Antimir and luciferase reporter assays revealed a specific and direct effect of miR-520g on the TF 3' untranslated region. Although the endogenous MIR520G locus is methylated in differentiated cells, exposure of DAOY cells to 5-aza-2'-deoxycytidine or their growth as stem cell-like spheres up-regulated endogenous miR-520g with a coincident reduction in TF expression. We propose that the properties of tumors harboring oncomirs may include unique alterations of the vascular microenvironment, including deregulation of TF, with a possible impact on the biology, therapy, and hemostatic adverse effects of both disease progression and treatment. PMID:26687818

  4. Modern Brain Tumor Imaging

    PubMed Central

    Barajas, Ramon F.; Cha, Soonmee

    2015-01-01

    The imaging and clinical management of patients with brain tumor continue to evolve over time and now heavily rely on physiologic imaging in addition to high-resolution structural imaging. Imaging remains a powerful noninvasive tool to positively impact the management of patients with brain tumor. This article provides an overview of the current state-of-the art clinical brain tumor imaging. In this review, we discuss general magnetic resonance (MR) imaging methods and their application to the diagnosis of, treatment planning and navigation, and disease monitoring in patients with brain tumor. We review the strengths, limitations, and pitfalls of structural imaging, diffusion-weighted imaging techniques, MR spectroscopy, perfusion imaging, positron emission tomography/MR, and functional imaging. Overall this review provides a basis for understudying the role of modern imaging in the care of brain tumor patients. PMID:25977902

  5. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    SciTech Connect

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

    2015-06-15

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

  6. Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging.

    PubMed

    Wu, Qiaoyi; Wu, Liang; Wang, Yuzhe; Zhu, Zhi; Song, Yanling; Tan, Yuyu; Wang, Xing-Fu; Li, Jiuxing; Kang, Dezhi; Yang, Chaoyong James

    2016-06-15

    Gliosarcoma, a variant of glioblastoma multiforme (GBM), is a highly invasive malignant tumor. Unfortunately, this disease still marked by poor prognosis regardless of modern treatments. It is of great significance to discover specific molecular probes targeting gliosarcoma for early cancer diagnosis and therapy. Herein, we have selected a group of DNA aptamers with high affinity and selectivity against gliosarcoma cells K308 using cell-SELEX. All the dissociation constants of these aptamers against gliosarcoma cells were in the nanomolar range and aptamer WQY-9 has the highest affinity and good selectivity among them. Furthermore, truncated aptamer sequence, WQY-9-B, shows similar recognition ability to aptamer WQY-9. In addition, WQY-9-B was found to be able to bind selectively and internalize into cytoplasm of target cancer cell at 37 °C. More importantly, compared to a random sequence, aptamer WQY-9-B showed excellent recognition rate (73.3%) for tissue sections of clinical gliosarcoma samples. These data suggests that aptamer WQY-9-B has excellent potential as an effective molecular probe for gliosarcoma diagnosis. PMID:26802746

  7. Epilepsy and brain tumors.

    PubMed

    Englot, Dario J; Chang, Edward F; Vecht, Charles J

    2016-01-01

    Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70-80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60-75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20-50% of patients with meningioma and 20-35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60-90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

  8. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies. PMID:20370314

  9. Aquaporins and Brain Tumors.

    PubMed

    Maugeri, Rosario; Schiera, Gabriella; Di Liegro, Carlo Maria; Fricano, Anna; Iacopino, Domenico Gerardo; Di Liegro, Italia

    2016-01-01

    Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood-brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID:27367682

  10. Aquaporins and Brain Tumors

    PubMed Central

    Maugeri, Rosario; Schiera, Gabriella; Di Liegro, Carlo Maria; Fricano, Anna; Iacopino, Domenico Gerardo; Di Liegro, Italia

    2016-01-01

    Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood–brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization of different isoforms of aquaporins (AQPs), a family of water channels, some of which are also involved in the transport of other small molecules, such as glycerol and urea. In this review, we discuss relationships among expression/localization of AQPs and brain tumors/edema, also focusing on the possible role of these molecules as both diagnostic biomarkers of cancer progression, and therapeutic targets. Finally, we will discuss the possibility that AQPs, together with other cancer promoting factors, can be exchanged among brain cells via extracellular vesicles (EVs). PMID:27367682

  11. Brain Tumor Risk Factors

    MedlinePlus

    ... to the genes can be called “genetic.” However, only about 5 to 10 percent of all cancer is hereditary (ie, passed down from one generation to another in a family). In cases of hereditary brain tumors, a mutation, or change in the DNA ...

  12. Living with a Brain Tumor

    MedlinePlus

    ... Mentor The ABTA's Online Support Community Understanding The Affordable Care Act Living with a Brain Tumor Understanding Emotions Talking ... Mentor The ABTA's Online Support Community Understanding The Affordable Care Act Living with a Brain Tumor Understanding Emotions Talking ...

  13. Drugs Approved for Brain Tumors

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Brain Tumors This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Brain Tumors Afinitor (Everolimus) Afinitor Disperz (Everolimus) Avastin (Bevacizumab) ...

  14. Brain tumors in infants

    PubMed Central

    Ghodsi, Seyyed Mohammad; Habibi, Zohreh; Hanaei, Sara; Moradi, Ehsan; Nejat, Farideh

    2015-01-01

    Background: Brain tumors in infants have different clinical presentations, anatomical distribution, histopathological diagnosis, and clinical prognosis compared with older children. Materials and Methods: A retrospective analysis was done in patients <12 months old who were operated on for primary brain tumor in Children's Hospital Medical Center since 2008 to 2014. Results: Thirty-one infants, 20 males and 11 females, with the mean age of 7.13 months (0.5–12) were enrolled. There were 16 supratentorial and 15 infratentorial tumors. The presenting symptoms included increased head circumference (16); bulge fontanel (15); vomiting (15); developmental regression (11); sunset eye (7); seizure (4); loss of consciousness (4); irritability (3); nystagmus (2); visual loss (2); hemiparesis (2); torticollis (2); VI palsy (3); VII, IX, X nerve palsy (each 2); and ptosis (1). Gross total and subtotal resection were performed in 19 and 11 cases, respectively. Fourteen patients needed external ventricular drainage in the perioperative period, from whom four infants required a ventriculoperitoneal shunt. One patient underwent ventriculoperitoneal shunting without tumor resection. The most common histological diagnoses were primitive neuroectodermal tumor (7), followed by anaplastic ependymoma (6) and grade II ependymoma. The rate of 30-day mortality was 19.3%. Eighteen patients are now well-controlled with or without adjuvant therapy (overall survival; 58%), from whom 13 cases are tumor free (disease free survival; 41.9%), 3 cases have residual masses with fixed or decreased size (progression-free survival; 9.6%), and 2 cases are still on chemotherapy. Conclusion: Brain tumors in infants should be treated with surgical resection, followed by chemotherapy when necessary. PMID:26962338

  15. Effect of Heterogeneity of Tissues on RF Energy Absorption in the Brain for Exposure Assessment in Epidemiological Studies on Mobile Phone Use and Brain Tumors

    NASA Astrophysics Data System (ADS)

    Varsier, Nadege; Wake, Kanako; Taki, Masao; Watanabe, Soichi

    We compared SAR distributions in major anatomical structures of the brain of a homogeneous and a heterogeneous model using FDTD calculations. Our results proved a good correlation between SAR values in lobes of the brain where tumors may arise more frequently. However SAR values at some specific locations were shown to be under or overestimated.

  16. Irradiation-injured brain tissues can self-renew in the absence of the pivotal tumor suppressor p53 in the medaka (Oryzias latipes) embryo

    PubMed Central

    Yasuda, Takako; Kimori, Yoshitaka; Nagata, Kento; Igarashi, Kento; Watanabe-Asaka, Tomomi; Oda, Shoji; Mitani, Hiroshi

    2016-01-01

    The tumor suppressor protein, p53, plays pivotal roles in regulating apoptosis and proliferation in the embryonic and adult central nervous system (CNS) following neuronal injuries such as those induced by ionizing radiation. There is increasing evidence that p53 negatively regulates the self-renewal of neural stem cells in the adult murine brain; however, it is still unknown whether p53 is essential for self-renewal in the injured developing CNS. Previously, we demonstrated that the numbers of apoptotic cells in medaka (Oryzias latipes) embryos decreased in the absence of p53 at 12–24 h after irradiation with 10-Gy gamma rays. Here, we used histology to examine the later morphological development of the irradiated medaka brain. In p53-deficient larvae, the embryonic brain possessed similar vacuoles in the brain and retina, although the vacuoles were much smaller and fewer than those found in wild-type embryos. At the time of hatching (6 days after irradiation), no brain abnormality was observed. In contrast, severe disorganized neuronal arrangements were still present in the brain of irradiated wild-type embryos. Our present results demonstrated that self-renewal of the brain tissue completed faster in the absence of p53 than wild type at the time of hatching because p53 reduces the acute severe neural apoptosis induced by irradiation, suggesting that p53 is not essential for tissue self-renewal in developing brain. PMID:26410759

  17. Spectromicroscopy of Brain Tissue

    NASA Astrophysics Data System (ADS)

    Frazer, Bradley; Cannara, Rachel; Gilbert, Benjamin; Destasio, Gelsomina; Ogg, Mandy; Gough, Kathy

    2001-03-01

    X-ray PhotoElectron Emission Microscopy (X-PEEM) was originally developed for studying the surface microchemistry of materials science specimens. It has then evolved into a valuable tool to investigate the magnetic properties of materials and the microchemistry of cells and tissues. We used the MEPHISTO X-PEEM instrument, installed at the UW-Synchrotron Radiation Center to detect trace concentrations of non-physiological elements in senile brain tissue specimens. These tissues contain a large number of plaques, in which all the compounds and elements that the brain does not need are disposed and stored. We hypothesized that plaques should contain elements, such as Si, B, and Al which are very abundant on the Earth crust but absent from healthy tissues. We verified this hypothesis with MEPHISTO and found evidence of Si and B, and suspect Al. We also found a higher than normal concentration of Fe.

  18. Automatic brain tumor segmentation

    NASA Astrophysics Data System (ADS)

    Clark, Matthew C.; Hall, Lawrence O.; Goldgof, Dmitry B.; Velthuizen, Robert P.; Murtaugh, F. R.; Silbiger, Martin L.

    1998-06-01

    A system that automatically segments and labels complete glioblastoma-multiform tumor volumes in magnetic resonance images of the human brain is presented. The magnetic resonance images consist of three feature images (T1- weighted, proton density, T2-weighted) and are processed by a system which integrates knowledge-based techniques with multispectral analysis and is independent of a particular magnetic resonance scanning protocol. Initial segmentation is performed by an unsupervised clustering algorithm. The segmented image, along with cluster centers for each class are provided to a rule-based expert system which extracts the intra-cranial region. Multispectral histogram analysis separates suspected tumor from the rest of the intra-cranial region, with region analysis used in performing the final tumor labeling. This system has been trained on eleven volume data sets and tested on twenty-two unseen volume data sets acquired from a single magnetic resonance imaging system. The knowledge-based tumor segmentation was compared with radiologist-verified `ground truth' tumor volumes and results generated by a supervised fuzzy clustering algorithm. The results of this system generally correspond well to ground truth, both on a per slice basis and more importantly in tracking total tumor volume during treatment over time.

  19. Mature brain tissue in the sacrococcygeal region.

    PubMed

    Shrestha, Binod Bade; Ghimire, Pradeep; Ghartimagar, Dilasma; Jwarchan, Bishnu; Lalchan, Subita; Karmacharya, Mikesh

    2016-01-01

    Complete mature brain tissue in sacrococcygeal region is a rare congenital anomaly in a newborn, which usually is misdiagnosed for sacrococcygeal teratoma. Glial tumor-like ependymoma is also common in sacrococcygeal area but mostly appears later in life. We present a case of complete heterotopic brain tissue in the sacrococcygeal region. The patient underwent total excision of mass with coccygectomy. To our knowledge it is the second case being reported. PMID:27194682

  20. Mature brain tissue in the sacrococcygeal region

    PubMed Central

    Shrestha, Binod Bade; Ghimire, Pradeep; Ghartimagar, Dilasma; Jwarchan, Bishnu; Lalchan, Subita; Karmacharya, Mikesh

    2016-01-01

    Complete mature brain tissue in sacrococcygeal region is a rare congenital anomaly in a newborn, which usually is misdiagnosed for sacrococcygeal teratoma. Glial tumor-like ependymoma is also common in sacrococcygeal area but mostly appears later in life. We present a case of complete heterotopic brain tissue in the sacrococcygeal region. The patient underwent total excision of mass with coccygectomy. To our knowledge it is the second case being reported. PMID:27194682

  1. MRI and MRS of human brain tumors.

    PubMed

    Hou, Bob L; Hu, Jiani

    2009-01-01

    The purpose of this chapter is to provide an introduction to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of human brain tumors, including the primary applications and basic terminology involved. Readers who wish to know more about this broad subject should seek out the referenced books (1. Tofts (2003) Quantitative MRI of the brain. Measuring changes caused by disease. Wiley; Bradley and Stark (1999) 2. Magnetic resonance imaging, 3rd Edition. Mosby Inc; Brown and Semelka (2003) 3. MRI basic principles and applications, 3rd Edition. Wiley-Liss) or reviews (4. Top Magn Reson Imaging 17:127-36, 2006; 5. JMRI 24:709-724, 2006; 6. Am J Neuroradiol 27:1404-1411, 2006).MRI is the most popular means of diagnosing human brain tumors. The inherent difference in the magnetic resonance (MR) properties of water between normal tissues and tumors results in contrast differences on the image that provide the basis for distinguishing tumors from normal tissues. In contrast to MRI, which provides spatial maps or images using water signals of the tissues, proton MRS detects signals of tissue metabolites. MRS can complement MRI because the observed MRS peaks can be linked to inherent differences in biochemical profiles between normal tissues and tumors.The goal of MRI and MRS is to characterize brain tumors, including tumor core, edge, edema, volume, types, and grade. The commonly used brain tumor MRI protocol includes T2-weighted images and T1-weighted images taken both before and after the injection of a contrast agent (typically gadolinium: Gd). The commonly used MRS technique is either point-resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM). PMID:19381963

  2. Brain Tumor Epidemiology Consortium (BTEC)

    Cancer.gov

    The Brain Tumor Epidemiology Consortium is an open scientific forum organized to foster the development of multi-center, international and inter-disciplinary collaborations that will lead to a better understanding of the etiology, outcomes, and prevention of brain tumors.

  3. Intra-axial brain tumors.

    PubMed

    Rapalino, Otto; Batchelor, Tracy; González, R Gilberto

    2016-01-01

    There is a wide variety of intra-axial primary and secondary brain neoplasms. Many of them have characteristic imaging features while other tumors can present in a similar fashion. There are peculiar posttreatment imaging phenomena that can present as intra-axial mass-like lesions (such as pseudoprogression or radiation necrosis), further complicating the diagnosis and clinical follow-up of patients with intracerebral tumors. The purpose of this chapter is to present a general overview of the most common intra-axial brain tumors and peculiar posttreatment changes that are very important in the diagnosis and clinical follow-up of patients with brain tumors. PMID:27432670

  4. [Imaging of childhood brain tumors].

    PubMed

    Couanet, D; Adamsbaum, C

    2006-06-01

    Brain tumors represent around a quarter of all solid tumors observed in the pediatric population. Infratentorial tumors are the most frequent, mostly encountered between 4 and 11 years of age. Early imaging is important because initial symptoms can be misinterpreted as statural and pubertal disorders or pseudoabdominal symptoms with apathy and vomiting in infants. Because signal abnormalities on MRI are most often not specific, it is essential to take into account the clinical and topographic characteristics of the lesion to establish an appropriate differential diagnosis. The main patterns of brain tumors observed in pediatrics are presented. Brain metastases are very unusual in children, in contrast to lepto-meningeal metastasis. PMID:16778744

  5. Childhood Brain Tumor Epidemiology: A Brain Tumor Epidemiology Consortium Review

    PubMed Central

    Johnson, Kimberly J.; Cullen, Jennifer; Barnholtz-Sloan, Jill S.; Ostrom, Quinn T.; Langer, Chelsea E.; Turner, Michelle C.; McKean-Cowdin, Roberta; Fisher, James L.; Lupo, Philip J.; Partap, Sonia; Schwartzbaum, Judith A.; Scheurer, Michael E.

    2014-01-01

    Childhood brain tumors are the most common pediatric solid tumor and include several histological subtypes. Although progress has been made in improving survival rates for some subtypes, understanding of risk factors for childhood brain tumors remains limited to a few genetic syndromes and ionizing radiation to the head and neck. In this report, we review descriptive and analytical epidemiology childhood brain tumor studies from the past decade and highlight priority areas for future epidemiology investigations and methodological work that is needed to advance our understanding of childhood brain tumor causes. Specifically, we summarize the results of a review of studies published since 2004 that have analyzed incidence and survival in different international regions and that have examined potential genetic, immune system, developmental and birth characteristics, and environmental risk factors. PMID:25192704

  6. Pediatric Brain Tumors: An Update.

    PubMed

    Segal, Devorah; Karajannis, Matthias A

    2016-07-01

    Brain tumors collectively represent the most common solid tumors in childhood and account for significant morbidity and mortality. Until recently, pediatric brain tumors were diagnosed and classified solely based on histologic criteria, and treatments were chosen empirically. Recent research has greatly enhanced our understanding of the diverse biology of pediatric brain tumors, their molecular and genetic underpinnings, leading to improved diagnostic accuracy and risk stratification, as well as the development of novel biomarkers and molecular targeted therapies. For subsets of patients, these new treatment options have already resulted in improved survival and decreased treatment toxicity. In this article, we provide an overview of the most common childhood brain tumors, describe recent key advances in the field, and discuss the therapeutic challenges that remain. PMID:27230809

  7. Intensity-modulated radiotherapy for gliomas:dosimetric effects of changes in gross tumor volume on organs at risk and healthy brain tissue

    PubMed Central

    Yang, Zhen; Zhang, Zijian; Wang, Xia; Hu, Yongmei; Lyu, Zhiping; Huo, Lei; Wei, Rui; Fu, Jun; Hong, Jidong

    2016-01-01

    Aim The aim of this study was to explore the effects of changes in the gross tumor volume (GTV) on dose distribution in organs at risk (OARs) and healthy brain tissue in patients with gliomas. Methods Eleven patients suffering from gliomas with intensity-modulated radiotherapy (IMRT) plans treated with a simultaneous integrated boost technique planned before therapy (initial plans) were prospectively enrolled. At the end of radiotherapy, patients underwent repeat computed tomography and magnetic resonance imaging, and IMRT was replanned. The GTV and dosimetric parameters between the initial and replanned IMRT were compared using the Wilcoxon two-related-sample test, and correlations between the initial GTV and the replanned target volumes were assessed using the bivariate correlation test. Results The volume of the residual tumor did not change significantly (P>0.05), the volume of the surgical cavity decreased significantly (P<0.05), and the GTV and target volumes decreased significantly at the end of IMRT (all P<0.05). The near-maximum dose to OARs and volumes of healthy brain tissue receiving total doses of 10–50 Gy were lower in the replanned IMRT than in the initial IMRT (all P<0.05). The GTV in the initial plan was significantly positively correlated with the changes in the GTV and planning target volume 1 that occurred during IMRT (all P<0.05). Conclusion The reduction in the GTV in patients with gliomas resulted from shrinkage of the surgical cavity during IMRT, leading to decreased doses to the OARs and healthy brain tissue. Such changes appeared to be most meaningful in patients with large initial GTV values. PMID:27366091

  8. Radiosurgery for Pediatric Brain Tumors.

    PubMed

    Murphy, Erin S; Chao, Samuel T; Angelov, Lilyana; Vogelbaum, Michael A; Barnett, Gene; Jung, Edward; Recinos, Violette R; Mohammadi, Alireza; Suh, John H

    2016-03-01

    The utility of radiosurgery for pediatric brain tumors is not well known. For children, radiosurgery may have an important role for treating unresectable tumors, residual disease, or tumors in the recurrent setting that have received prior radiotherapy. The available evidence demonstrates utility for some children with primary brain tumors resulting in good local control. Radiosurgery can be considered for limited residual disease or focal recurrences. However, the potential toxicities are unique and not insignificant. Therefore, prospective studies need to be performed to develop guidelines for indications and treatment for children and reduce toxicity in this population. PMID:26536284

  9. Dendrimer technologies for brain tumor.

    PubMed

    Mishra, Vijay; Kesharwani, Prashant

    2016-05-01

    Despite low prevalence, brain tumors are one of the most lethal forms of cancer. Unfortunately the blood-brain barrier (BBB), a highly regulated, well coordinated and efficient barrier, checks the permeation of most of the drugs across it. Hence, crossing this barrier is one of the most significant challenges in the development of efficient central nervous system therapeutics. Surface-engineered dendrimers improve biocompatibility, drug-release kinetics and aptitude to target the BBB and/or tumors and facilitate transportation of anticancer bioactives across the BBB. This review sheds light on different aspects of brain tumors and dendrimers based on different approaches for treatment including recent research, opportunities and challenges encountered in development of novel and efficient dendrimer-based therapeutics for the treatment of brain tumors. PMID:26891979

  10. Monitoring therapeutic monoclonal antibodies in brain tumor

    PubMed Central

    Ait-Belkacem, Rima; Berenguer, Caroline; Villard, Claude; Ouafik, L’Houcine; Figarella-Branger, Dominique; Beck, Alain; Chinot, Olivier; Lafitte, Daniel

    2014-01-01

    Bevacizumab induces normalization of abnormal blood vessels, making them less leaky. By binding to vascular endothelial growth factor, it indirectly attacks the vascular tumor mass. The optimal delivery of targeted therapies including monoclonal antibodies or anti-angiogenesis drugs to the target tissue highly depends on the blood-brain barrier permeability. It is therefore critical to investigate how drugs effectively reach the tumor. In situ investigation of drug distribution could provide a better understanding of pharmacological agent action and optimize chemotherapies for solid tumors. We developed an imaging method coupled to protein identification using matrix-assisted laser desorption/ionization mass spectrometry. This approach monitored bevacizumab distribution within the brain structures, and especially within the tumor, without any labeling. PMID:25484065

  11. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Brain and Spinal Cord Tumors in Adults Download Printable ... the topics below to get started. What Is Brain/CNS Tumors In Adults? What are adult brain ...

  12. Canine spontaneous brain tumors: A large animal model for BNCT

    SciTech Connect

    Gavin, P.R.; Kraft, S.L.; Wendling, L.R.; Miller, D.L.

    1988-01-01

    Brain tumors occur spontaneously on dogs with an incidence similar to that in humans. Brain tumors of dogs have histologic, radiologic, and other diagnostic similarities to human brain tumors. Tumor kinetics and biologic behavior of these tumors in dogs are also similar to that in man. Recent studies indicate that conventional radiation therapy of brain tumors of dogs result in a survival interval appropriate to study the late radiation reactions in the surrounding normal brain and other tissues within the irradiated field. The relatively large size of the dog allows identical diagnostic and therapeutic modalities and methodology. The dog's head size enables the complex dosimetric variables to be relevant to that found in human radiation therapy. For these reasons, spontaneous brain tumors in the dog are an excellent model to study neuon capture theory (NCT). 7 refs., 1 fig., 3 tabs.

  13. CARS and non-linear microscopy imaging of brain tumors

    NASA Astrophysics Data System (ADS)

    Galli, Roberta; Uckermann, Ortrud; Tamosaityte, Sandra; Geiger, Kathrin; Schackert, Gabriele; Steiner, Gerald; Koch, Edmund; Kirsch, Matthias

    2013-06-01

    Nonlinear optical microscopy offers a series of techniques that have the potential to be applied in vivo, for intraoperative identification of tumor border and in situ pathology. By addressing the different content of lipids that characterize the tumors with respect to the normal brain tissue, CARS microscopy enables to discern primary and secondary brain tumors from healthy tissue. A study performed in mouse models shows that the reduction of the CARS signal is a reliable quantity to identify brain tumors, irrespective from the tumor type. Moreover it enables to identify tumor borders and infiltrations at a cellular resolution. Integration of CARS with autogenous TPEF and SHG adds morphological and compositional details about the tissue. Examples of multimodal CARS imaging of different human tumor biopsies demonstrate the ability of the technique to retrieve information useful for histopathological diagnosis.

  14. Extra-axial brain tumors.

    PubMed

    Rapalino, Otto; Smirniotopoulos, James G

    2016-01-01

    Extra-axial brain tumors are the most common adult intracranial neoplasms and encompass a broad spectrum of pathologic subtypes. Meningiomas are the most common extra-axial brain tumor (approximately one-third of all intracranial neoplasms) and typically present as slowly growing dural-based masses. Benign meningiomas are very common, and may occasionally be difficult to differentiate from more aggressive subtypes (i.e., atypical or malignant varieties) or other dural-based masses with more aggressive biologic behavior (e.g., hemangiopericytoma or dural-based metastases). Many neoplasms that typically affect the brain parenchyma (intra-axial), such as gliomas, may also present with primary or secondary extra-axial involvement. This chapter provides a general and concise overview of the common types of extra-axial tumors and their typical imaging features. PMID:27432671

  15. Cytogenetics of human brain tumors

    SciTech Connect

    Finkernagel, S.W.; Kletz, T.; Day-Salvatore, D.L.

    1994-09-01

    Chromosome studies of 55 brain tumors, including meningiomas, gliomas, astrocyomas and pituatary adenomas, were performed. Primary and first passage cultures were successfully obtained in 75% of these samples with an average of 18 G-banded metaphases analyzed per tumor. 44% of all the brain tumors showed numerical and or structural abnormalities. 46% of the primary and 38% of the first passage cultures showed similar numerical gains/losses and complex karyotypic changes. The most frequent numerical abnormalities (n {ge} 5) included loss of chromosomes 10, 22, and Y. The structural abnormalities most often seen involved 1p, 2, 5, 7, 17q and 19. This is an ongoing study which will attempt to correlate tumor type with specific karyotypic changes and to see if any of the observed chromosomal abnormalities provide prognostic indicators.

  16. A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus - tumor association.

    PubMed

    Strong, Michael J; Blanchard, Eugene; Lin, Zhen; Morris, Cindy A; Baddoo, Melody; Taylor, Christopher M; Ware, Marcus L; Flemington, Erik K

    2016-01-01

    Next generation sequencing (NGS) can globally interrogate the genetic composition of biological samples in an unbiased yet sensitive manner. The objective of this study was to utilize the capabilities of NGS to investigate the reported association between glioblastoma multiforme (GBM) and human cytomegalovirus (HCMV). A large-scale comprehensive virome assessment was performed on publicly available sequencing datasets from the Cancer Genome Atlas (TCGA), including RNA-seq datasets from primary GBM (n = 157), recurrent GBM (n = 13), low-grade gliomas (n = 514), recurrent low-grade gliomas (n = 17), and normal brain (n = 5), and whole genome sequencing (WGS) datasets from primary GBM (n = 51), recurrent GBM (n = 10), and normal matched blood samples (n = 20). In addition, RNA-seq datasets from MRI-guided biopsies (n = 92) and glioma stem-like cell cultures (n = 9) were analyzed. Sixty-four DNA-seq datasets from 11 meningiomas and their corresponding blood control samples were also analyzed. Finally, three primary GBM tissue samples were obtained, sequenced using RNA-seq, and analyzed. After in-depth analysis, the most robust virus findings were the detection of papillomavirus (HPV) and hepatitis B reads in the occasional LGG sample (4 samples and 1 sample, respectively). In addition, low numbers of virus reads were detected in several datasets but detailed investigation of these reads suggest that these findings likely represent artifacts or non-pathological infections. For example, all of the sporadic low level HCMV reads were found to map to the immediate early promoter intimating that they likely originated from laboratory expression vector contamination. Despite the detection of low numbers of Epstein-Barr virus reads in some samples, these likely originated from infiltrating B-cells. Finally, human herpesvirus 6 and 7 aligned viral reads were identified in all DNA-seq and a few RNA-seq datasets but detailed analysis

  17. Brain tumors in irradiated monkeys.

    NASA Technical Reports Server (NTRS)

    Haymaker, W.; Miquel, J.; Rubinstein, L. J.

    1972-01-01

    A study was made of 32 monkeys which survived one to seven years after total body exposure to protons or to high-energy X rays. Among these 32 monkeys there were 21 which survived two years or longer after exposure to 200 to 800 rad. Glioblastoma multiforme developed in 3 of the 10 monkeys surviving three to five years after receiving 600 or 800 rad 55-MeV protons. Thus, the incidence of tumor development in the present series was far higher than the incidence of spontaneously developing brain tumors in monkeys cited in the literature. This suggests that the tumors in the present series may have been radiation-induced.

  18. Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

    PubMed Central

    Cheng, Yu; Morshed, Ramin; Auffinger, Brenda; Tobias, Alex L.; Lesniak, Maciej S.

    2013-01-01

    Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management. PMID:24060923

  19. Multifunctional nanoparticles for brain tumor imaging and therapy.

    PubMed

    Cheng, Yu; Morshed, Ramin A; Auffinger, Brenda; Tobias, Alex L; Lesniak, Maciej S

    2014-02-01

    Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management. PMID:24060923

  20. Cytodiagnosis of soft tissue tumors.

    PubMed

    Oland, J; Rosen, A; Reif, R; Sayfan, J; Orda, R

    1988-03-01

    The only acceptable definitive diagnosis of a soft tissue mass is histologic or cytologic examination. In recent years, fine-needle aspiration cytology is used in more and more centers for diagnosis of soft tissue masses. We studied 196 aspiration cytologies performed on soft tissue lesions. Out of these, in 48 cases a definitive surgical procedure or open biopsy for histology and further evaluation were performed. There were 25 sarcomas and 23 benign tumors. There was one false negative cytologic result in this group; no false positive cytologies were detected. It seems that cytodiagnosis of soft tissue masses performed by an experienced pathologist is the method of choice, permitting a good diagnostic evaluation, with almost none of the traumatic and oncologic disadvantages of the other methods of biopsy. PMID:3352270

  1. More Complete Removal of Malignant Brain Tumors by Fluorescence-Guided Surgery

    ClinicalTrials.gov

    2016-05-13

    Benign Neoplasms, Brain; Brain Cancer; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Brain Tumor, Recurrent; Brain Tumors; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas; Glioblastoma

  2. Photoacoustic Measurements in Brain Tissue

    SciTech Connect

    Kasili, P.M.; Mobley, J.; Vo-Dinh, T.

    1999-09-19

    In this work, we develop and evaluate the photoacoustic technique for recording spectra of white and gray mammalian brain tissues. In addition to the experimental work, we also discuss the geometric aspects of photoacoustic signal generation using collimated light. Spectra constructed from the peak-to-peak amplitude of the photoacoustic waveforms indicate differences in the two tissue types at wavelengths between 620 and 695 nm. The potential of the technique for non-invasive diagnosis is discussed.

  3. Deregulated proliferation and differentiation in brain tumors.

    PubMed

    Swartling, Fredrik J; Čančer, Matko; Frantz, Aaron; Weishaupt, Holger; Persson, Anders I

    2015-01-01

    Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment resistance, suppress tumor growth, and prevent recurrence in patients. PMID:25416506

  4. Deregulated proliferation and differentiation in brain tumors

    PubMed Central

    Swartling, Fredrik J; Čančer, Matko; Frantz, Aaron; Weishaupt, Holger; Persson, Anders I

    2014-01-01

    Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment-resistance, suppress tumor growth, and prevent recurrence in patients. PMID:25416506

  5. Primary Neuroendocrine Tumor in Brain

    PubMed Central

    Tamura, Ryota; Kuroshima, Yoshiaki; Nakamura, Yoshiki

    2014-01-01

    The incidence of brain metastases for neuroendocrine tumor (NET) is reportedly 1.5~5%, and the origin is usually pulmonary. A 77-year-old man presented to our hospital with headache and disturbance of specific skilled motor activities. Computed tomography (CT) showed a massive neoplastic lesion originating in the left temporal and parietal lobes that caused a mass edematous effect. Grossly, total resection of the tumor was achieved. Histological examination revealed much nuclear atypia and mitotic figures. Staining for CD56, chromogranin A, and synaptophysin was positive, indicating NET. The MIB-1 index was 37%. Histopathologically, the tumor was diagnosed as NET. After surgery, gastroscopy and colonoscopy were performed, but the origin was not seen. After discharge, CT and FDG-PET (fluoro-2-deoxy-d-glucose positron emission tomography) were performed every 3 months. Two years later we have not determined the origin of the tumor. It is possible that the brain is the primary site of this NET. To our knowledge, this is the first reported case of this phenomenon. PMID:25506006

  6. [MR spectroscopy in brain tumors].

    PubMed

    Papanagiotou, P; Backens, M; Grunwald, I Q; Farmakis, G; Politi, M; Roth, C; Reith, W

    2007-06-01

    MRT allows the anatomical visualization of intracerebral space-occupying lesions, and when magnetic resonance spectroscopy (MRS) is used in routine clinical practice it can give more information and be helpful in the diagnosis of such lesions. In MRS with long echo times for nerve tissue there are five metabolites that are particularly significant: N-acetyl aspartate (NAA), creatine, choline, lactate, and lipids. NAA levels are lowered in the presence of intracerebral tumors. Creatine is lowered in situations of hypermetabolic metabolism and elevated in hypometabolic conditions, but remains constant in many pathologic states and can be used as a reliable reference value. With malignant tumors there are usually elevated choline concentrations, reflecting increased membrane synthesis and a higher cell turnover. The lactate level rises following a switch in metabolism from aerobic to anaerobic glycolysis, and this is frequently observed in the presence of malignant tumors. The occurrence of lipid peaks in a tumor spectrum suggests the presence of tissue necroses or metastases. There are typical constellations that are seen on MRS for individual tumors, which are discussed in detail in the present paper. PMID:17530212

  7. State of the art survey on MRI brain tumor segmentation.

    PubMed

    Gordillo, Nelly; Montseny, Eduard; Sobrevilla, Pilar

    2013-10-01

    Brain tumor segmentation consists of separating the different tumor tissues (solid or active tumor, edema, and necrosis) from normal brain tissues: gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). In brain tumor studies, the existence of abnormal tissues may be easily detectable most of the time. However, accurate and reproducible segmentation and characterization of abnormalities are not straightforward. In the past, many researchers in the field of medical imaging and soft computing have made significant survey in the field of brain tumor segmentation. Both semiautomatic and fully automatic methods have been proposed. Clinical acceptance of segmentation techniques has depended on the simplicity of the segmentation, and the degree of user supervision. Interactive or semiautomatic methods are likely to remain dominant in practice for some time, especially in these applications where erroneous interpretations are unacceptable. This article presents an overview of the most relevant brain tumor segmentation methods, conducted after the acquisition of the image. Given the advantages of magnetic resonance imaging over other diagnostic imaging, this survey is focused on MRI brain tumor segmentation. Semiautomatic and fully automatic techniques are emphasized. PMID:23790354

  8. Antiangiogenic therapy in brain tumors

    PubMed Central

    Lakka, Sajani S; Rao, Jasti S

    2008-01-01

    Angiogenesis, the recruitment of new blood vessels, is an essential component of tumor progression. Malignant brain tumors are highly vascularized and their growth is angiogenesis-dependent. As such, inhibition of the sprouting of new capillaries from pre-existing blood vessels is one of the most promising antiglioma therapeutic approaches. Numerous classes of molecules have been implicated in regulating angiogenesis and, thus, novel agents that target and counteract angiogenesis are now being developed. The therapeutic trials of a number of angiogenesis inhibitors as antiglioma drugs are currently under intense investigation. Preliminary studies of angiogenic blockade in glioblastoma have been promising and several clinical trials are now underway to develop optimum treatment strategies for antiangiogenic agents. This review will cover state-of-the-art antiangiogenic targets for brain tumor treatment and discuss future challenges. An increased understanding of the angiogenic process, the diversity of its inducers and mediators, appropriate drug schedules and the use of these agents with other modalities may lead to radically new treatment regimens to achieve maximal efficacy. PMID:18928341

  9. Subacute brain atrophy after radiation therapy for malignant brain tumor

    SciTech Connect

    Asai, A.; Matsutani, M.; Kohno, T.; Nakamura, O.; Tanaka, H.; Fujimaki, T.; Funada, N.; Matsuda, T.; Nagata, K.; Takakura, K.

    1989-05-15

    Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

  10. Robotic multimodality stereotactic brain tissue identification: work in progress

    NASA Technical Reports Server (NTRS)

    Andrews, R.; Mah, R.; Galvagni, A.; Guerrero, M.; Papasin, R.; Wallace, M.; Winters, J.

    1997-01-01

    Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

  11. Interstitial irradiation of brain tumors: a review

    SciTech Connect

    Bernstein, M.; Gutin, P.H.

    1981-12-01

    As an adjuvant to surgery, radiation therapy has consistently proven to be the most successful form of treatment for primary and secondary malignant brain tumors and possibly for inoperable benign tumors. Because the risk of radiation necrosis of normal brain limits the amount of radiation that can be given by external beam therapy at conventional dose rates, interstitial radiation of brain tumors is a logical alternative treatment approach. We discuss the radiobiological advantages of low dose rate irradiation and intratumoral placement of sources that make interstitial irradiation an attractive treatment for brain tumors and review the history of clinical brachytherapy for intracranial neoplasia.

  12. Extracellular Vesicles in Brain Tumor Progression.

    PubMed

    D'Asti, Esterina; Chennakrishnaiah, Shilpa; Lee, Tae Hoon; Rak, Janusz

    2016-04-01

    Brain tumors can be viewed as multicellular 'ecosystems' with increasingly recognized cellular complexity and systemic impact. While the emerging diversity of malignant disease entities affecting brain tissues is often described in reference to their signature alterations within the cellular genome and epigenome, arguably these cell-intrinsic changes can be regarded as hardwired adaptations to a variety of cell-extrinsic microenvironmental circumstances. Conversely, oncogenic events influence the microenvironment through their impact on the cellular secretome, including emission of membranous structures known as extracellular vesicles (EVs). EVs serve as unique carriers of bioactive lipids, secretable and non-secretable proteins, mRNA, non-coding RNA, and DNA and constitute pathway(s) of extracellular exit of molecules into the intercellular space, biofluids, and blood. EVs are also highly heterogeneous as reflected in their nomenclature (exosomes, microvesicles, microparticles) attempting to capture their diverse origin, as well as structural, molecular, and functional properties. While EVs may act as a mechanism of molecular expulsion, their non-random uptake by heterologous cellular recipients defines their unique roles in the intercellular communication, horizontal molecular transfer, and biological activity. In the central nervous system, EVs have been implicated as mediators of homeostasis and repair, while in cancer they may act as regulators of cell growth, clonogenicity, angiogenesis, thrombosis, and reciprocal tumor-stromal interactions. EVs produced by specific brain tumor cell types may contain the corresponding oncogenic drivers, such as epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (and hence are often referred to as 'oncosomes'). Through this mechanism, mutant oncoproteins and nucleic acids may be transferred horizontally between cellular populations altering their individual and collective phenotypes. Oncogenic pathways

  13. Brain tumor modeling: glioma growth and interaction with chemotherapy

    NASA Astrophysics Data System (ADS)

    Banaem, Hossein Y.; Ahmadian, Alireza; Saberi, Hooshangh; Daneshmehr, Alireza; Khodadad, Davood

    2011-10-01

    In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

  14. Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors

    PubMed Central

    Wainwright, Derek A.; Sengupta, Sadhak; Han, Yu; Lesniak, Maciej S.

    2011-01-01

    Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an average survival time of 15 months. Previously, we and others demonstrated that CD4+FoxP3+ regulatory T cells (Tregs) infiltrate human GBM as well as mouse models that recapitulate malignant brain tumors. However, whether brain tumor-resident Tregs are thymus-derived natural Tregs (nTregs) or induced Tregs (iTregs), by the conversion of conventional CD4+ T cells, has not been established. To investigate this question, we utilized the i.c. implanted GL261 cell-based orthotopic mouse model, the RasB8 transgenic astrocytoma mouse model, and a human GBM tissue microarray. We demonstrate that Tregs in brain tumors are predominantly thymus derived, since thymectomy, prior to i.c. GL261 cell implantation, significantly decreased the level of Tregs in mice with brain tumors. Accordingly, most Tregs in human GBM and mouse brain tumors expressed the nTreg transcription factor, Helios. Interestingly, a significant effect of the brain tumor microenvironment on Treg lineage programming was observed, based on higher levels of brain tumor-resident Tregs expressing glucocorticoid-induced tumor necrosis factor receptor and CD103 and lower levels of Tregs expressing CD62L and CD45RB compared with peripheral Tregs. Furthermore, there was a higher level of nTregs in brain tumors that expressed the proliferative marker Ki67 compared with iTregs and conventional CD4+ T cells. Our study demonstrates that future Treg-depleting therapies should aim to selectively target systemic rather than intratumoral nTregs in brain tumor-specific immunotherapeutic strategies. PMID:21908444

  15. Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors.

    PubMed

    Wainwright, Derek A; Sengupta, Sadhak; Han, Yu; Lesniak, Maciej S

    2011-12-01

    Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an average survival time of 15 months. Previously, we and others demonstrated that CD4(+)FoxP3(+) regulatory T cells (Tregs) infiltrate human GBM as well as mouse models that recapitulate malignant brain tumors. However, whether brain tumor-resident Tregs are thymus-derived natural Tregs (nTregs) or induced Tregs (iTregs), by the conversion of conventional CD4(+) T cells, has not been established. To investigate this question, we utilized the i.c. implanted GL261 cell-based orthotopic mouse model, the RasB8 transgenic astrocytoma mouse model, and a human GBM tissue microarray. We demonstrate that Tregs in brain tumors are predominantly thymus derived, since thymectomy, prior to i.c. GL261 cell implantation, significantly decreased the level of Tregs in mice with brain tumors. Accordingly, most Tregs in human GBM and mouse brain tumors expressed the nTreg transcription factor, Helios. Interestingly, a significant effect of the brain tumor microenvironment on Treg lineage programming was observed, based on higher levels of brain tumor-resident Tregs expressing glucocorticoid-induced tumor necrosis factor receptor and CD103 and lower levels of Tregs expressing CD62L and CD45RB compared with peripheral Tregs. Furthermore, there was a higher level of nTregs in brain tumors that expressed the proliferative marker Ki67 compared with iTregs and conventional CD4(+) T cells. Our study demonstrates that future Treg-depleting therapies should aim to selectively target systemic rather than intratumoral nTregs in brain tumor-specific immunotherapeutic strategies. PMID:21908444

  16. Nonlinear microscopy, infrared, and Raman microspectroscopy for brain tumor analysis

    NASA Astrophysics Data System (ADS)

    Meyer, Tobias; Bergner, Norbert; Bielecki, Christiane; Krafft, Christoph; Akimov, Denis; Romeike, Bernd F. M.; Reichart, Rupert; Kalff, Rolf; Dietzek, Benjamin; Popp, Jürgen

    2011-02-01

    Contemporary brain tumor research focuses on two challenges: First, tumor typing and grading by analyzing excised tissue is of utmost importance for choosing a therapy. Second, for prognostication the tumor has to be removed as completely as possible. Nowadays, histopathology of excised tissue using haematoxylin-eosine staining is the gold standard for the definitive diagnosis of surgical pathology specimens. However, it is neither applicable in vivo, nor does it allow for precise tumor typing in those cases when only nonrepresentative specimens are procured. Infrared and Raman spectroscopy allow for very precise cancer analysis due to their molecular specificity, while nonlinear microscopy is a suitable tool for rapid imaging of large tissue sections. Here, unstained samples from the brain of a domestic pig have been investigated by a multimodal nonlinear imaging approach combining coherent anti-Stokes Raman scattering, second harmonic generation, and two photon excited fluorescence microscopy. Furthermore, a brain tumor specimen was additionally analyzed by linear Raman and Fourier transform infrared imaging for a detailed assessment of the tissue types that is required for classification and to validate the multimodal imaging approach. Hence label-free vibrational microspectroscopic imaging is a promising tool for fast and precise in vivo diagnostics of brain tumors.

  17. Method for localizing heating in tumor tissue

    DOEpatents

    Doss, James D.; McCabe, Charles W.

    1977-04-12

    A method for a localized tissue heating of tumors is disclosed. Localized radio frequency current fields are produced with specific electrode configurations. Several electrode configurations are disclosed, enabling variations in electrical and thermal properties of tissues to be exploited.

  18. Emerging Insights into Barriers to Effective Brain Tumor Therapeutics

    PubMed Central

    Woodworth, Graeme F.; Dunn, Gavin P.; Nance, Elizabeth A.; Hanes, Justin; Brem, Henry

    2014-01-01

    There is great promise that ongoing advances in the delivery of therapeutics to the central nervous system (CNS) combined with rapidly expanding knowledge of brain tumor patho-biology will provide new, more effective therapies. Brain tumors that form from brain cells, as opposed to those that come from other parts of the body, rarely metastasize outside of the CNS. Instead, the tumor cells invade deep into the brain itself, causing disruption in brain circuits, blood vessel and blood flow changes, and tissue swelling. Patients with the most common and deadly form, glioblastoma (GBM) rarely live more than 2 years even with the most aggressive treatments and often with devastating neurological consequences. Current treatments include maximal safe surgical removal or biopsy followed by radiation and chemotherapy to address the residual tumor mass and invading tumor cells. However, delivering effective and sustained treatments to these invading cells without damaging healthy brain tissue is a major challenge and focus of the emerging fields of nanomedicine and viral and cell-based therapies. New treatment strategies, particularly those directed against the invasive component of this devastating CNS disease, are sorely needed. In this review, we (1) discuss the history and evolution of treatments for GBM, (2) define and explore three critical barriers to improving therapeutic delivery to invasive brain tumors, specifically, the neuro-vascular unit as it relates to the blood brain barrier, the extra-cellular space in regard to the brain penetration barrier, and the tumor genetic heterogeneity and instability in association with the treatment efficacy barrier, and (3) identify promising new therapeutic delivery approaches that have the potential to address these barriers and create sustained, meaningful efficacy against GBM. PMID:25101239

  19. Intra-operative brain tumor detection using elastic light single-scattering spectroscopy: a feasibility study

    NASA Astrophysics Data System (ADS)

    Canpolat, Murat; Akyüz, Mahmut; Gökhan, Güzide Ayşe; Gürer, Elif Inanç; Tuncer, Recai

    2009-09-01

    We have investigated the potential application of elastic light single-scattering spectroscopy (ELSSS) as an adjunctive tool for intraoperative rapid detection of brain tumors and demarcation of the tumor from the surrounding normal tissue. Measurements were performed on 29 excised tumor specimens from 29 patients. There were 21 instances of low-grade tumors and eight instances of high-grade tumors. Normal gray matter and white matter brain tissue specimens of four epilepsy patients were used as a control group. One low-grade and one high-grade tumor were misclassified as normal brain tissue. Of the low- and high-grade tumors, 20 out of 21 and 7 out of 8 were correctly classified by the ELSSS system, respectively. One normal white matter tissue margin was detected in a high-grade tumor, and three normal tissue margins were detected in three low-grade tumors using spectroscopic data analysis and confirmed by histopathology. The spectral slopes were shown to be positive for normal white matter brain tissue and negative for normal gray matter and tumor tissues. Our results indicate that signs of spectral slopes may enable the discrimination of brain tumors from surrounding normal white matter brain tissue with a sensitivity of 93% and specificity of 100%.

  20. Radiosensitized treatment of malignant brain tumors

    NASA Astrophysics Data System (ADS)

    Bloznelyte-Plesniene, Laima

    2003-12-01

    Around 12,000 deaths from glioblastoma occurs within the European Community annually. At present, the best available treatment for malignant brain tumors results in a median survival of patients of 15 months despite surgery, radiotherapy, and chemotherapy. The purpose of this paper is to review our results of radiosensitized treatment of malignant brain tumors.

  1. Glial brain tumor detection by using symmetry analysis

    NASA Astrophysics Data System (ADS)

    Pedoia, Valentina; Binaghi, Elisabetta; Balbi, Sergio; De Benedictis, Alessandro; Monti, Emanuele; Minotto, Renzo

    2012-02-01

    In this work a fully automatic algorithm to detect brain tumors by using symmetry analysis is proposed. In recent years a great effort of the research in field of medical imaging was focused on brain tumors segmentation. The quantitative analysis of MRI brain tumor allows to obtain useful key indicators of disease progression. The complex problem of segmenting tumor in MRI can be successfully addressed by considering modular and multi-step approaches mimicking the human visual inspection process. The tumor detection is often an essential preliminary phase to solvethe segmentation problem successfully. In visual analysis of the MRI, the first step of the experts cognitive process, is the detection of an anomaly respect the normal tissue, whatever its nature. An healthy brain has a strong sagittal symmetry, that is weakened by the presence of tumor. The comparison between the healthy and ill hemisphere, considering that tumors are generally not symmetrically placed in both hemispheres, was used to detect the anomaly. A clustering method based on energy minimization through Graph-Cut is applied on the volume computed as a difference between the left hemisphere and the right hemisphere mirrored across the symmetry plane. Differential analysis involves the loss the knowledge of the tumor side. Through an histogram analysis the ill hemisphere is recognized. Many experiments are performed to assess the performance of the detection strategy on MRI volumes in presence of tumors varied in terms of shapes positions and intensity levels. The experiments showed good results also in complex situations.

  2. Multiple Subsets of Brain Tumor Initiating Cells Coexist in Glioblastoma.

    PubMed

    Rennert, Robert C; Achrol, Achal S; Januszyk, Michael; Kahn, Suzana A; Liu, Tiffany T; Liu, Yi; Sahoo, Debashis; Rodrigues, Melanie; Maan, Zeshaan N; Wong, Victor W; Cheshier, Samuel H; Chang, Steven D; Steinberg, Gary K; Harsh, Griffith R; Gurtner, Geoffrey C

    2016-06-01

    Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs coexisting in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to divergent bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. Stem Cells 2016;34:1702-1707. PMID:26991945

  3. Clinical applications of choline PET/CT in brain tumors.

    PubMed

    Giovannini, Elisabetta; Lazzeri, Patrizia; Milano, Amalia; Gaeta, Maria Chiara; Ciarmiello, Andrea

    2015-01-01

    Malignant gliomas and metastatic tumors are the most common forms of brain tumors. From a clinical perspective, neuroimaging plays a significant role, in diagnosis, treatment planning, and follow-up. To date MRI is considered the current clinical gold standard for imaging, however, despite providing superior structural detail it features poor specificity in identifying viable tumors in brain treated with surgery, radiation, or chemotherapy. In the last years functional neuroimaging has become largely widespread thanks to the use of molecular tracers employed in cellular metabolism which has significantly improved the management of patients with brain tumors, especially in the post-treatment phase. Despite the considerable progress of molecular imaging in oncology its use in the diagnosis of brain tumors is still limited by a few wellknown technical problems. Because 18F-FDG, the most common radiotracer used in oncology, is avidly accumulated by normal cortex, the low tumor/background signal ratio makes it difficult to distinguish the tumor from normal surrounding tissues. By contrast, radiotracers with higher specificity for the tumor are labeled with a short half-life isotopes which restricts their use to those centers equipped with a cyclotron and radiopharmacy facility. 11C-choline has been reported as a suitable tracer for neuroimaging application. The recent availability of choline labeled with a long half-life radioisotope as 18F increases the possibility of studying this tracer's potential role in the staging of brain tumors. The present review focuses on the possible clinical applications of PET/CT with choline tracers in malignant brain tumors and brain metastases, with a special focus on malignant gliomas. PMID:25225894

  4. How Are Brain and Spinal Cord Tumors in Children Diagnosed?

    MedlinePlus

    ... spinal cord tumors in children staged? How are brain and spinal cord tumors diagnosed in children? Brain ... resonance angiography (MRA) or computerized tomographic angiography (CTA). Brain or spinal cord tumor biopsy Imaging tests such ...

  5. The impact of dietary isoflavonoids on malignant brain tumors.

    PubMed

    Sehm, Tina; Fan, Zheng; Weiss, Ruth; Schwarz, Marc; Engelhorn, Tobias; Hore, Nirjhar; Doerfler, Arnd; Buchfelder, Michael; Eyüpoglu, Iiker Y; Savaskan, Nic E

    2014-08-01

    Poor prognosis and limited therapeutic options render malignant brain tumors one of the most devastating diseases in clinical medicine. Current treatment strategies attempt to expand the therapeutic repertoire through the use of multimodal treatment regimens. It is here that dietary fibers have been recently recognized as a supportive natural therapy in augmenting the body's response to tumor growth. Here, we investigated the impact of isoflavonoids on primary brain tumor cells. First, we treated glioma cell lines and primary astrocytes with various isoflavonoids and phytoestrogens. Cell viability in a dose-dependent manner was measured for biochanin A (BCA), genistein (GST), and secoisolariciresinol diglucoside (SDG). Dose-response action for the different isoflavonoids showed that BCA is highly effective on glioma cells and nontoxic for normal differentiated brain tissues. We further investigated BCA in ex vivo and in vivo experimentations. Organotypic brain slice cultures were performed and treated with BCA. For in vivo experiments, BCA was intraperitoneal injected in tumor-implanted Fisher rats. Tumor size and edema were measured and quantified by magnetic resonance imaging (MRI) scans. In vascular organotypic glioma brain slice cultures (VOGIM) we found that BCA operates antiangiogenic and neuroprotective. In vivo MRI scans demonstrated that administered BCA as a monotherapy was effective in reducing significantly tumor-induced brain edema and showed a trend for prolonged survival. Our results revealed that dietary isoflavonoids, in particular BCA, execute toxicity toward glioma cells, antiangiogenic, and coevally neuroprotective properties, and therefore augment the range of state-of-the-art multimodal treatment approach. PMID:24898306

  6. Pericyte Antigens in Perivascular Soft Tissue Tumors

    PubMed Central

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Asatrian, Greg; Mravic, Marco; Soo, Chia; Ting, Kang; Dry, Sarah M.; Peault, Bruno; James, Aaron W.

    2015-01-01

    Introduction Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear line of differentiation, although most are presumed to originate from pericytes or modified perivascular cells. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor (previously termed hemangiopericytoma) was once hypothesized to have pericytic differentiation. Methods Here, we systematically examine pericyte immunohistochemical markers among glomus tumor (including malignant glomus tumor), myopericytoma, angioleiomyoma, and solitary fibrous tumor. Immunohistochemical staining and semiquantification was performed using well-defined pericyte antigens, including αSMA, CD146, and PDGFRβ. Results Glomus tumor and myopericytoma demonstrate diffuse staining for all pericyte markers, including immunohistochemical reactivity for αSMA, CD146, and PDGFRβ. Malignant glomus tumors all showed some degree of pericyte marker immunoreactivity, although it was significantly reduced. Angioleiomyoma shared a similar αSMA + CD146 + PDGFRβ+ immunophenotype; however, this was predominantly seen in the areas of perivascular tumor growth. Solitary fibrous tumors showed patchy PDGFRβ immunoreactivity only. Discussion In summary, pericyte marker expression is a ubiquitous finding in glomus tumor, myopericytoma, and angioleiomyoma. Malignant glomus tumor shows a comparative reduction in pericyte marker expression, which may represent partial loss of pericytic differentiation. Pericyte markers are essentially not seen in solitary fibrous tumor. The combination of αSMA, CD146, and PDGFRβ immunohistochemical stainings may be of utility for the evaluation of pericytic differentiation in soft tissue tumors. PMID:26085647

  7. Malignant metastatic carcinoid presenting as brain tumor

    PubMed Central

    Sundar, I. Vijay; Jain, S. K.; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  8. Malignant metastatic carcinoid presenting as brain tumor.

    PubMed

    Sundar, I Vijay; Jain, S K; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  9. Brain tumors at a nuclear facility.

    PubMed

    Reyes, M; Wilkinson, G S; Tietjen, G; Voelz, G L; Acquavella, J F; Bistline, R

    1984-10-01

    In response to an observed excess risk of brain tumor deaths among workers at the Rocky Flats Nuclear Facility (Colorado), a case-control study of all (n = 16) primary brain tumor deaths occurring among white males employed during 1952 through 1977 was conducted to investigate their relationship with occupational radiation/nonradiation exposures. For each case, four controls were individually matched on year of birth and period of employment. Although limited by a small number of cases, our study showed no statistically significant association between brain tumor death and exposure to internally deposited plutonium, external radiation, or other occupational risk factors. PMID:6491777

  10. Research of the multimodal brain-tumor segmentation algorithm

    NASA Astrophysics Data System (ADS)

    Lu, Yisu; Chen, Wufan

    2015-12-01

    It is well-known that the number of clusters is one of the most important parameters for automatic segmentation. However, it is difficult to define owing to the high diversity in appearance of tumor tissue among different patients and the ambiguous boundaries of lesions. In this study, a nonparametric mixture of Dirichlet process (MDP) model is applied to segment the tumor images, and the MDP segmentation can be performed without the initialization of the number of clusters. A new nonparametric segmentation algorithm combined with anisotropic diffusion and a Markov random field (MRF) smooth constraint is proposed in this study. Besides the segmentation of single modal brain tumor images, we developed the algorithm to segment multimodal brain tumor images by the magnetic resonance (MR) multimodal features and obtain the active tumor and edema in the same time. The proposed algorithm is evaluated and compared with other approaches. The accuracy and computation time of our algorithm demonstrates very impressive performance.

  11. The role of integrins in primary and secondary brain tumors.

    PubMed

    Schittenhelm, Jens; Tabatabai, Ghazaleh; Sipos, Bence

    2016-10-01

    The tumor environment plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Integrins, a family of cell surface receptors, bridge the extracellular matrix to the intracellular cytoskeleton. Since their first characterization 25 years ago, a vast amount of work has been performed to understand the essential role of integrins in cell development, tissue organization, tumor growth, vessel development and their signaling mechanisms. Their potential as therapeutic targets in various types of cancer is intensively studied. In this review, we discuss the expression patterns and functional role of integrin in primary brain tumors and brain metastases, provide an overview of clinical data on integrin inhibition and their potential application in imaging and therapy of these tumors. PMID:27097828

  12. Intraoperative infrared imaging of brain tumors

    PubMed Central

    Gorbach, Alexander M.; Heiss, John D.; Kopylev, Leonid; Oldfield, Edward H.

    2014-01-01

    Object Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear. Methods An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis–astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy. In four cases a cerebral artery was temporarily occluded during the course of the surgery and infrared emissions from the cortex before and after occlusion were compared to establish the relationship of local temperature to regional blood flow. Discrete temperature gradients were associated with surgically verified lesions in all cases. Depending on the type of tumor, the cortex overlying the tumor was either colder or warmer than the surrounding cortex. Spatial reorganization of thermal gradients was observed after tumor resection. Temperature gradients of the cortex in patients with tumors exceeded those measured in the cortex of patients who underwent epilepsy surgery. Conclusions Brain tumors induce changes in cerebral blood flow (CBF) in the cortex, which can be made visible by performing infrared imaging during cranial surgery. A reduction in CBF beyond the tumor margin improves after removal of the lesion. PMID:15599965

  13. Implantable tissue isolation chambers for analyzing tumor dynamics in vivo.

    PubMed

    Gruionu, Gabriel; Bazou, Despina; Maimon, Nir; Onita-Lenco, Mara; Gruionu, Lucian G; Huang, Peigen; Munn, Lance L

    2016-05-21

    Recruitment of new blood vessels from the surrounding tissue is central to tumor progression and involves a fundamental transition of the normal, organized vasculature into a dense disarray of vessels that infiltrates the tumor. At present, studying the co-development of the tumor and recruited normal tissue is experimentally challenging because many of the important events occur rapidly and over short length scales in a dense three-dimensional space. To overcome these experimental limitations, we partially confined tumors within biocompatible and optically clear tissue isolation chambers (TICs) and implanted them in mice to create a system that is more amenable to microscopic analysis. Our goal was to integrate the tumor into a recruited host tissue - complete with vasculature - and demonstrate that the system recapitulates relevant features of the tumor microenvironment. We show that the TICs allow clear visualization of the cellular events associated with tumor growth and progression at the host-tumor interface including cell infiltration, matrix remodeling and angiogenesis. The tissue within the chamber is viable for more than a month, and the process is robust in both the skin and brain. Treatment with losartan, an angiotensin II receptor antagonist, decreased the collagen density and fiber length in the TIC, consistent with the known activity of this drug. We further show that collagen fibers display characteristic tumor signatures and play a central role in angiogenesis, guiding the migration of tethered endothelial sprouts. The methodology combines accessible methods of microfabrication with animal models and will enable more informative studies of the cellular mechanisms of tumor progression. PMID:27128791

  14. Brain Tumor Epidemiology Consortium Membership Information

    Cancer.gov

    BTEC welcomes new members interested in the development of multi-center, inter-disciplinary collaborations that will lead to a better understanding of the etiology, outcomes and prevention of all brain tumors.

  15. Brain Tumors - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Brain Tumors URL of this page: https://www.nlm.nih.gov/medlineplus/languages/braintumors.html Other topics A-Z A B ...

  16. Staging Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  17. Banking Brain Tumor Specimens Using a University Core Facility.

    PubMed

    Bregy, Amade; Papadimitriou, Kyriakos; Faber, David A; Shah, Ashish H; Gomez, Carmen R; Komotar, Ricardo J; Egea, Sophie C

    2015-08-01

    Within the past three decades, the significance of banking human cancer tissue for the advancement of cancer research has grown exponentially. The purpose of this article is to detail our experience in collecting brain tumor specimens in collaboration with the University of Miami/Sylvester Tissue Bank Core Facility (UM-TBCF), to ensure the availability of high-quality samples of central nervous system tumor tissue for research. Successful tissue collection begins with obtaining informed consent from patients following institutional IRB and federal HIPAA guidelines, and it needs a well-trained professional staff and continued maintenance of high ethical standards and record keeping. Since starting in 2011, we have successfully banked 225 brain tumor specimens for research. Thus far, the most common tumor histology identified among those specimens has been glioblastoma (22.1%), followed by meningioma (18.1%). The majority of patients were White, non-Hispanics accounting for 45.1% of the patient population; Hispanic/Latinos accounted for 23%, and Black/African Americans accounted for 14%, which represent the particular population of the State of Florida according to the 2010 census data. The most common tumors found in each subgroup were as follows: Black/African American, glioblastoma and meningioma; Hispanic, metastasis and glioblastoma; White, glioblastoma and meningioma. The UM-TBCF is a valuable repository, offering high-quality tumor samples from a unique patient population. PMID:26280502

  18. Metastasis Infiltration: An Investigation of the Postoperative Brain-Tumor Interface

    SciTech Connect

    Raore, Bethwel; Schniederjan, Matthew; Prabhu, Roshan; Brat, Daniel J.; Shu, Hui-Kuo; Olson, Jeffrey J.

    2011-11-15

    Purpose: This study aims to evaluate brain infiltration of metastatic tumor cells past the main tumor resection margin to assess the biological basis for the use of stereotactic radiosurgery treatment of the tumor resection cavity and visualized resection edge or clinical target volume. Methods and Materials: Resection margin tissue was obtained after gross total resection of a small group of metastatic lesions from a variety of primary sources. The tissue at the border of the tumor and brain tissue was carefully oriented and processed to evaluate the presence of tumor cells within brain tissue and their distance from the resection margin. Results: Microscopic assessment of the radially oriented tissue samples showed no tumor cells infiltrating the surrounding brain tissue. Among the positive findings were reactive astrocytosis observed on the brain tissue immediately adjacent to the tumor resection bed margin. Conclusions: The lack of evidence of metastatic tumor cell infiltration into surrounding brain suggests the need to target only a narrow depth of the resection cavity margin to minimize normal tissue injury and prevent treatment size-dependent stereotactic radiosurgery complications.

  19. Radiation treatment of brain tumors: Concepts and strategies

    SciTech Connect

    Marks, J.E. )

    1989-01-01

    Ionizing radiation has demonstrated clinical value for a multitude of CNS tumors. Application of the different physical modalities available has made it possible for the radiotherapist to concentrate the radiation in the region of the tumor with relative sparing of the surrounding normal tissues. Correlation of radiation dose with effect on cranial soft tissues, normal brain, and tumor has shown increasing effect with increasing dose. By using different physical modalities to alter the distribution of radiation dose, it is possible to increase the dose to the tumor and reduce the dose to the normal tissues. Alteration of the volume irradiated and the dose delivered to cranial soft tissues, normal brain, and tumor are strategies that have been effective in improving survival and decreasing complications. The quest for therapeutic gain using hyperbaric oxygen, neutrons, radiation sensitizers, chemotherapeutic agents, and BNCT has met with limited success. Both neoplastic and normal cells are affected simultaneously by all modalities of treatment, including ionizing radiation. Consequently, one is unable to totally depopulate a tumor without irreversibly damaging the normal tissues. In the case of radiation, it is the brain that limits delivery of curative doses, and in the case of chemical additives, it is other organ systems, such as bone marrow, liver, lung, kidneys, and peripheral nerves. Thus, the major obstacle in the treatment of malignant gliomas is our inability to preferentially affect the tumor with the modalities available. Until it is possible to directly target the neoplastic cell without affecting so many of the adjacent normal cells, the quest for therapeutic gain will go unrealized.72 references.

  20. The Role of Fast Cell Cycle Analysis in Pediatric Brain Tumors.

    PubMed

    Alexiou, George A; Vartholomatos, George; Stefanaki, Kalliopi; Lykoudis, Efstathios G; Patereli, Amalia; Tseka, Georgia; Tzoufi, Meropi; Sfakianos, George; Prodromou, Neofytos

    2015-01-01

    Cell cycle analysis by flow cytometry has not been adequately studied in pediatric brain tumors. We investigated the value of a modified rapid (within 6 min) cell cycle analysis protocol for the characterization of malignancy of pediatric brain tumors and for the differentiation of neoplastic from nonneoplastic tissue for possible intraoperative application. We retrospectively studied brain tumor specimens from patients treated at our institute over a 5-year period. All tumor samples were histopathologically verified before flow-cytometric analysis. The histopathological examination of permanent tissue sections was the gold standard. There were 68 brain tumor cases. All tumors had significantly lower G0/G1 and significantly higher S phase and mitosis fractions than normal brain tissue. Furthermore low-grade tumors could be differentiated from high-grade tumors. DNA aneuploidy was detected in 35 tumors. A correlation between S phase fraction and Ki-67 index was found in medulloblastomas and anaplastic ependymomas. Rapid cell cycle analysis by flow cytometry is a promising method for the identification of neoplastic tissue intraoperatively. Low-grade tumors could be differentiated from high-grade tumors. Thus, cell cycle analysis can be a valuable adjunct to the histopathological evaluation of pediatric brain tumors, whereas its intraoperative application warrants further investigation. PMID:26287721

  1. Multimodality stereotactic brain tissue identification: the NASA smart probe project

    NASA Technical Reports Server (NTRS)

    Andrews, R.; Mah, R.; Aghevli, A.; Freitas, K.; Galvagni, A.; Guerrero, M.; Papsin, R.; Reed, C.; Stassinopoulos, D.

    1999-01-01

    Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures. Copyright 2000 S. Karger AG, Basel.

  2. Embryonal brain tumors and developmental control genes

    SciTech Connect

    Aguzzi, A.

    1995-12-31

    Cell proliferation in embryogenesis and neoplastic transformation is thought to be controlled by similar sets of regulatory genes. This is certainly true for tumors of embryonic origin, such as Ewing sarcoma, Wilms` tumor and retinoblastoma, in which developmental control genes are either activated as oncogenes to promote proliferation, or are inactivated to eliminate their growth suppressing function. However, to date little is known about the genetic events underlying the pathogenesis of medulloblastoma, the most common brain tumor in children, which still carries an unfavourable prognosis. None of the common genetic alterations identified in other neuroectodermal tumors, such as mutation of the p53 gene or amplification of tyrosine kinase receptor genes, could be uncovered as key events in the formation of medulloblastoma. The identification of regulatory genes which are expressed in this pediatric brain tumor may provide an alternative approach to gain insight into the molecular aspects of tumor formation.

  3. Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy

    PubMed Central

    Ji, Minbiao; Lewis, Spencer; Camelo-Piragua, Sandra; Ramkissoon, Shakti H.; Snuderl, Matija; Venneti, Sriram; Fisher-Hubbard, Amanda; Garrard, Mia; Fu, Dan; Wang, Anthony C.; Heth, Jason A.; Maher, Cormac O.; Sanai, Nader; Johnson, Timothy D.; Freudiger, Christian W.; Sagher, Oren; Xie, Xiaoliang Sunney; Orringer, Daniel A.

    2016-01-01

    Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a non-destructive, label-free optical method, to reveal glioma infiltration in animal models. Here we show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ=0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density and protein:lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density and protein:lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Importantly, quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery. PMID:26468325

  4. Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.

    PubMed

    Ji, Minbiao; Lewis, Spencer; Camelo-Piragua, Sandra; Ramkissoon, Shakti H; Snuderl, Matija; Venneti, Sriram; Fisher-Hubbard, Amanda; Garrard, Mia; Fu, Dan; Wang, Anthony C; Heth, Jason A; Maher, Cormac O; Sanai, Nader; Johnson, Timothy D; Freudiger, Christian W; Sagher, Oren; Xie, Xiaoliang Sunney; Orringer, Daniel A

    2015-10-14

    Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models. We show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ = 0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density, and protein/lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density, and protein/lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery. PMID:26468325

  5. Soft tissue tumors of the sinonasal tract.

    PubMed

    Johncilla, Melanie; Jo, Vickie Y

    2016-03-01

    Primary soft tissue tumors arising in the sinonasal tract are rare. While many mesenchymal neoplasms have been reported in the nasal cavity, sinuses, and nasopharynx, few are distinctive to this anatomic region. Some tumor types are relatively more common in this area, such as schwannoma and rhabdomyosarcoma. Nasopharyngeal angiofibroma and sinonasal hemangiopericytoma are unique entities of the sinonasal tract, as well as the recently characterized biphenotypic sinonasal sarcoma. This review discusses the clinical, morphologic, and immunohistochemical features and currently known molecular data of the more frequently encountered soft tissue tumors of the sinonasal tract. PMID:26472693

  6. Infrared spectra of thyroid tumor tissues

    NASA Astrophysics Data System (ADS)

    Tolstorozhev, G. B.; Skornyakov, I. V.; Butra, V. A.

    2010-07-01

    We used infrared spectroscopy methods to study thyroid tumor tissues removed during surgery. The IR spectra of the surgical material are compared with data from histological examination. We show that in malignant neoplasms, the spectra of proteins in the region of C=O vibrations are different from the spectra of these substances in benign tumors and in tissues outside the pathological focus at a distance >1 cm from the margin of the tumor. The differences in the spectra are due to changes in the supermolecular structure of the proteins, resulting from rearrangement of the system of hydrogen bonds. We identify the spectral signs of malignant pathologies.

  7. Multiresolution texture models for brain tumor segmentation in MRI.

    PubMed

    Iftekharuddin, Khan M; Ahmed, Shaheen; Hossen, Jakir

    2011-01-01

    In this study we discuss different types of texture features such as Fractal Dimension (FD) and Multifractional Brownian Motion (mBm) for estimating random structures and varying appearance of brain tissues and tumors in magnetic resonance images (MRI). We use different selection techniques including KullBack - Leibler Divergence (KLD) for ranking different texture and intensity features. We then exploit graph cut, self organizing maps (SOM) and expectation maximization (EM) techniques to fuse selected features for brain tumors segmentation in multimodality T1, T2, and FLAIR MRI. We use different similarity metrics to evaluate quality and robustness of these selected features for tumor segmentation in MRI for real pediatric patients. We also demonstrate a non-patient-specific automated tumor prediction scheme by using improved AdaBoost classification based on these image features. PMID:22255946

  8. Increased IMP dehydrogenase gene expression in solid tumor tissues and tumor cell lines

    SciTech Connect

    Collart, F.R.; Chubb, C.B.; Mirkin, B.L.; Huberman, E.

    1992-07-10

    IMP dehydrogenase, a regulatory enzyme of guanine nucleotide biosynthesis, may play a role in cell proliferation and malignancy. To assess this possibility, we examined IMP dehydrogenase expression in a series of human solid tumor tissues and tumor cell lines in comparison with their normal counterparts. Increased IMP dehydrogenase gene expression was observed in brain tumors relative to normal brain tissue and in sarcoma cells relative to normal fibroblasts. Similarly, in several B- and T-lymphoid leukemia cell lines, elevated levels of IMP dehydrogenase mRNA and cellular enzyme were observed in comparison with the levels in peripheral blood lymphocytes. These results are consistent with an association between increased IMP dehydrogenase expression and either enhanced cell proliferation or malignant transformation.

  9. The biology of radiosurgery and its clinical applications for brain tumors

    PubMed Central

    Kondziolka, Douglas; Shin, Samuel M.; Brunswick, Andrew; Kim, Irene; Silverman, Joshua S.

    2015-01-01

    Stereotactic radiosurgery (SRS) was developed decades ago but only began to impact brain tumor care when it was coupled with high-resolution brain imaging techniques such as computed tomography and magnetic resonance imaging. The technique has played a key role in the management of virtually all forms of brain tumor. We reviewed the radiobiological principles of SRS on tissue and how they pertain to different brain tumor disorders. We reviewed the clinical outcomes on the most common indications. This review found that outcomes are well documented for safety and efficacy and show increasing long-term outcomes for benign tumors. Brain metastases SRS is common, and its clinical utility remains in evolution. The role of SRS in brain tumor care is established. Together with surgical resection, conventional radiotherapy, and medical therapies, patients have an expanding list of options for their care. Clinicians should be familiar with radiosurgical principles and expected outcomes that may pertain to different brain tumor scenarios. PMID:25267803

  10. General Information about Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... Cord Tumors Treatment Overview (PDQ®)–Patient Version General Information About Childhood Brain and Spinal Cord Tumors Go ... types of brain and spinal cord tumors. The information from tests and procedures done to detect (find) ...

  11. Proton MRS imaging in pediatric brain tumors.

    PubMed

    Zarifi, Maria; Tzika, A Aria

    2016-06-01

    Magnetic resonance (MR) techniques offer a noninvasive, non-irradiating yet sensitive approach to diagnosing and monitoring pediatric brain tumors. Proton MR spectroscopy (MRS), as an adjunct to MRI, is being more widely applied to monitor the metabolic aspects of brain cancer. In vivo MRS biomarkers represent a promising advance and may influence treatment choice at both initial diagnosis and follow-up, given the inherent difficulties of sequential biopsies to monitor therapeutic response. When combined with anatomical or other types of imaging, MRS provides unique information regarding biochemistry in inoperable brain tumors and can complement neuropathological data, guide biopsies and enhance insight into therapeutic options. The combination of noninvasively acquired prognostic information and the high-resolution anatomical imaging provided by conventional MRI is expected to surpass molecular analysis and DNA microarray gene profiling, both of which, although promising, depend on invasive biopsy. This review focuses on recent data in the field of MRS in children with brain tumors. PMID:27233788

  12. The proteomics of pediatric brain tumors.

    PubMed

    Anagnostopoulos, Athanasios K; Tsangaris, George T

    2014-10-01

    Pediatric tumors of the CNS are the leading cause of cancer-related mortality in children. In pediatric pathology, brain tumors constitute the most frequent solid malignancy. An unparalleled outburst of information in pediatric neuro-oncology research has been witnessed over the last few years, largely due to increased use of high-throughput technologies such as genomics, proteomics and meta-analysis tools. Input from these technologies gives scientists the advantage of early prognosis assessment, more accurate diagnosis and prospective curative intent in the pediatric brain tumor clinical setting. The present review aims to summarize current knowledge on research applying proteomics techniques or proteomics-based approaches performed on pediatric brain tumors. Proteins that can be used as potential disease markers or molecular targets, and their biological significance, are herein listed and discussed. Furthermore, future perspectives that proteomics technologies may offer regarding this devastating disorder are presented. PMID:25059388

  13. Visual analysis of longitudinal brain tumor perfusion

    NASA Astrophysics Data System (ADS)

    Glaßer, Sylvia; Oeltze, Steffen; Preim, Uta; Bjørnerud, Atle; Hauser, Helwig; Preim, Bernhard

    2013-02-01

    In clinical research on diagnosis and evaluation of brain tumors, longitudinal perfusion MRI studies are acquired for tumor grading as well as to monitor and assess treatment response and patient prognosis. Within this work, we demonstrate how visual analysis techniques can be adapted to multidimensional datasets from such studies within a framework to support the computer-aided diagnosis of brain tumors. Our solution builds on two innovations: First, we introduce a pipeline yielding comparative, co-registered quantitative perfusion parameter maps over all time steps of the longitudinal study. Second, based on these time-dependent parameter maps, visual analysis methods were developed and adapted to reveal valuable insight into tumor progression, especially regarding the clinical research area of low grade glioma transformation into high grade gliomas. Our examination of four longitudinal brain studies demonstrates the suitability of the presented visual analysis methods and comprises new possibilities for the clinical researcher to characterize the development of low grade gliomas.

  14. Enhanced Performance of Brain Tumor Classification via Tumor Region Augmentation and Partition

    PubMed Central

    Cheng, Jun; Huang, Wei; Cao, Shuangliang; Yang, Ru; Yang, Wei; Yun, Zhaoqiang; Wang, Zhijian; Feng, Qianjin

    2015-01-01

    Automatic classification of tissue types of region of interest (ROI) plays an important role in computer-aided diagnosis. In the current study, we focus on the classification of three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor) in T1-weighted contrast-enhanced MRI (CE-MRI) images. Spatial pyramid matching (SPM), which splits the image into increasingly fine rectangular subregions and computes histograms of local features from each subregion, exhibits excellent results for natural scene classification. However, this approach is not applicable for brain tumors, because of the great variations in tumor shape and size. In this paper, we propose a method to enhance the classification performance. First, the augmented tumor region via image dilation is used as the ROI instead of the original tumor region because tumor surrounding tissues can also offer important clues for tumor types. Second, the augmented tumor region is split into increasingly fine ring-form subregions. We evaluate the efficacy of the proposed method on a large dataset with three feature extraction methods, namely, intensity histogram, gray level co-occurrence matrix (GLCM), and bag-of-words (BoW) model. Compared with using tumor region as ROI, using augmented tumor region as ROI improves the accuracies to 82.31% from 71.39%, 84.75% from 78.18%, and 88.19% from 83.54% for intensity histogram, GLCM, and BoW model, respectively. In addition to region augmentation, ring-form partition can further improve the accuracies up to 87.54%, 89.72%, and 91.28%. These experimental results demonstrate that the proposed method is feasible and effective for the classification of brain tumors in T1-weighted CE-MRI. PMID:26447861

  15. Application of SLT contact laser in resection of brain tumors

    NASA Astrophysics Data System (ADS)

    Li, Han-Jie; Li, Zhi-Qiang; Li, Chan-Yuan

    1998-11-01

    28 cases of brain tumors were operated by SLT contact Nd:YAG laser from October 1995 to May 1997 in our hospital. Among these, 14 are menin-giomas, 5 are astrocytomas. Others are tumors such as acoustic neuromas, craniopharyngiomas, etc 21 cases underwent common craniotomy, 3, laser endoscopy operation; and 4, laser therapy under microscopy. Method of tumor resection: firstly, cutting and separating the tumor from brain tissues with GRP by 5-15w; secondly, vaporizing parenchyma of tumor with MTRL and sucking it, again, cutting and separating and so on, lastly removing the tumor entirely. The power of vaporization for glioma or tumors in ventricles is about 20-30w, but for meningiomas, 30-60w. MT was used on power of 15-20w to coagulate and homeostate the left cavity of tumor. According to our experience, laser operation can make bleeding reduced markedly, tumor resection become more thorough, and postoperative response and complications decrease obviously.

  16. Tumor

    MedlinePlus

    ... be removed because of their location or harmful effect on the surrounding normal brain tissue. If a tumor is cancer , possible treatments may include: Chemotherapy Radiation Surgery Targeted cancer therapy Biologic therapy Other treatment options

  17. Recent developments in brain tumor predisposing syndromes.

    PubMed

    Johansson, Gunnar; Andersson, Ulrika; Melin, Beatrice

    2016-01-01

    The etiologies of brain tumors are in the most cases unknown, but improvements in genetics and DNA screening have helped to identify a wide range of brain tumor predisposition disorders. In this review we are discussing some of the most common predisposition disorders, namely: neurofibromatosis type 1 and 2, schwannomatosis, rhabdoid tumor predisposition disorder, nevoid basal cell carcinoma syndrome (Gorlin), tuberous sclerosis complex, von Hippel-Lindau, Li-Fraumeni and Turcot syndromes. Recent findings from the GLIOGENE collaboration and the newly identified glioma causing gene POT1, will also be discussed. Genetics. We will describe these disorders from a genetic and clinical standpoint, focusing on the difference in clinical symptoms depending on the underlying gene or germline mutation. Central nervous system (CNS) tumors. Most of these disorders predispose the carriers to a wide range of symptoms. Herein, we will focus particularly on tumors affecting the CNS and discuss improvements of targeted therapy for the particular disorders. PMID:26634384

  18. Validation techniques for quantitative brain tumors measurements.

    PubMed

    Salman, Y; Assal, M; Badawi, A; Alian, S; -M El-Bayome, M

    2005-01-01

    Quantitative measurements of tumor volume becomes more realistic with the use of imaging- particularly specially when the tumor have non-ellipsoidal morphology, which remains subtle, irregular and difficult to assess by visual metric and clinical examination. The quantitative measurements depend strongly on the accuracy of the segmentation technique. The validity of brain tumor segmentation methods is an important issue in medical imaging because it has a direct impact on many applications such as surgical planning and quantitative measurements of tumor volume. Our goal was to examine two popular segmentation techniques seeded region growing and active contour "snakes" to be compared against experts' manual segmentations as the gold standard. We illustrated these methods on brain tumor volume cases using MR imaging modality. PMID:17281898

  19. A noninvasive multimodal technique to monitor brain tumor vascularization

    NASA Astrophysics Data System (ADS)

    Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E.

    2007-09-01

    Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.

  20. Contrast medium accumulation and washout in canine brain tumors and irradiated normal brain: a CT study of kinetics

    SciTech Connect

    Fike, J.R.; Cann, C.E.

    1984-04-01

    Kinetics of an iodinated contrast medium were evaluated quantitatively as a function of time up to one hour after intravenous infusion in the brains of dogs with experimentally induced radiation damage and dogs with spontaneous brain tumor. Radiation damage was characterized by an increase in iodine accumulation soon after the infusion, while tumor concentration of iodine either showed no change or decreased with time. These results suggest that contrast kinetic studies may be useful in differentiating radiation damage to normal brain tissue from a malignant brain tumor.

  1. Metabolic brain imaging correlated with clinical features of brain tumors

    SciTech Connect

    Alavi, J.; Alavi, A.; Dann, R.; Kushner, M.; Chawluk, J.; Powlis, W.; Reivich, M.

    1985-05-01

    Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1 enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.

  2. Training stem cells for treatment of malignant brain tumors

    PubMed Central

    Li, Shengwen Calvin; Kabeer, Mustafa H; Vu, Long T; Keschrumrus, Vic; Yin, Hong Zhen; Dethlefs, Brent A; Zhong, Jiang F; Weiss, John H; Loudon, William G

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system. PMID:25258664

  3. Psychiatric aspects of brain tumors: A review

    PubMed Central

    Madhusoodanan, Subramoniam; Ting, Mark Bryan; Farah, Tara; Ugur, Umran

    2015-01-01

    Infrequently, psychiatric symptoms may be the only manifestation of brain tumors. They may present with mood symptoms, psychosis, memory problems, personality changes, anxiety, or anorexia. Symptoms may be misleading, complicating the clinical picture. A comprehensive review of the literature was conducted regarding reports of brain tumors and psychiatric symptoms from 1956-2014. Search engines used include PubMed, Ovid, Psych Info, MEDLINE, and MedScape. Search terms included psychiatric manifestations/symptoms, brain tumors/neoplasms. Our literature search yielded case reports, case studies, and case series. There are no double blind studies except for post-diagnosis/-surgery studies. Early diagnosis is critical for improved quality of life. Symptoms that suggest work-up with neuroimaging include: new-onset psychosis, mood/memory symptoms, occurrence of new or atypical symptoms, personality changes, and anorexia without body dysmorphic symptoms. This article reviews the existing literature regarding the diagnosis and management of this clinically complex condition. PMID:26425442

  4. Confronting pediatric brain tumors: parent stories.

    PubMed

    McMillan, Gigi

    2014-01-01

    This narrative symposium brings to light the extreme difficulties faced by parents of children diagnosed with brain tumors. NIB editorial staff and narrative symposium editors, Gigi McMillan and Christy A. Rentmeester, developed a call for stories that was distributed on several list serves and posted on Narrative Inquiry in Bioethics' website. The call asks parents to share their personal experience of diagnosis, treatment, long-term effects of treatment, social issues and the doctor-patient-parent dynamic that develops during this process. Thirteen stories are found in the print version of the journal and an additional six supplemental stories are published online only through Project MUSE. One change readers may notice is that the story authors are not listed in alphabetical order. The symposium editors had a vision for this issue that included leading readers through the timeline of this topic: diagnosis-treatment-acute recovery-recurrence-treatment (again)-acute recovery (again)-long-term quality of life-(possibly) end of life. Stories are arranged to help lead the reader through this timeline.Gigi McMillan is a patient and research subject advocate, co-founder of We Can, Pediatric Brain Tumor Network, as well as, the mother of a child who suffered from a pediatric brain tumor. She also authored the introduction for this symposium. Christy Rentmeester is an Associate Professor of Health Policy and Ethics in the Creighton University School of Medicine. She served as a commentator for this issue. Other commentators for this issue are Michael Barraza, a clinical psychologist and board member of We Can, Pediatric Brain Tumor Network; Lisa Stern, a pediatrician who has diagnosed six children with brain tumors in her 20 years of practice; and Katie Rose, a pediatric brain tumor patient who shares her special insights about this world. PMID:24748242

  5. Development and characterization of a brain tumor mimicking fluorescence phantom

    NASA Astrophysics Data System (ADS)

    Haj-Hosseini, Neda; Kistler, Benjamin; Wârdell, Karin

    2014-03-01

    Fluorescence guidance using 5-aminolevulinic acid (5-ALA) for brain tumor resection is a recent technique applied to the highly malignant brain tumors. Five-ALA accumulates as protoporphyrin IX fluorophore in the tumor cells in different concentrations depending on the tumor environment and cell properties. Our group has developed a fluorescence spectroscopy system used with a hand-held probe intra-operatively. The system has shown improvement of fluorescence detection and allows quantification that preliminarily correlates with tumor malignancy grade during surgery. However, quantification of fluorescence is affected by several factors including the initial fluorophore concentration, photobleaching due to operating lamps and attenuation from the blood. Accordingly, an optical phantom was developed to enable controlled fluorescence measurements and evaluation of the system outside of the surgical procedure. The phantom mimicked the optical properties of glioma at the specific fluorescence excitation wavelength when different concentrations of the fluorophore were included in the phantom. To allow evaluation of photobleaching, kinetics of fluorophore molecules in the phantom was restricted by solidifying the phantoms. Moreover, a model for tissue autofluorescence was added. The fluorescence intensity's correlation with fluorophore concentration in addition to the photobleaching properties were investigated in the phantoms and were compared to the clinical data measured on the brain tumor.

  6. Organization of brain tissue - Is the brain a noisy processor.

    NASA Technical Reports Server (NTRS)

    Adey, W. R.

    1972-01-01

    This paper presents some thoughts on functional organization in cerebral tissue. 'Spontaneous' wave and unit firing are considered as essential phenomena in the handling of information. Various models are discussed which have been suggested to describe the pseudorandom behavior of brain cells, leading to a view of the brain as an information processor and its role in learning, memory, remembering and forgetting.

  7. Biphasic modeling of brain tumor biomechanics and response to radiation treatment

    PubMed Central

    Angeli, Stelios; Stylianopoulos, Triantafyllos

    2016-01-01

    Biomechanical forces are central in tumor progression and response to treatment. This becomes more important in brain cancers where tumors are surrounded by tissues with different mechanical properties. Existing mathematical models ignore direct mechanical interactions of the tumor with the normal brain. Here, we developed a clinically relevant model, which predicts tumor growth accounting directly for mechanical interactions. A three-dimensional model of the gray and white matter and the cerebrospinal fluid was constructed from magnetic resonance images of a normal brain. Subsequently, a biphasic tissue growth theory for an initial tumor seed was employed, incorporating the effects of radiotherapy. Additionally, three different sets of brain tissue properties taken from the literature were used to investigate their effect on tumor growth. Results show the evolution of solid stress and interstitial fluid pressure within the tumor and the normal brain. Heterogeneous distribution of the solid stress exerted on the tumor resulted in a 35 % spatial variation in cancer cell proliferation. Interestingly, the model predicted that distant from the tumor, normal tissues still undergo significant deformations while it was found that intratumoral fluid pressure is elevated. Our predictions relate to clinical symptoms of brain cancers and present useful tools for therapy planning. PMID:27086116

  8. Biphasic modeling of brain tumor biomechanics and response to radiation treatment.

    PubMed

    Angeli, Stelios; Stylianopoulos, Triantafyllos

    2016-06-14

    Biomechanical forces are central in tumor progression and response to treatment. This becomes more important in brain cancers where tumors are surrounded by tissues with different mechanical properties. Existing mathematical models ignore direct mechanical interactions of the tumor with the normal brain. Here, we developed a clinically relevant model, which predicts tumor growth accounting directly for mechanical interactions. A three-dimensional model of the gray and white matter and the cerebrospinal fluid was constructed from magnetic resonance images of a normal brain. Subsequently, a biphasic tissue growth theory for an initial tumor seed was employed, incorporating the effects of radiotherapy. Additionally, three different sets of brain tissue properties taken from the literature were used to investigate their effect on tumor growth. Results show the evolution of solid stress and interstitial fluid pressure within the tumor and the normal brain. Heterogeneous distribution of the solid stress exerted on the tumor resulted in a 35% spatial variation in cancer cell proliferation. Interestingly, the model predicted that distant from the tumor, normal tissues still undergo significant deformations while it was found that intratumoral fluid pressure is elevated. Our predictions relate to clinical symptoms of brain cancers and present useful tools for therapy planning. PMID:27086116

  9. Brain tumors and synchrotron radiation: Methodological developments in quantitative brain perfusion imaging and radiation therapy

    SciTech Connect

    Adam, Jean-Francois

    2005-04-01

    High-grade gliomas are the most frequent type of primary brain tumors in adults. Unfortunately, the management of glioblastomas is still mainly palliative and remains a difficult challenge, despite advances in brain tumor molecular biology and in some emerging therapies. Synchrotron radiation opens fields for medical imaging and radiation therapy by using monochromatic intense x-ray beams. It is now well known that angiogenesis plays a critical role in the tumor growth process and that brain perfusion is representative of the tumor mitotic activity. Synchrotron radiation quantitative computed tomography (SRCT) is one of the most accurate techniques for measuring in vivo contrast agent concentration and thus computing precise and accurate absolute values of the brain perfusion key parameters. The methodological developments of SRCT absolute brain perfusion measurements as well as their preclinical validation are detailed in this thesis. In particular, absolute cerebral volume and blood brain barrier permeability high-resolution (pixel size <50x50 {mu}m{sup 2}) parametric maps were reported. In conventional radiotherapy, the treatment of these tumors remains a delicate challenge, because the damages to the surrounding normal brain tissue limit the amount of radiation that can be delivered. One strategy to overcome this limitation is to infuse an iodinated contrast agent to the patient during the irradiation. The contrast agent accumulates in the tumor, through the broken blood brain barrier, and the irradiation is performed with kilovoltage x rays, in tomography mode, the tumor being located at the center of rotation and the beam size adjusted to the tumor dimensions. The dose enhancement results from the photoelectric effect on the heavy element and from the irradiation geometry. Synchrotron beams, providing high intensity, tunable monochromatic x rays, are ideal for this treatment. The beam properties allow the selection of monochromatic irradiation, at the optimal

  10. [Chemotherapy for brain tumors in adult patients].

    PubMed

    Weller, M

    2008-02-01

    Chemotherapy has become a third major treatment option for patients with brain tumors, in addition to surgery and radiotherapy. The role of chemotherapy in the treatment of gliomas is no longer limited to recurrent disease. Temozolomide has become the standard of care in newly diagnosed glioblastoma. Several ongoing trials seek to define the role of chemotherapy in the primary care of other gliomas. Some of these studies are no longer only based on histological diagnoses, but take into consideration molecular markers such as MGMT promoter methylation and loss of genetic material on chromosomal arms 1p and 19q. Outside such clinical trials chemotherapy is used in addition to radiotherapy, e.g., in anaplastic astrocytoma, medulloblastoma or germ cell tumors, or as an alternative to radiotherapy, e.g., in anaplastic oligodendroglial tumors or low-grade gliomas. In contrast, there is no established role for chemotherapy in other tumors such as ependymomas, meningiomas or neurinomas. Primary cerebral lymphomas are probably the only brain tumors which can be cured by chemotherapy alone and only by chemotherapy. The chemotherapy of brain metastases follows the recommendations for the respective primary tumors. Further, strategies of combined radiochemotherapy using mainly temozolomide or topotecan are currently explored. Leptomeningeal metastases are treated by radiotherapy or systemic or intrathecal chemotherapy depending on their pattern of growth. PMID:18253773

  11. Connective tissue growth factor in tumor pathogenesis

    PubMed Central

    2012-01-01

    Key roles for connective tissue growth factor (CTGF/CCN2) are demonstrated in the wound repair process where it promotes myofibroblast differentiation and angiogenesis. Similar mechanisms are active in tumor-reactive stroma where CTGF is expressed. Other potential roles include prevention of hypoxia-induced apoptosis and promoting epithelial-mesenchymal transistion (EMT). CTGF expression in tumors has been associated to both tumor suppression and progression. For example, CTGF expression in acute lymphoblastic leukemia, breast, pancreas and gastric cancer correlates to worse prognosis whereas the opposite is true for colorectal, lung and ovarian cancer. This discrepancy is not yet understood. High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon. These tumors maintain a high grade of differentiation and low proliferation. Despite this, they are malignant and most patients have metastatic disease at diagnosis. These tumors demonstrate several phenotypes potentially related to CTGF function namely: cell migration, absent tumor cell apoptosis, as well as, reactive and well vascularised myofibroblast rich stroma and fibrosis development locally and in distal organs. The presence of CTGF in other endocrine tumors indicates a role in the progression of well-differentiated tumors. PMID:23259759

  12. Optical spectroscopy for stereotactic biopsy of brain tumors

    NASA Astrophysics Data System (ADS)

    Markwardt, Niklas; von Berg, Anna; Fiedler, Sebastian; Goetz, Marcus; Haj-Hosseini, Neda; Polzer, Christoph; Stepp, Herbert; Zelenkov, Petr; Rühm, Adrian

    2015-07-01

    Stereotactic biopsy procedure is performed to obtain a tissue sample for diagnosis purposes. Currently, a fiber-based mechano-optical device for stereotactic biopsies of brain tumors is developed. Two different fluorophores are employed to improve the safety and reliability of this procedure: The fluorescence of intravenously applied indocyanine green (ICG) facilitates the recognition of blood vessels and thus helps minimize the risk of cerebral hemorrhages. 5- aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence is used to localize vital tumor tissue. ICG fluorescence detection using a 2-fiber probe turned out to be an applicable method to recognize blood vessels about 1.5 mm ahead of the fiber tip during a brain tumor biopsy. Moreover, the suitability of two different PpIX excitation wavelengths regarding practical aspects was investigated: While PpIX excitation in the violet region (at 405 nm) allows for higher sensitivity, red excitation (at 633 nm) is noticeably superior with regard to blood layers obscuring the fluorescence signal. Contact measurements on brain simulating agar phantoms demonstrated that a typical blood coverage of the tumor reduces the PpIX signal to about 75% and nearly 0% for 633 nm and 405 nm excitation, respectively. As a result, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of high-grade gliomas in stereotactic biopsy.

  13. Molecular Genetics of Pediatric Soft Tissue Tumors

    PubMed Central

    Chang, Chung-Che; Shidham, Vinod B.

    2003-01-01

    The application of molecular genetics to pediatric soft tissue tumors has grown tremendously over the last decade. It has resulted in the identification of novel genes that have provided us with an increased understanding of oncogenesis. Furthermore, these findings have identified diagnostic and potentially prognostic factors for patient management. Molecular diagnostic techniques, such as reverse transcription PCR (RT-PCR) and fluorescence in situ hybridization (FISH), have become important tools for evaluating pediatric soft tissue tumors. By detecting characteristic fusion genes, these techniques have greatly increased the diagnostic accuracy of histopathological classification. One of the exciting promises of the development of these molecular techniques is their ability to detect micrometastasis and minimal residual disease. Monitoring of minimal residual disease in pediatric soft tissue tumors by quantitative RT-PCR may provide important prognostic information. Furthermore, the potential development of targeted therapy based on the understanding of the molecular pathology of a specific soft tissue tumor may complement existing treatments and improve disease outcome. PMID:12876204

  14. Malignant soft tissue tumors in children.

    PubMed

    Thacker, Mihir M

    2013-10-01

    Soft tissue masses are frequently seen in children. Although most are benign or reactive, soft tissue sarcomas (STS)-both rhabdomyosarcoma (most common) and non-rhabdo STS, do occur in the extremities. Appropriate evaluation of extremity soft tissue tumors often includes a biopsy as the clinical and imaging features may not be enough to establish a definitive diagnosis. Much needs to be done for improving the treatment of these rare but often devastating sarcomas. Given the small numbers of these cases seen at various centers, collaborative efforts should be made to further our understanding and improve the management of these challenging cases. PMID:24095080

  15. Development of multifunctional nanoparticles for brain tumor diagnosis and therapy

    NASA Astrophysics Data System (ADS)

    Veiseh, Omid

    Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents developed for magnetic resonance (MR) imaging and drug delivery. MNPs have traditionally been developed for disease imaging via passive targeting, but recent advances in nanotechnology have enabled cellular-specific targeting, drug delivery and multi-modal imaging using these nanoparticles. Opportunities now exist to engineer MNP with designated features (e.g., size, coatings, and molecular functionalizations) for specific biomedical applications. The goal of this interdisciplinary research project is to develop targeting multifunctional nanoparticles, serving as both contrast agents and drug carriers that can effectively pass biological barriers, for diagnosis, staging and treatment of brain tumors. The developed nanoparticle system consists of a superparamagnetic iron oxide nanoparticle core (NP) and a shell comprised of biodegradable polymers such as polyethylene glycol (PEG) and chitosan. Additionally, near-infrared fluorescing (NIRF) molecules were integrated onto the NP shell to enable optical detection. Tumor targeting was achieved by the addition of chlorotoxin, a peptide with that has high affinity to 74 out of the 79 classifications of primary brain tumors and ability to illicit a therapeutic effect. This novel NP system was tested both in vitro and in vivo and was shown to specifically target gliomas in tissue culture and medulloblastomas in transgenic mice with an intact blood brain barriers (BBB), and delineate tumor boundaries in both MR and optical imaging. Additionally, the therapeutic potential of this NP system was explored in vitro, which revealed a unique nanoparticle-enabled pathway that enhances the therapeutic potential of bound peptides by promoting the internalization of membrane bound cell surface receptors. This NP system was further modified with siRNA and evaluated as a carrier for brain tumor targeted gene therapy. Most significantly, the evaluation of

  16. [Soft tissue sarcomas and gastrointestinal stromal tumors].

    PubMed

    Reichardt, P

    2016-03-01

    Soft tissue sarcomas are rare tumors that represent a major challenge due to varying clinical presentations and often interdisciplinary treatment concepts. Gold standard for the treatment of localized resectable soft tissue sarcomas is complete surgical removal. In metastatic soft tissue sarcoma, systemic therapy is the treatment of choice. The most active drugs are anthracyclines and ifosfamide. Combination chemotherapy has improved both response rate and progression-free survival at the cost of increased toxicity. Imatinib at a dose of 400 mg/day is the gold standard for patients with advanced or metastatic gastrointestinal stromal tumors (GIST). In patients with a mutation in KIT exon 9, 800 mg/day is the recommended dose. In imatinib refractory or intolerant patients, sunitinib is recommended. Regorafenib has been approved for third-line therapy. PMID:26907871

  17. Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors.

    PubMed

    Eberlin, Livia S; Norton, Isaiah; Orringer, Daniel; Dunn, Ian F; Liu, Xiaohui; Ide, Jennifer L; Jarmusch, Alan K; Ligon, Keith L; Jolesz, Ferenc A; Golby, Alexandra J; Santagata, Sandro; Agar, Nathalie Y R; Cooks, R Graham

    2013-01-29

    The main goal of brain tumor surgery is to maximize tumor resection while preserving brain function. However, existing imaging and surgical techniques do not offer the molecular information needed to delineate tumor boundaries. We have developed a system to rapidly analyze and classify brain tumors based on lipid information acquired by desorption electrospray ionization mass spectrometry (DESI-MS). In this study, a classifier was built to discriminate gliomas and meningiomas based on 36 glioma and 19 meningioma samples. The classifier was tested and results were validated for intraoperative use by analyzing and diagnosing tissue sections from 32 surgical specimens obtained from five research subjects who underwent brain tumor resection. The samples analyzed included oligodendroglioma, astrocytoma, and meningioma tumors of different histological grades and tumor cell concentrations. The molecular diagnosis derived from mass-spectrometry imaging corresponded to histopathology diagnosis with very few exceptions. Our work demonstrates that DESI-MS technology has the potential to identify the histology type of brain tumors. It provides information on glioma grade and, most importantly, may help define tumor margins by measuring the tumor cell concentration in a specimen. Results for stereotactically registered samples were correlated to preoperative MRI through neuronavigation, and visualized over segmented 3D MRI tumor volume reconstruction. Our findings demonstrate the potential of ambient mass spectrometry to guide brain tumor surgery by providing rapid diagnosis, and tumor margin assessment in near-real time. PMID:23300285

  18. Brain tumors: Special characters for research and banking

    PubMed Central

    Kheirollahi, Majid; Dashti, Sepideh; Khalaj, Zahra; Nazemroaia, Fatemeh; Mahzouni, Parvin

    2015-01-01

    A brain tumor is an intracranial neoplasm within the brain or in the central spinal canal. Primary malignant brain tumors affect about 200,000 people worldwide every year. Brain cells have special characters. Due to the specific properties of brain tumors, including epidemiology, growth, and division, investigation of brain tumors and the interpretation of results is not simple. Research to identify the genetic alterations of human tumors improves our knowledge of tumor biology, genetic interactions, progression, and preclinical therapeutic assessment. Obtaining data for prevention, diagnosis, and therapy requires sufficient samples, and brain tumors have a wide range. As a result, establishing the bank of brain tumors is very important and essential. PMID:25625110

  19. Ion transporters in brain tumors

    PubMed Central

    Cong, Damin; Zhu, Wen; Kuo, John S.; Hu, Shaoshan; Sun, Dandan

    2015-01-01

    Ion transporters are important in regulation of ionic homeostasis, cell volume, and cellular signal transduction under physiological conditions. They have recently emerged as important players in cancer progression. In this review, we discussed two important ion transporter proteins, sodium-potassium-chloride cotransporter isoform 1 (NKCC-1) and sodium-hydrogen exchanger isoform 1 (NHE-1) in Glioblastoma multiforme (GBM) and other malignant tumors. NKCC-1 is a Na+-dependent Cl− transporter that mediates the movement of Na+, K+, and Cl− ions across the plasma membrane and maintains cell volume and intracellular K+ and Cl− homeostasis. NHE-1 is a ubiquitously expressed cell membrane protein which regulates intracellular pH (pHi) and extracellular microdomain pH (pHe) homeostasis and cell volume. Here, we summarized recent pre-clinical experimental studies on NKCC-1 and NHE-1 in GBM and other malignant tumors, such as breast cancer, hepatocellular carcinoma, and lung cancer. These studies illustrated that pharmacological inhibition or down-regulation of these ion transporter proteins reduces proliferation, increases apoptosis, and suppresses migration and invasion of cancer cells. These new findings reveal the potentials of these ion transporters as new targets for cancer diagnosis and/or treatment. PMID:25620102

  20. The kynurenine pathway in brain tumor pathogenesis.

    PubMed

    Adams, Seray; Braidy, Nady; Bessede, Alban; Bessesde, Alban; Brew, Bruce J; Grant, Ross; Teo, Charlie; Guillemin, Gilles J

    2012-11-15

    Brain tumors are among the most common and most chemoresistant tumors. Despite treatment with aggressive treatment strategies, the prognosis for patients harboring malignant gliomas remains dismal. The kynurenine pathway (KP) is the principal route of L-tryptophan catabolism leading to the formation of the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD(+)), and important neuroactive metabolites, including the neurotoxin, quinolinic acid (QUIN), the neuroprotective agent, picolinic acid (PIC), the T(H)17/Treg balance modulator, 3-hydroxyanthranilic acid (3-HAA), and the immunosuppressive agent, L-kynurenine (KYN). This review provides a new perspective on KP dysregulation in defeating antitumor immune responses, specifically bringing light to the lower segment of the KP, particularly QUIN-induced neurotoxicity and downregulation of the enzyme α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) as a potential mechanism of tumor progression. Given its immunosuppressive effects, 3-HAA produced from the KP may also play a role in suppressing antitumor immunity in human tumors. The enzyme indoleamine 2, 3-dioxygenase (IDO-1) initiates and regulates the first step of the KP in most cells. Mounting evidence directly implicates that the induction and overexpression of IDO-1 in various tumors is a crucial mechanism facilitating tumor immune evasion and persistence. Tryptophan 2, 3-dioxygenase (TDO-2), which initiates the same first step of the KP as IDO-1, has likewise recently been shown to be a mechanism of tumoral immune resistance. Further, it was also recently shown that TDO-2-dependent production of KYN by brain tumors might be a novel mechanism for suppressing antitumor immunity and supporting tumor growth through the activation of the Aryl hydrocarbon receptor (AhR). This newly identified TDO-2-KYN-AhR signaling pathway opens up exciting future research opportunities and may represent a novel therapeutic target in cancer therapy

  1. YKL-40 protein in osteosarcoma tumor tissue.

    PubMed

    Thorn, Andrea Pohly; Daugaard, Søren; Christensen, Lise Hanne; Christensen, Ib Jarle; Petersen, Michael Mørk

    2016-06-01

    YKL-40, a cellular glycoprotein isolated from the human osteosarcoma (OS) cell line MG63, is increased in the blood of patients with various types of cancer, and is found as an independent prognostic variable for survival. YKL-40 is also present with variable intensity in the tumor cells of some cancer types, but survival results have been conflicting. The aim of this study was to investigate the tissue expression of YKL-40 and its possible role as a predictive marker in patients with OS. Forty-eight patients were included in the study. Diagnostic biopsies were analyzed by immunohistochemistry; YKL-staining scores as well as CD14 and CD163 scores were determined, and survival data were determined statistically. A universal intense immunostaining for YKL-40 was found in all tumor cells, but tumor cell/stroma ratio varied, and this ratio (%) served as staining score. Using 24% as mean score to divide the material, patients with tumors of high YKL-40 score had a better survival than patients with low score (p = 0.05). YKL-positive macrophages had no influence on the result. Unexpectedly and contrary to some other findings in cancer tissues, this study has shown a correlation between high YKL-40 tumor cell/matrix ratio and longer overall survival in OS. PMID:26988273

  2. Simulation of brain tumor resection in image-guided neurosurgery

    NASA Astrophysics Data System (ADS)

    Fan, Xiaoyao; Ji, Songbai; Fontaine, Kathryn; Hartov, Alex; Roberts, David; Paulsen, Keith

    2011-03-01

    Preoperative magnetic resonance images are typically used for neuronavigation in image-guided neurosurgery. However, intraoperative brain deformation (e.g., as a result of gravitation, loss of cerebrospinal fluid, retraction, resection, etc.) significantly degrades the accuracy in image guidance, and must be compensated for in order to maintain sufficient accuracy for navigation. Biomechanical finite element models are effective techniques that assimilate intraoperative data and compute whole-brain deformation from which to generate model-updated MR images (uMR) to improve accuracy in intraoperative guidance. To date, most studies have focused on early surgical stages (i.e., after craniotomy and durotomy), whereas simulation of more complex events at later surgical stages has remained to be a challenge using biomechanical models. We have developed a method to simulate partial or complete tumor resection that incorporates intraoperative volumetric ultrasound (US) and stereovision (SV), and the resulting whole-brain deformation was used to generate uMR. The 3D ultrasound and stereovision systems are complimentary to each other because they capture features deeper in the brain beneath the craniotomy and at the exposed cortical surface, respectively. In this paper, we illustrate the application of the proposed method to simulate brain tumor resection at three temporally distinct surgical stages throughout a clinical surgery case using sparse displacement data obtained from both the US and SV systems. We demonstrate that our technique is feasible to produce uMR that agrees well with intraoperative US and SV images after dural opening, after partial tumor resection, and after complete tumor resection. Currently, the computational cost to simulate tumor resection can be up to 30 min because of the need for re-meshing and the trial-and-error approach to refine the amount of tissue resection. However, this approach introduces minimal interruption to the surgical workflow

  3. Sunitinib impedes brain tumor progression and reduces tumor-induced neurodegeneration in the microenvironment

    PubMed Central

    Hatipoglu, Gökçe; Hock, Stefan W; Weiss, Ruth; Fan, Zheng; Sehm, Tina; Ghoochani, Ali; Buchfelder, Michael; Savaskan, Nicolai E; Eyüpoglu, Ilker Y

    2015-01-01

    Malignant gliomas can be counted to the most devastating tumors in humans. Novel therapies do not achieve significant prolonged survival rates. The cancer cells have an impact on the surrounding vital tissue and form tumor zones, which make up the tumor microenvironment. We investigated the effects of sunitinib, a small molecule multitargeted receptor tyrosine kinase inhibitor, on constituents of the tumor microenvironment such as gliomas, astrocytes, endothelial cells, and neurons. Sunitinib has a known anti-angiogenic effect. We found that sunitinib normalizes the aberrant tumor-derived vasculature and reduces tumor vessel pathologies (i.e. auto-loops). Sunitinib has only minor effects on the normal, physiological, non-proliferating vasculature. We found that neurons and astrocytes are protected by sunitinib against glutamate-induced cell death, whereas sunitinib acts as a toxin towards proliferating endothelial cells and tumor vessels. Moreover, sunitinib is effective in inducing glioma cell death. We determined the underlying pathways by which sunitinib operates as a toxin on gliomas and found vascular endothelial growth factor receptor 2 (VEGFR2, KDR/Flk1) as the main target to execute gliomatoxicity. The apoptosis-inducing effect of sunitinib can be mimicked by inhibition of VEGFR2. Knockdown of VEGFR2 can, in part, foster the resistance of glioma cells to receptor tyrosine kinase inhibitors. Furthermore, sunitinib alleviates tumor-induced neurodegeneration. Hence, we tested whether temozolomide treatment could be potentiated by sunitinib application. Here we show that sunitinib can amplify the effects of temozolomide in glioma cells. Thus, our data indicate that combined treatment with temozolomide does not abrogate the effects of sunitinib. In conclusion, we found that sunitinib acts as a gliomatoxic agent and at the same time carries out neuroprotective effects, reducing tumor-induced neurodegeneration. Thus, this report uncovered sunitinib's actions on

  4. Segmentation of liver region with tumorous tissues

    NASA Astrophysics Data System (ADS)

    Zhang, Xuejun; Lee, Gobert; Tajima, Tetsuji; Kitagawa, Teruhiko; Kanematsu, Masayuki; Zhou, Xiangrong; Hara, Takeshi; Fujita, Hiroshi; Yokoyama, Ryujiro; Kondo, Hiroshi; Hoshi, Hiroaki; Nawano, Shigeru; Shinozaki, Kenji

    2007-03-01

    Segmentation of an abnormal liver region based on CT or MR images is a crucial step in surgical planning. However, precisely carrying out this step remains a challenge due to either connectivities of the liver to other organs or the shape, internal texture, and homogeneity of liver that maybe extensively affected in case of liver diseases. Here, we propose a non-density based method for extracting the liver region containing tumor tissues by edge detection processing. False extracted regions are eliminated by a shape analysis method and thresholding processing. If the multi-phased images are available then the overall outcome of segmentation can be improved by subtracting two phase images, and the connectivities can be further eliminated by referring to the intensity on another phase image. Within an edge liver map, tumor candidates are identified by their different gray values relative to the liver. After elimination of the small and nonspherical over-extracted regions, the final liver region integrates the tumor region with the liver tissue. In our experiment, 40 cases of MDCT images were used and the result showed that our fully automatic method for the segmentation of liver region is effective and robust despite the presence of hepatic tumors within the liver.

  5. Automatic brain tumor detection in MRI: methodology and statistical validation

    NASA Astrophysics Data System (ADS)

    Iftekharuddin, Khan M.; Islam, Mohammad A.; Shaik, Jahangheer; Parra, Carlos; Ogg, Robert

    2005-04-01

    Automated brain tumor segmentation and detection are immensely important in medical diagnostics because it provides information associated to anatomical structures as well as potential abnormal tissue necessary to delineate appropriate surgical planning. In this work, we propose a novel automated brain tumor segmentation technique based on multiresolution texture information that combines fractal Brownian motion (fBm) and wavelet multiresolution analysis. Our wavelet-fractal technique combines the excellent multiresolution localization property of wavelets to texture extraction of fractal. We prove the efficacy of our technique by successfully segmenting pediatric brain MR images (MRIs) from St. Jude Children"s Research Hospital. We use self-organizing map (SOM) as our clustering tool wherein we exploit both pixel intensity and multiresolution texture features to obtain segmented tumor. Our test results show that our technique successfully segments abnormal brain tissues in a set of T1 images. In the next step, we design a classifier using Feed-Forward (FF) neural network to statistically validate the presence of tumor in MRI using both the multiresolution texture and the pixel intensity features. We estimate the corresponding receiver operating curve (ROC) based on the findings of true positive fractions and false positive fractions estimated from our classifier at different threshold values. An ROC, which can be considered as a gold standard to prove the competence of a classifier, is obtained to ascertain the sensitivity and specificity of our classifier. We observe that at threshold 0.4 we achieve true positive value of 1.0 (100%) sacrificing only 0.16 (16%) false positive value for the set of 50 T1 MRI analyzed in this experiment.

  6. Mapping of language brain areas in patients with brain tumors.

    PubMed

    Hyder, Rasha; Kamel, Nidal; Boon, Tang Tong; Reza, Faruque

    2015-08-01

    Language cortex in the human brain shows high variability among normal individuals and may exhibit a considerable shift from its original position due to tumor growth. Mapping the precise location of language areas is important before surgery to avoid postoperative language deficits. In this paper, the Magnetoencephalography (MEG) recording and the MRI scanning of six brain tumorous subjects are used to localize the language specific areas. MEG recordings were performed during two silent reading tasks; silent word reading and silent picture naming. MEG source imaging is performed using distributed source modeling technique called CLARA ("Classical LORETA Analysis Recursively Applied"). Estimated MEG sources are overlaid on individual MRI of each patient to improve interpretation of MEG source imaging results. The results show successful identification of the essential language areas and clear definition of the time course of neural activation connecting them. PMID:26736340

  7. Towards the use of HIFU, in Conjunction with Surgery, in the Treatment of Malignant Brain Tumors

    NASA Astrophysics Data System (ADS)

    Dahl, Elizabeth; Nguyen, Lisa T.; Sparks, Rachel E.; Brayman, Andy A.; Olios, Ryan J.; Silbergeld, Daniel L.; Vaezy, Sarah; Mourad, Pierre D.

    2006-05-01

    The first medical response to the presence of a brain tumor is often its resection, both to alleviate mass effect, and to obtain tissue for diagnosis, itself necessary for guiding adjunctive therapy. Malignant brain tumors typically recur at the tumor resection margin. Most current chemotherapy and radiotherapy strategies target local recurrence with limited success. Here we review a new strategy for delivering chemotherapeutics for brain tumor recurrence. It uses intra-operative high-intensity focused ultrasound (HIFU) to transiently open the blood-brain barrier (BBB) over a significantly large volume of brain at and near the resection margin to enhance the subsequent delivery of systemically delivered chemotherapeutic agents into the region of tumor recurrence.

  8. Home care for brain tumor patients

    PubMed Central

    Pace, Andrea; Villani, Veronica; Di Pasquale, Antonella; Benincasa, Dario; Guariglia, Lara; Ieraci, Sonia; Focarelli, Silvia; Carapella, Carmine Maria; Pompili, Alfredo

    2014-01-01

    Background Brain tumor patients are quite different from other populations of cancer patients due to the complexity of supportive care needs, the trajectory of disease, the very short life expectancy, and resulting need for a specific palliative approach. Methods A pilot program of comprehensive palliative care for brain tumor patients was started in the Regina Elena National Cancer Institute of Rome in October 2000, supported by the Lazio Regional Health System. The aim of this model of assistance was to meet patient's needs for care in all stages of disease, support the families, and reduce the rehospitalization rate. The efficacy of the model of care was evaluated analyzing the place of death, caregiver satisfaction, rehospitalization rate, and the impact on costs to the health system. Results From October 2000 to December 2012, 848 patients affected by brain tumor were enrolled in a comprehensive program of neuro-oncological home care. Out of 529 patients who died, 323 (61%) were assisted at home until death, 117 (22.2%) died in hospital, and 89 (16.8%) died in hospice. A cost-effectiveness analysis demonstrated a significant reduction in hospital readmission rates in the last 2 months of life compared with the control group (16.7% vs 38%; P < .001). Conclusions Our findings concerning death at home, rehospitalization rate, quality of life, and satisfaction of patients and their relatives with the care received suggest that a neuro-oncologic palliative home-care program has a positive impact on the quality of care for brain tumor patients, particularly at the end of life. PMID:26034609

  9. Distribution of hematoporphyrin derivative in the rat 9l gliosarcoma brain tumor analyzed by digital video fluorescence microscopy.

    PubMed

    Boggan, J E; Walter, R; Edwards, M S; Borcich, J K; Davis, R L; Koonce, M; Berns, M W

    1984-12-01

    A digital video fluorescence microscopy technique was used to evaluate the distribution of hematoporphyrin derivative (HPD) in the rat intracerebral 9L gliosarcoma brain-tumor model at 4, 24, 48, and 72 hours after intravenous administration of 10 mg/kg of the drug. Compared to surrounding normal brain, there was significant preferential uptake of HPD into the tumor. In sections surveyed, fluorescence reached a maximum value by 24 hours; however, only 33% to 44% of the tumor was fluorescent. In contrast, fluorescence within the surrounding normal brain was maximum at 4 hours, but was present in less than 1% of the brain tissue evaluated. The effect of HPD sensitization to a laser light dose (633 nm) of 30 joules/sq cm delivered through the intact skull was evaluated histologically in 10 rats. A patchy coagulation necrosis, possibly corresponding to the distribution of HPD fluorescence seen within the tumor, was observed. There was evidence that photoradiation therapy (PRT) affects defective tumor vasculature and that a direct tumor cell toxicity spared normal brain tissue. Despite these findings, limited uptake of HPD in tumor and the brain adjacent to tumor may decrease the effectiveness of PRT in the 9L gliosarcoma brain-tumor model. Because of the similarity between the capillary system of the 9L tumor and human brain tumors, PRT may have a limited therapeutic effect in patients with malignant brain tumors. PMID:6239014

  10. Finite element modeling of haptic thermography: A novel approach for brain tumor detection during minimally invasive neurosurgery.

    PubMed

    Sadeghi-Goughari, Moslem; Mojra, Afsaneh

    2015-10-01

    Intraoperative Thermal Imaging (ITI) is a novel neuroimaging method that can potentially locate tissue abnormalities and hence improves surgeon's diagnostic ability. In the present study, thermography technique coupled with artificial tactile sensing method called "haptic thermography" is utilized to investigate the presence of an abnormal object as a tumor with an elevated temperature relative to the normal tissue in the brain. The brain tissue is characterized as a hyper-viscoelastic material to be descriptive of mechanical behavior of the brain tissue during tactile palpation. Based on a finite element approach, Magnetic Resonance Imaging (MRI) data of a patient diagnosed to have a brain tumor is utilized to simulate and analyze the capability of haptic thermography in detection and localization of brain tumor. Steady-state thermal results prove that temperature distribution is an appropriate outcome of haptic thermography for the superficial tumors while heat flux distribution can be used as an extra thermal result for deeply located tumors. PMID:26590456

  11. Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

    SciTech Connect

    Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

    2012-03-01

    Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results: The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.

  12. New therapeutic approach for brain tumors: Intranasal delivery of telomerase inhibitor GRN163

    PubMed Central

    Hashizume, Rintaro; Ozawa, Tomoko; Gryaznov, Sergei M.; Bollen, Andrew W.; Lamborn, Kathleen R.; Frey, William H.; Deen, Dennis F.

    2008-01-01

    The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are greatly needed for brain-tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain and could provide an alternative to intravenous injection and convection-enhanced delivery. We treated rats bearing intracerebral human tumor xeno-grafts intranasally with GRN163, an oligonucleotide N3′→P5′thio-phosphoramidate telomerase inhibitor. 3′-Fuorescein isothiocyanate (FITC)–labeled GRN163 was administered intranasally every 2 min as 6 μl drops into alternating sides of the nasal cavity over 22 min. FITC-labeled GRN163 was present in tumor cells at all time points studied, and accumulation of GRN163 peaked at 4 h after delivery. Moreover, GRN163 delivered intranasally, daily for 12 days, significantly prolonged the median survival from 35 days in the control group to 75.5 days in the GRN163-treated group. Thus, intranasal delivery of GRN163 readily bypassed the blood-brain barrier, exhibited favorable tumor uptake, and inhibited tumor growth, leading to a prolonged lifespan for treated rats compared to controls. This delivery approach appears to kill tumor cells selectively, and no toxic effects were noted in normal brain tissue. These data support further development of intranasal delivery of tumor-specific therapeutic agents for brain tumor patients. PMID:18287341

  13. New therapeutic approach for brain tumors: Intranasal delivery of telomerase inhibitor GRN163.

    PubMed

    Hashizume, Rintaro; Ozawa, Tomoko; Gryaznov, Sergei M; Bollen, Andrew W; Lamborn, Kathleen R; Frey, William H; Deen, Dennis F

    2008-04-01

    The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are greatly needed for brain-tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain and could provide an alternative to intravenous injection and convection-enhanced delivery. We treated rats bearing intracerebral human tumor xenografts intranasally with GRN163, an oligonucleotide N3'-->P5'thio-phosphoramidate telomerase inhibitor. 3'-Fuorescein isothiocyanate (FITC)-labeled GRN163 was administered intranasally every 2 min as 6 microl drops into alternating sides of the nasal cavity over 22 min. FITC-labeled GRN163 was present in tumor cells at all time points studied, and accumulation of GRN163 peaked at 4 h after delivery. Moreover, GRN163 delivered intranasally, daily for 12 days, significantly prolonged the median survival from 35 days in the control group to 75.5 days in the GRN163-treated group. Thus, intranasal delivery of GRN163 readily bypassed the blood-brain barrier, exhibited favorable tumor uptake, and inhibited tumor growth, leading to a prolonged lifespan for treated rats compared to controls. This delivery approach appears to kill tumor cells selectively, and no toxic effects were noted in normal brain tissue. These data support further development of intranasal delivery of tumor-specific therapeutic agents for brain tumor patients. PMID:18287341

  14. Acellular organ scaffolds for tumor tissue engineering

    NASA Astrophysics Data System (ADS)

    Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

    2015-12-01

    Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

  15. Improving the accuracy of brain tumor surgery via Raman-based technology.

    PubMed

    Hollon, Todd; Lewis, Spencer; Freudiger, Christian W; Sunney Xie, X; Orringer, Daniel A

    2016-03-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors. PMID:26926067

  16. Improving the accuracy of brain tumor surgery via Raman-based technology

    PubMed Central

    Hollon, Todd; Lewis, Spencer; Freudiger, Christian W.; Xie, X. Sunney; Orringer, Daniel A.

    2016-01-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors. PMID:26926067

  17. Brain Tumor Database, a free relational database for collection and analysis of brain tumor patient information.

    PubMed

    Bergamino, Maurizio; Hamilton, David J; Castelletti, Lara; Barletta, Laura; Castellan, Lucio

    2015-03-01

    In this study, we describe the development and utilization of a relational database designed to manage the clinical and radiological data of patients with brain tumors. The Brain Tumor Database was implemented using MySQL v.5.0, while the graphical user interface was created using PHP and HTML, thus making it easily accessible through a web browser. This web-based approach allows for multiple institutions to potentially access the database. The BT Database can record brain tumor patient information (e.g. clinical features, anatomical attributes, and radiological characteristics) and be used for clinical and research purposes. Analytic tools to automatically generate statistics and different plots are provided. The BT Database is a free and powerful user-friendly tool with a wide range of possible clinical and research applications in neurology and neurosurgery. The BT Database graphical user interface source code and manual are freely available at http://tumorsdatabase.altervista.org. PMID:25784642

  18. Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link?

    PubMed Central

    Germano, Isabelle; Swiss, Victoria; Casaccia, Patrizia

    2010-01-01

    The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of BTSC and discuss the similarities between the characteristics of these cells and those of the endogenous population of neural stem cells (NPCs) residing in germinal areas of the adult brain. Finally, we propose possible mechanisms of cancer initiation and progression and suggest a model of tumor initiation that includes intrinsic changes of resident NSC and potential changes in the microenvironment defining the niche where the NSC reside. PMID:20045420

  19. Adenoviral virotherapy for malignant brain tumors

    PubMed Central

    Nandi, Suvobroto; Lesniak, Maciej S

    2009-01-01

    Glioblastoma multiforme (GBM) is the most common form of primary brain cancer. In the past decade, virotherapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have an advantage over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. However, the lack of coxsackie and adenovirus receptors (CAR) on surface of gliomas provides for inefficient transduction of wild-type adenoviral vectors in these tumors. By targeting receptors that are over-expressed in gliomas, modified adenoviral constructs have been shown to efficiently infect glioma cells. In addition, by taking advantage of tumor specific promoter (TSP) elements, oncolytic adenoviral vectors offer the promise of selective tumor-specific replication. This dual targeting strategy has enabled specificity in both laboratory and pre-clinical settings. This review looks at current trends in adenoviral virotherapy of gliomas, with an emphasis on targeting modalities and future clinical applications. PMID:19456208

  20. Adenoviral virotherapy for malignant brain tumors.

    PubMed

    Nandi, Suvobroto; Lesniak, Maciej S

    2009-06-01

    Glioblastoma multiforme is the most common form of primary brain cancer. In the past decade, virotherapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have an advantage over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. However, the lack of coxsackie and adenovirus receptors on surface of gliomas provides for inefficient transduction of wild-type adenoviral vectors in these tumors. By targeting receptors that are overexpressed in gliomas, modified adenoviral constructs have been shown to efficiently infect glioma cells. In addition, by taking advantage of tumor-specific promoter elements, oncolytic adenoviral vectors offer the promise of selective tumor-specific replication. This dual targeting strategy has enabled specificity in both laboratory and pre-clinical settings. This review examines current trends in adenoviral virotherapy of gliomas, with an emphasis on targeting modalities and future clinical applications. PMID:19456208

  1. Computer applications to radioactive-seed: Brain-tumor implants

    SciTech Connect

    Meli, J.A.; Dicker, C.S.; Schulz, R.J.

    1989-05-01

    Malignant brain tumors, in general, and anaplastic astrocytoma and glioblastoma multiforme in particular, have been highly refractory to conventional treatments including surgery, chemotherapy and external-beam irradiation. Although better local control can be achieved with high-dose, external beam irradiation, necrosis of normal brain tissue reduces the quality of life and survival. In order to localize the radiation dose given to brain tumors, the temporary implantation of /sup 125/I and /sup 192/Ir seeds is undergoing clinical trials at several medical centers. Computers play a key role in this treatment modality: in addition to being essential for image reconstruction of CT scans, a computer is used to reconstruct a tumor volume from outlined regions on individual cuts; a programable calculator is used in conjunction with a stereotaxic head holder to obtain the coordinates of the radioactive seeds; a radiation-therapy, treatment-planning computer is used to optimize the radioactive-seed positions and strengths, and to generate the corresponding dose distribution.

  2. Raman molecular imaging of brain frozen tissue sections.

    PubMed

    Kast, Rachel E; Auner, Gregory W; Rosenblum, Mark L; Mikkelsen, Tom; Yurgelevic, Sally M; Raghunathan, Aditya; Poisson, Laila M; Kalkanis, Steven N

    2014-10-01

    Raman spectroscopy provides a molecular signature of the region being studied. It is ideal for neurosurgical applications because it is non-destructive, label-free, not impacted by water concentration, and can map an entire region of tissue. The objective of this paper is to demonstrate the meaningful spatial molecular information provided by Raman spectroscopy for identification of regions of normal brain, necrosis, diffusely infiltrating glioma and solid glioblastoma (GBM). Five frozen section tissues (1 normal, 1 necrotic, 1 GBM, and 2 infiltrating glioma) were mapped in their entirety using a 300-µm-square step size. Smaller regions of interest were also mapped using a 25-µm step size. The relative concentrations of relevant biomolecules were mapped across all tissues and compared with adjacent hematoxylin and eosin-stained sections, allowing identification of normal, GBM, and necrotic regions. Raman peaks and peak ratios mapped included 1003, 1313, 1431, 1585, and 1659 cm(-1). Tissue maps identified boundaries of grey and white matter, necrosis, GBM, and infiltrating tumor. Complementary information, including relative concentration of lipids, protein, nucleic acid, and hemoglobin, was presented in a manner which can be easily adapted for in vivo tissue mapping. Raman spectroscopy can successfully provide label-free imaging of tissue characteristics with high accuracy. It can be translated to a surgical or laboratory tool for rapid, non-destructive imaging of tumor margins. PMID:25038847

  3. Adaptive Localization of Focus Point Regions via Random Patch Probabilistic Density from Whole-Slide, Ki-67-Stained Brain Tumor Tissue

    PubMed Central

    Alomari, Yazan M.; MdZin, Reena Rahayu

    2015-01-01

    Analysis of whole-slide tissue for digital pathology images has been clinically approved to provide a second opinion to pathologists. Localization of focus points from Ki-67-stained histopathology whole-slide tissue microscopic images is considered the first step in the process of proliferation rate estimation. Pathologists use eye pooling or eagle-view techniques to localize the highly stained cell-concentrated regions from the whole slide under microscope, which is called focus-point regions. This procedure leads to a high variety of interpersonal observations and time consuming, tedious work and causes inaccurate findings. The localization of focus-point regions can be addressed as a clustering problem. This paper aims to automate the localization of focus-point regions from whole-slide images using the random patch probabilistic density method. Unlike other clustering methods, random patch probabilistic density method can adaptively localize focus-point regions without predetermining the number of clusters. The proposed method was compared with the k-means and fuzzy c-means clustering methods. Our proposed method achieves a good performance, when the results were evaluated by three expert pathologists. The proposed method achieves an average false-positive rate of 0.84% for the focus-point region localization error. Moreover, regarding RPPD used to localize tissue from whole-slide images, 228 whole-slide images have been tested; 97.3% localization accuracy was achieved. PMID:25793010

  4. Adaptive localization of focus point regions via random patch probabilistic density from whole-slide, Ki-67-stained brain tumor tissue.

    PubMed

    Alomari, Yazan M; Sheikh Abdullah, Siti Norul Huda; MdZin, Reena Rahayu; Omar, Khairuddin

    2015-01-01

    Analysis of whole-slide tissue for digital pathology images has been clinically approved to provide a second opinion to pathologists. Localization of focus points from Ki-67-stained histopathology whole-slide tissue microscopic images is considered the first step in the process of proliferation rate estimation. Pathologists use eye pooling or eagle-view techniques to localize the highly stained cell-concentrated regions from the whole slide under microscope, which is called focus-point regions. This procedure leads to a high variety of interpersonal observations and time consuming, tedious work and causes inaccurate findings. The localization of focus-point regions can be addressed as a clustering problem. This paper aims to automate the localization of focus-point regions from whole-slide images using the random patch probabilistic density method. Unlike other clustering methods, random patch probabilistic density method can adaptively localize focus-point regions without predetermining the number of clusters. The proposed method was compared with the k-means and fuzzy c-means clustering methods. Our proposed method achieves a good performance, when the results were evaluated by three expert pathologists. The proposed method achieves an average false-positive rate of 0.84% for the focus-point region localization error. Moreover, regarding RPPD used to localize tissue from whole-slide images, 228 whole-slide images have been tested; 97.3% localization accuracy was achieved. PMID:25793010

  5. An overview of therapeutic approaches to brain tumor stem cells

    PubMed Central

    2012-01-01

    Primary and secondary malignant central nervous system (CNS) tumors are devastating invasive tumors able to give rise to many kinds of differentiated tumor cells. Glioblastoma multiform (GBM), is the most malignant brain tumor, in which its growth and persistence depend on cancer stem cells with enhanced DNA damage repair program that also induces recurrence and resists current chemo- and radiotherapies. Unlike non-tumor stem cells, tumor stem cells lack the normal mechanisms that regulate proliferation and differentiation, resulting in uncontrolled production and incomplete differentiation of tumor cells. In current paper recent developments and new researches in the field of brain tumor stem cells have been reviewed. PMID:23483074

  6. Autofluorescence of tissue surrounding malignant tumors

    NASA Astrophysics Data System (ADS)

    Lohmann, Wolfgang; Bohle, Rainer M.; Schill, Wolf-Bernhard; Vahrson, H.; Mussmann, J.

    1998-04-01

    In vitro fluorescence measurements on pap smears of ascites, pleura, or Douglas confirmed results obtained previously with different types of tissue: Cancer tissue fluoresces hardly and is surrounded by a 'fluorescence belt.' Investigations of cytological smears (e.g. Pap smears) have revealed the possible participation of granulocytes in this 'immune' reaction. Furthermore, there seems to be obvious differences in the fluorescence response of pap smears between ovarial- carcinomas and peritoneal carcinomas based on ovarial carcinoma. This observation cannot be explained yet. Because of its sensitivity and specificity the fluorescence method can be used as an additional tool for the evaluation of the tumor invasion front. Preferably it might be used for frozen sections of biopsies and surgical excisions.

  7. Stereotactic Radiosurgery in Treating Patients With Brain Tumors

    ClinicalTrials.gov

    2012-03-21

    Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

  8. Third harmonic generation imaging for fast, label-free pathology of human brain tumors

    PubMed Central

    Kuzmin, N. V.; Wesseling, P.; Hamer, P. C. de Witt; Noske, D. P.; Galgano, G. D.; Mansvelder, H. D.; Baayen, J. C.; Groot, M. L.

    2016-01-01

    In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies. PMID:27231629

  9. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    Akimoto, Jiro

    2016-04-15

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  10. Photodynamic Therapy for Malignant Brain Tumors

    PubMed Central

    AKIMOTO, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women’s Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  11. Molecular Culprits Generating Brain Tumor Stem Cells

    PubMed Central

    Oh, Se-Yeong

    2013-01-01

    Despite current advances in multimodality therapies, such as surgery, radiotherapy, and chemotherapy, the outcome for patients with high-grade glioma remains fatal. Understanding how glioma cells resist various therapies may provide opportunities for developing new therapies. Accumulating evidence suggests that the main obstacle for successfully treating high-grade glioma is the existence of brain tumor stem cells (BTSCs), which share a number of cellular properties with adult stem cells, such as self-renewal and multipotent differentiation capabilities. Owing to their resistance to standard therapy coupled with their infiltrative nature, BTSCs are a primary cause of tumor recurrence post-therapy. Therefore, BTSCs are thought to be the main glioma cells representing a novel therapeutic target and should be eliminated to obtain successful treatment outcomes. PMID:24904883

  12. Multifocal brain radionecrosis masquerading as tumor dissemination

    SciTech Connect

    Safdari, H.; Boluix, B.; Gros, C.

    1984-01-01

    The authors report on an autopsy-proven case of multifocal widespread radionecrosis involving both cerebral hemispheres and masquerading as tumor dissemination on a CT scan done 13 months after complete resection of an oligodendroglioma followed by radiation therapy. This case demonstrates that radiation damage may be present in a CT scan as a multifocal, disseminated lesion. Since the survival of brain-tumor patients who have undergone radiation therapy is prolonged by aggressive therapy, the incidence and variability of radiation-induced complications in such cases is likely to increase. For similar reasons, the radionecrosis in such cases should be taken into consideration. A short review of the CT scan findings and diagnostic and therapeutic considerations in a case of widespread radionecrosis is presented. The need for appropriate diagnosis and subsequent life-saving management is emphasized.

  13. Positron Scanner for Locating Brain Tumors

    DOE R&D Accomplishments Database

    Rankowitz, S.; Robertson, J. S.; Higinbotham, W. A.; Rosenblum, M. J.

    1962-03-01

    A system is described that makes use of positron emitting isotopes for locating brain tumors. This system inherently provides more information about the distribution of radioactivity in the head in less time than existing scanners which use one or two detectors. A stationary circular array of 32 scintillation detectors scans a horizontal layer of the head from many directions simultaneously. The data, consisting of the number of counts in all possible coincidence pairs, are coded and stored in the memory of a Two-Dimensional Pulse-Height Analyzer. A unique method of displaying and interpreting the data is described that enables rapid approximate analysis of complex source distribution patterns. (auth)

  14. Intraoperative MRI in pediatric brain tumors.

    PubMed

    Choudhri, Asim F; Siddiqui, Adeel; Klimo, Paul; Boop, Frederick A

    2015-09-01

    Intraoperative magnetic resonance imaging (iMRI) has emerged as an important tool in guiding the surgical management of children with brain tumors. Recent advances have allowed utilization of high field strength systems, including 3-tesla MRI, resulting in diagnostic-quality scans that can be performed while the child is on the operating table. By providing information about the possible presence of residual tumor, it allows the neurosurgeon to both identify and resect any remaining tumor that is thought to be safely accessible. By fusing the newly obtained images with the surgical guidance software, the images have the added value of aiding in navigation to any residual tumor. This is important because parenchyma often shifts during surgery. It also gives the neurosurgeon insight into whether any immediate postoperative complications have occurred. If any complications have occurred, the child is already in the operating room and precious minutes lost in transport and communications are saved. In this article we review the three main approaches to an iMRI system design. We discuss the possible roles for iMRI during intraoperative planning and provide guidance to help radiologists and neurosurgeons alike in the collaborative management of these children. PMID:26346145

  15. Brain Tumor Epidemiology - A Hub within Multidisciplinary Neuro-oncology. Report on the 15th Brain Tumor Epidemiology Consortium (BTEC) Annual Meeting, Vienna, 2014.

    PubMed

    Woehrer, Adelheid; Lau, Ching C; Prayer, Daniela; Bauchet, Luc; Rosenfeld, Myrna; Capper, David; Fisher, Paul G; Kool, Marcel; Müller, Martin; Kros, Johan M; Kruchko, Carol; Wiemels, Joseph; Wrensch, Margaret; Danysh, Heather E; Zouaoui, Sonia; Heck, Julia E; Johnson, Kimberly J; Qi, Xiaoyang; O'Neill, Brian P; Afzal, Samina; Scheurer, Michael E; Bainbridge, Matthew N; Nousome, Darryl; Bahassi, El Mustapha; Hainfellner, Johannes A; Barnholtz-Sloan, Jill S

    2015-01-01

    The Brain Tumor Epidemiology Consortium (BTEC) is an open scientific forum, which fosters the development of multi-center, international and inter-disciplinary collaborations. BTEC aims to develop a better understanding of the etiology, outcomes, and prevention of brain tumors (http://epi.grants.cancer.gov/btec/). The 15th annual Brain Tumor Epidemiology Consortium Meeting, hosted by the Austrian Societies of Neuropathology and Neuro-oncology, was held on September 9 - 11, 2014 in Vienna, Austria. The meeting focused on the central role of brain tumor epidemiology within multidisciplinary neuro-oncology. Knowledge of disease incidence, outcomes, as well as risk factors is fundamental to all fields involved in research and treatment of patients with brain tumors; thus, epidemiology constitutes an important link between disciplines, indeed the very hub. This was reflected by the scientific program, which included various sessions linking brain tumor epidemiology with clinical neuro-oncology, tissue-based research, and cancer registration. Renowned experts from Europe and the United States contributed their personal perspectives stimulating further group discussions. Several concrete action plans evolved for the group to move forward until next year's meeting, which will be held at the Mayo Clinic at Rochester, MN, USA. PMID:25518914

  16. Involvement of tumor acidification in brain cancer pathophysiology

    PubMed Central

    Honasoge, Avinash; Sontheimer, Harald

    2013-01-01

    Gliomas, primary brain cancers, are characterized by remarkable invasiveness and fast growth. While they share many qualities with other solid tumors, gliomas have developed special mechanisms to convert the cramped brain space and other limitations afforded by the privileged central nervous system into pathophysiological advantages. In this review we discuss gliomas and other primary brain cancers in the context of acid-base regulation and interstitial acidification; namely, how the altered proton (H+) content surrounding these brain tumors influences tumor development in both autocrine and paracrine manners. As proton movement is directly coupled to movement of other ions, pH serves as both a regulator of cell activity as well as an indirect readout of other cellular functions. In the case of brain tumors, these processes result in pathophysiology unique to the central nervous system. We will highlight what is known about pH-sensitive processes in brain tumors in addition to gleaning insight from other solid tumors. PMID:24198789

  17. Synthetic ground truth for validation of brain tumor MRI segmentation.

    PubMed

    Prastawa, Marcel; Bullitt, Elizabeth; Gerig, Guido

    2005-01-01

    Validation and method of comparison for segmentation of magnetic resonance images (MRI) presenting pathology is a challenging task due to the lack of reliable ground truth. We propose a new method for generating synthetic multi-modal 3D brain MRI with tumor and edema, along with the ground truth. Tumor mass effect is modeled using a biomechanical model, while tumor and edema infiltration is modeled as a reaction-diffusion process that is guided by a modified diffusion tensor MRI. We propose the use of warping and geodesic interpolation on the diffusion tensors to simulate the displacement and the destruction of the white matter fibers. We also model the process where the contrast agent tends to accumulate in cortical csf regions and active tumor regions to obtain contrast enhanced T1w MR image that appear realistic. The result is simulated multi-modal MRI with ground truth available as sets of probability maps. The system will be able to generate large sets of simulation images with tumors of varying size, shape and location, and will additionally generate infiltrated and deformed healthy tissue probabilities. PMID:16685825

  18. Simulating ‘structure-function’ patterns of malignant brain tumors

    NASA Astrophysics Data System (ADS)

    Mansury, Yuri; Deisboeck, Thomas S.

    2004-01-01

    Rapid growth and extensive tissue infiltration are characteristics of highly malignant neuroepithelial brain tumors. Very little is known, however, about the existence of structure-function relationships in these types of neoplasm. Therefore, using a previously developed two-dimensional agent-based model, we have investigated the emergent patterns of multiple tumor cells that proliferate and migrate on an adaptive grid lattice, driven by a local-search mechanism and guided by the presence of distinct environmental conditions. Numerical results indicate a strong correlation between the fractal dimensions of the tumor surface and the average velocity of the tumor's spatial expansion. In particular, when the so called ‘beaten-path advantage’ intensifies, i.e., rising ‘mechanical rewards’ for cells to follow each other along preformed pathways, it results in an increase of the tumor system's fractal dimensions leading to a concomitant acceleration of its spatial expansion. Whereas cell migration is the dominant phenotype responsible for the more extensive branching patterns exhibiting higher fractal dimensions, cell proliferation appears to become more active primarily at lower fracticality associated with stronger mechanical confinements. Implications of these results for experimental and clinical cancer research are discussed.

  19. Brain tumor CT attenuation coefficients: semiquantitative analysis of histograms.

    PubMed

    Ratzka, M; Haubitz, I

    1983-01-01

    This paper reports on work in progress on semiquantitative curve analyses of histograms of brain tumors. Separation of statistical groups of attenuation values obtained by computer calculation is done separately from scanning, using histogram printouts as the data input for a programmable calculator. This method is discussed together with its results in 50 cases of malignant gliomas. The detection of hidden tissue portions and the more accurate evaluation of partial enhancement effects have been the investigators' main concerns to the present time; however, this method may allow more specific diagnosis of malignancy and changes in tumor characteristics than visual assessment alone. This has not been proven by studies that have evaluated large numbers of cases, but seems to be worth pursuing as a new approach. PMID:6410783

  20. Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform

    PubMed Central

    Ananthanarayanan, Badriprasad; Kim, Yushan; Kumar, Sanjay

    2011-01-01

    Glioblastoma multiforme (GBM) is a malignant brain tumor characterized by diffuse infiltration of single cells into the brain parenchyma, which is a process that relies in part on aberrant biochemical and biophysical interactions between tumor cells and the brain extracellular matrix (ECM). A major obstacle to understanding ECM regulation of GBM invasion is the absence of model matrix systems that recapitulate the distinct composition and physical structure of brain ECM while allowing independent control of adhesive ligand density, mechanics, and microstructure. To address this need, we synthesized brain-mimetic ECMs based on hyaluronic acid (HA) with a range of stiffnesses that encompasses normal and tumorigenic brain tissue and functionalized these materials with short Arg-Gly-Asp (RGD) peptides to facilitate cell adhesion. Scanning electron micrographs of the hydrogels revealed a dense, sheet-like microstructure with apparent nanoscale porosity similar to brain extracellular space. On flat hydrogel substrates, glioma cell spreading area and actin stress fiber assembly increased strongly with increasing density of RGD peptide. Increasing HA stiffness under constant RGD density produced similar trends and increased the speed of random motility. In a three-dimensional (3D) spheroid paradigm, glioma cells invaded HA hydrogels with morphological patterns distinct from those observed on flat surfaces or in 3D collagen-based ECMs but highly reminiscent of those seen in brain slices. This material system represents a brain-mimetic model ECM with tunable ligand density and stiffness amenable to investigations of the mechanobiological regulation of brain tumor progression. PMID:21820737

  1. Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model

    PubMed Central

    Wanjiku, Teresia; Rudek, Michelle A; Joshi, Avadhut; Gallia, Gary L.; Riggins, Gregory J.

    2015-01-01

    Purpose Mebendazole (MBZ), first used as an antiparasitic drug, shows preclinical efficacy in models of glioblastoma and medulloblastoma. Three different MBZ polymorphs (A, B and C) exist and a detailed assessment of the brain penetration, pharmacokinetics and anti-tumor properties of each individual MBZ polymorph is necessary to improve mebendazole-based brain cancer therapy. Experimental Design and Results In this study, various marketed and custom-formulated MBZ tablets were analyzed for their polymorph content by IR spectroscopy and subsequently tested in orthotopic GL261 mouse glioma model for efficacy and tolerability. The pharmacokinetics and brain concentration of MBZ polymorphs and two main metabolites were analyzed by LC-MS. We found that polymorph B and C both increased survival in a GL261 glioma model, as B exhibited greater toxicity. Polymorph A showed no benefit. Both, polymorph B and C, reached concentrations in the brain that exceeded the IC50 in GL261 cells 29-fold. In addition, polymorph C demonstrated an AUC0-24h brain-to-plasma (B/P) ratio of 0.82, whereas B showed higher plasma AUC and lower B/P ratio. In contrast, polymorph A presented markedly lower levels in the plasma and brain. Furthermore, the combination with elacridar was able to significantly improve the efficacy of polymorph C in GL261 glioma and D425 medulloblastoma models in mice. Conclusion Among MBZ polymorphs, C reaches therapeutically effective concentrations in the brain tissue and tumor with less side effects and is the better choice for brain cancer therapy. Its efficacy can be further enhanced by combination with elacridar. PMID:25862759

  2. Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors.

    PubMed

    Saucier-Sawyer, Jennifer K; Seo, Young-Eun; Gaudin, Alice; Quijano, Elias; Song, Eric; Sawyer, Andrew J; Deng, Yang; Huttner, Anita; Saltzman, W Mark

    2016-06-28

    Glioblastoma multiforme (GBM) is a fatal brain tumor characterized by infiltration beyond the margins of the main tumor mass and local recurrence after surgery. The blood-brain barrier (BBB) poses the most significant hurdle to brain tumor treatment. Convection-enhanced delivery (CED) allows for local administration of agents, overcoming the restrictions of the BBB. Recently, polymer nanoparticles have been demonstrated to penetrate readily through the healthy brain when delivered by CED, and size has been shown to be a critical factor for nanoparticle penetration. Because these brain-penetrating nanoparticles (BPNPs) have high potential for treatment of intracranial tumors since they offer the potential for cell targeting and controlled drug release after administration, here we investigated the intratumoral CED infusions of PLGA BPNPs in animals bearing either U87 or RG2 intracranial tumors. We demonstrate that the overall volume of distribution of these BPNPs was similar to that observed in healthy brains; however, the presence of tumors resulted in asymmetric and heterogeneous distribution patterns, with substantial leakage into the peritumoral tissue. Together, our results suggest that CED of BPNPs should be optimized by accounting for tumor geometry, in terms of location, size and presence of necrotic regions, to determine the ideal infusion site and parameters for individual tumors. PMID:27063424

  3. Chemotherapy for malignant brain tumors of childhood

    PubMed Central

    Gottardo, Nicholas G.; Gajjar, Amar

    2009-01-01

    During the past 3 decades, chemotherapeutic agents have been extensively evaluated for the treatment of pediatric brain tumors in a myriad of schedules, doses, and combinations. Remarkable advances in outcome have been achieved for certain groups of children, notably those with medulloblastoma, and chemotherapy has played a key role. However, improvements in survival are obtained at a high cost to quality of life. In addition, the success achieved for medulloblastoma is offset by a lack of progress for high-grade glioma. Despite decades of intensive investigation, no single chemotherapeutic regimen stands out as particularly beneficial for children with high-grade glioma, with the vast majority of these patients succumbing to their disease. A plateau in efficacy has been reached. Further treatment intensification using conventional nonspecific chemotherapy is more likely to result in additional toxicity without major advances in survival. Genomewide analysis using microarray technology has contributed significantly to our understanding of tumor biology. This knowledge has shifted the focus onto novel agents that target molecular changes crucial for tumor proliferation or survival. These selective agents are likely to be less toxic to normal cells and it is anticipated they will be more effective than the nonspecific chemotherapeutic agents currently used. PMID:18952581

  4. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors

    SciTech Connect

    Soloway, A.H.; Barth, R.F.

    1990-01-01

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  5. Regional brain glucose metabolism in patients with brain tumors before and after radiotherapy

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Lau, Y.H.

    1994-05-01

    This study was performed to measure regional glucose metabolism in nonaffected brain regions of patients with primary or metastatic brain tumors. Seven female and four male patients (mean age 51.5{plus_minus}14.0 years old) were compared with eleven age and sex matched normal subjects. None of the patients had hydrocephalus and/or increased intracranial pressure. Brain glucose metabolism was measured using FDG-PET scan. Five of the patients were reevaluated one week after receiving radiation treatment (RT) to the brain. Patients were on Decadron and/or Dilantin at the time of both scan. PET images were analyzed with a template of 115 nonoverlapping regions of interest and then grouped into eight gray matter regions on each hemisphere. Brain regions with tumors and edema shown in MR imaging were excluded. Z scores were used to compare individual patients` regional values with those of normal subjects. The number of regional values with Z scores of less than - 3.0 were considered abnormal and were quantified. The mean global glucose metabolic rate (mean of all regions) in nonaffected brain regions of patients was significantly lower than that of normal controls (32.1{plus_minus}9.0 versus 44.8{plus_minus}6.3 {mu}mol/100g/min, p<0.001). Analyses of individual subjects revealed that none of the controls and 8 of the 11 patients had at least one abnormal region. In these 8 patients the regions which were abnormal were most frequently localized in right (n=5) and left occipital (n=6) and right orbital frontal cortex (n=7) whereas the basal ganglia was not affected. Five of the patients who had repeated scans following RT showed decrements in tumor metabolism (41{plus_minus}20.5%) and a significant increase in whole brain metabolism (8.6{plus_minus}5.3%, p<0.001). The improvement in whole brain metabolism after RT suggests that the brain metabolic decrements in the patients were related to the presence of tumoral tissue and not just a medication effect.

  6. FTIR, Raman, and CARS microscopic imaging for histopathologic assessment of brain tumors

    NASA Astrophysics Data System (ADS)

    Krafft, Christoph; Bergner, Norbert; Matthäus, Christian; Romeike, Bernd; Reichart, Rupert; Kalff, Rolf; Dietzek, B.,; Popp, Jürgen

    2010-02-01

    The contribution demonstrates how the molecular contrast of Fourier transform infrared (FTIR), Raman and coherent anti-Stokes Raman scattering (CARS) microscopic imaging can be applied for the histopathological assessment of brain tumors. Human brain tissue specimens were obtained from patients undergoing neurosurgery. Thin sections of control brain tissue from an epilepsy patient and tumor tissue from a meningioma patient were prepared on calciumfluoride slides which were appropriate substrates for data acquisition in transmission and reflection mode. All CARS images correlate well with the FTIR and Raman images. Whereas CARS images were collected within seconds, exposure times were minutes for FTIR imaging and hours for Raman imaging. CARS images in the interval 2750-3000 cm-1 mainly probed spectral contributions of lipids which are important diagnostic markers of brain tumors. It was demonstrated that the CARS profile in the interval 2750-3000 cm-1 differed between the control sample and meningioma. Full spectral information could be extracted from Raman and FTIR images that enabled to distinguish different tissue types in brain tumors. Based on the current results we suggest a complementary application of FTIR, Raman and CARS imaging. FTIR and Raman imaging defines spectral regions and spectral markers that are essential for tissue classification. CARS images at different Stokes shifts or in the multiplex mode probe these spectral descriptors at video-time frame rates.

  7. Combining Microbubbles and Ultrasound for Drug Delivery to Brain Tumors: Current Progress and Overview

    PubMed Central

    Liu, Hao-Li; Fan, Ching-Hsiang; Ting, Chien-Yu; Yeh, Chih-Kuang

    2014-01-01

    Malignant glioma is one of the most challenging central nervous system (CNS) diseases, which is typically associated with high rates of recurrence and mortality. Current surgical debulking combined with radiation or chemotherapy has failed to control tumor progression or improve glioma patient survival. Microbubbles (MBs) originally serve as contrast agents in diagnostic ultrasound but have recently attracted considerable attention for therapeutic application in enhancing blood-tissue permeability for drug delivery. MB-facilitated focused ultrasound (FUS) has already been confirmed to enhance CNS-blood permeability by temporally opening the blood-brain barrier (BBB), thus has potential to enhance delivery of various kinds of therapeutic agents into brain tumors. Here we review the current preclinical studies which demonstrate the reports by using FUS with MB-facilitated drug delivery technology in brain tumor treatment. In addition, we review newly developed multifunctional theranostic MBs for FUS-induced BBB opening for brain tumor therapy. PMID:24578726

  8. Brain tumors in man and animals: report of a workshop

    SciTech Connect

    Not Available

    1986-09-01

    This report summarizes the results of a workshop on brain tumors in man and animals. Animals, especially rodents are often used as surrogates for man to detect chemicals that have the potential to induce brain tumors in man. Therefore, the workshop was focused mainly on brain tumors in the F344 rat and B6C3F1 mouse because of the frequent use of these strains in long-term carcinogenesis studies. Over 100 brain tumors in F344 rats and more than 50 brain tumors in B6C3F1 mice were reviewed and compared to tumors found in man and domestic or companion animals. In the F344 rat, spontaneous brain tumors are uncommon, most are of glial origin, and the highly undifferentiated glioblastoma multiforme, a frequent tumor of man was not found. In the B6C3F1 mouse, brain tumors are exceedingly rare. Lipomas of the choroid plexus and meningiomas together account for more than 50% of the tumors found. Both rodent strains examined have low background rates and very little variability between control groups.

  9. Intraoperative brain tumor resection cavity characterization with conoscopic holography

    NASA Astrophysics Data System (ADS)

    Simpson, Amber L.; Burgner, Jessica; Chen, Ishita; Pheiffer, Thomas S.; Sun, Kay; Thompson, Reid C.; Webster, Robert J., III; Miga, Michael I.

    2012-02-01

    Brain shift compromises the accuracy of neurosurgical image-guided interventions if not corrected by either intraoperative imaging or computational modeling. The latter requires intraoperative sparse measurements for constraining and driving model-based compensation strategies. Conoscopic holography, an interferometric technique that measures the distance of a laser light illuminated surface point from a fixed laser source, was recently proposed for non-contact surface data acquisition in image-guided surgery and is used here for validation of our modeling strategies. In this contribution, we use this inexpensive, hand-held conoscopic holography device for intraoperative validation of our computational modeling approach to correcting for brain shift. Laser range scan, instrument swabbing, and conoscopic holography data sets were collected from two patients undergoing brain tumor resection therapy at Vanderbilt University Medical Center. The results of our study indicate that conoscopic holography is a promising method for surface acquisition since it requires no contact with delicate tissues and can characterize the extents of structures within confined spaces. We demonstrate that for two clinical cases, the acquired conoprobe points align with our model-updated images better than the uncorrected images lending further evidence that computational modeling approaches improve the accuracy of image-guided surgical interventions in the presence of soft tissue deformations.

  10. Tissue Elasticity Regulated Tumor Gene Expression: Implication for Diagnostic Biomarkers of Primitive Neuroectodermal Tumor

    PubMed Central

    Vu, Long T.; Keschrumrus, Vic; Zhang, Xi; Zhong, Jiang F.; Su, Qingning; Kabeer, Mustafa H.; Loudon, William G.; Li, Shengwen Calvin

    2015-01-01

    Background The tumor microenvironment consists of both physical and chemical factors. Tissue elasticity is one physical factor contributing to the microenvironment of tumor cells. To test the importance of tissue elasticity in cell culture, primitive neuroectodermal tumor (PNET) stem cells were cultured on soft polyacrylamide (PAA) hydrogel plates that mimics the elasticity of brain tissue compared with PNET on standard polystyrene (PS) plates. We report the molecular profiles of PNET grown on either PAA or PS. Methodology/Principal Findings A whole-genome microarray profile of transcriptional expression between the two culture conditions was performed as a way to probe effects of substrate on cell behavior in culture. The results showed more genes downregulated on PAA compared to PS. This led us to propose microRNA (miRNA) silencing as a potential mechanism for downregulation. Bioinformatic analysis predicted a greater number of miRNA binding sites from the 3' UTR of downregulated genes and identified as specific miRNA binding sites that were enriched when cells were grown on PAA—this supports the hypothesis that tissue elasticity plays a role in influencing miRNA expression. Thus, Dicer was examined to determine if miRNA processing was affected by tissue elasticity. Dicer genes were downregulated on PAA and had multiple predicted miRNA binding sites in its 3' UTR that matched the miRNA binding sites found enriched on PAA. Many differentially regulated genes were found to be present on PS but downregulated on PAA were mapped onto intron sequences. This suggests expression of alternative polyadenylation sites within intron regions that provide alternative 3' UTRs and alternative miRNA binding sites. This results in tissue specific transcriptional downregulation of mRNA in humans by miRNA. We propose a mechanism, driven by the physical characteristics of the microenvironment by which downregulation of genes occur. We found that tissue elasticity-mediated cytokines

  11. Identification of primary tumors of brain metastases by SIMCA classification of IR spectroscopic images.

    PubMed

    Krafft, Christoph; Shapoval, Larysa; Sobottka, Stephan B; Geiger, Kathrin D; Schackert, Gabriele; Salzer, Reiner

    2006-07-01

    Brain metastases are secondary intracranial lesions which occur more frequently than primary brain tumors. The four most abundant types of brain metastasis originate from primary tumors of lung cancer, colorectal cancer, breast cancer and renal cell carcinoma. As metastatic cells contain the molecular information of the primary tissue cells and IR spectroscopy probes the molecular fingerprint of cells, IR spectroscopy based methods constitute a new approach to determine the origin of brain metastases. IR spectroscopic images of 4 by 4 mm2 tissue areas were recorded in transmission mode by a FTIR imaging spectrometer coupled to a focal plane array detector. Unsupervised cluster analysis revealed variances within each cryosection. Selected clusters of five IR images with known diagnoses trained a supervised classification model based on the algorithm soft independent modeling of class analogies (SIMCA). This model was applied to distinguish normal brain tissue from brain metastases and to identify the primary tumor of brain metastases in 15 independent IR images. All specimens were assigned to the correct tissue class. This proof-of-concept study demonstrates that IR spectroscopy can complement established methods such as histopathology or immunohistochemistry for diagnosis. PMID:16787638

  12. Simulation of brain tumors in MR images for evaluation of segmentation efficacy.

    PubMed

    Prastawa, Marcel; Bullitt, Elizabeth; Gerig, Guido

    2009-04-01

    Obtaining validation data and comparison metrics for segmentation of magnetic resonance images (MRI) are difficult tasks due to the lack of reliable ground truth. This problem is even more evident for images presenting pathology, which can both alter tissue appearance through infiltration and cause geometric distortions. Systems for generating synthetic images with user-defined degradation by noise and intensity inhomogeneity offer the possibility for testing and comparison of segmentation methods. Such systems do not yet offer simulation of sufficiently realistic looking pathology. This paper presents a system that combines physical and statistical modeling to generate synthetic multi-modal 3D brain MRI with tumor and edema, along with the underlying anatomical ground truth, Main emphasis is placed on simulation of the major effects known for tumor MRI, such as contrast enhancement, local distortion of healthy tissue, infiltrating edema adjacent to tumors, destruction and deformation of fiber tracts, and multi-modal MRI contrast of healthy tissue and pathology. The new method synthesizes pathology in multi-modal MRI and diffusion tensor imaging (DTI) by simulating mass effect, warping and destruction of white matter fibers, and infiltration of brain tissues by tumor cells. We generate synthetic contrast enhanced MR images by simulating the accumulation of contrast agent within the brain. The appearance of the the brain tissue and tumor in MRI is simulated by synthesizing texture images from real MR images. The proposed method is able to generate synthetic ground truth and synthesized MR images with tumor and edema that exhibit comparable segmentation challenges to real tumor MRI. Such image data sets will find use in segmentation reliability studies, comparison and validation of different segmentation methods, training and teaching, or even in evaluating standards for tumor size like the RECIST criteria (response evaluation criteria in solid tumors). PMID:19119055

  13. Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS).

    PubMed

    Chandra, Subhash; Parker, Dylan J; Barth, Rolf F; Pannullo, Susan C

    2016-03-01

    Glioblastoma multiforme (GBM) is one of the deadliest forms of human brain tumors. The infiltrative pattern of growth of these tumors includes the spread of individual and/or clusters of tumor cells at some distance from the main tumor mass in parts of the brain protected by an intact blood-brain-barrier. Pathophysiological studies of GBM could be greatly enhanced by analytical techniques capable of in situ single-cell resolution measurements of infiltrating tumor cells. Magnesium homeostasis is an area of active investigation in high grade gliomas. In the present study, we have used the F98 rat glioma as a model of human GBM and an elemental/isotopic imaging technique of secondary ion mass spectrometry, a CAMECA IMS-3f ion microscope, for studying Mg distribution with single-cell resolution in freeze-dried brain tissue cryosections. Quantitative observations were made on tumor cells in the main tumor mass, contiguous brain tissue, and infiltrating tumor cells in adjacent normal brain. The brain tissue contained a significantly lower total Mg concentration of 4.70 ± 0.93 mmol/kg wet weight (mean ± SD) in comparison to 11.64 ± 1.96 mmol/kg wet weight in tumor cells of the main tumor mass and 10.72 ± 1.76 mmol/kg wet weight in infiltrating tumor cells (p < 0.05). The nucleus of individual tumor cells contained elevated levels of bound Mg. These observations have established that there was enhanced influx and increased binding of Mg in tumor cells. They provide strong support for further investigation of altered Mg homeostasis and activation of Mg-transporting channels in GBMs as possible therapeutic targets. PMID:26703785

  14. Early CT findings after interstitial radiation therapy for primary malignant brain tumors

    SciTech Connect

    Tolly, T.L.; Bruckman, J.E.; Czarnecki, D.J.; Frazin, L.J.; Lewis, H.J.; Richards, M.J.; Adamkiewicz, J.J. Jr.

    1988-11-01

    The CT findings after interstitial radiation therapy for brain tumors have not been extensively described. We evaluated retrospectively the CT scans of 13 patients who were treated with brachytherapy for malignant glioma. We found no typical CT appearance that differentiates recurrent tumor from radiation effect. After undergoing brachytherapy, eight of the 13 patients scanned demonstrated enhancement of brain tissue beyond the margins of the original enhancing tumor mass. In most cases, the pattern of enhancement diminished and extended more peripherally from the central necrotic area with time. We also report a new CT finding of focal calcification developing at the site of the radioactive implant.

  15. Structural Brain Alterations in Children an Average of 5 Years after Surgery and Chemotherapy for Brain Tumors

    PubMed Central

    Nelson, Mary Baron; Macey, Paul M.; Harper, Ronald M.; Jacob, Eufemia; Patel, Sunita K.; Finlay, Jonathan L.; Nelson, Marvin D.; Compton, Peggy

    2014-01-01

    Background Young children with brain tumors are often treated with high-dose chemotherapy after surgery to avoid brain tissue injury associated with irradiation. The effects of systemic chemotherapy on healthy brain tissue in this population, however, are unclear. Our objective was to compare gray and white matter integrity using MRI procedures in children with brain tumors (n=7, mean age 8.3 years), treated with surgery and high-dose chemotherapy followed by autologous hematopoietic cell rescue (AuHCR) an average of 5.4 years earlier, to age- and gender-matched healthy controls (n=9, mean age 9.3 years). Methods Diffusion tensor imaging data were collected to evaluate tissue integrity throughout the brain, as measured by mean diffusivity (MD), a marker of glial, neuronal, and axonal status, and fractional anisotropy (FA), an index of axonal health. Individual MD and FA maps were calculated, normalized, smoothed, and compared between groups using analysis of covariance, with age and sex as covariates. Results Higher mean diffusivity values, indicative of injury, emerged in patients compared with controls (p<0.05, corrected for multiple comparisons), and were especially apparent in the central thalamus, external capsule, putamen, globus pallidus and pons. Reduced FA values in some regions did not reach significance after correction for multiple comparisons. Conclusions Children treated with surgery and high-dose chemotherapy with AuHCR for brain tumors an average of 5.4 years earlier show alterations in white and gray matter in multiple brain areas distant from the tumor site, raising the possibility for long-term consequences of the tumor or treatment. PMID:24830985

  16. Telomerase inhibitors for the treatment of brain tumors and the potential of intranasal delivery.

    PubMed

    Hashizume, Rintaro; Gupta, Nalin

    2010-04-01

    A fundamental limitation in the treatment of brain tumors is that < 1% of most therapeutic agents administered systemically are able to cross the blood-brain barrier (BBB). The development of new strategies that circumvent the BBB should increase the likelihood of tumor response to selected therapeutic agents. Intranasal delivery (IND) is a practical, noninvasive method of bypassing the BBB to deliver therapeutic agents to the brain. This technique has demonstrated promising results in the treatment of neurological disorders. Telomerase is a reverse transcriptase that is expressed in the vast majority of malignant gliomas, although not in the healthy brain. Telomerase inhibition can therefore be used as a therapeutic strategy for selectively targeting malignant gliomas. The first successful IND of a telomerase inhibitor as a therapy for brain tumors was GRN-163, an oligonucleotide N3'-->5' thiophosphoramidate telomerase inhibitor, which was successfully administered into intracerebral tumors in rats with no apparent toxicity. GRN-163 exhibited favorable tumor uptake and inhibited tumor growth, leading to prolonged lifespan in treated animals. The IND of telomerase inhibitors represents a new therapeutic approach that appears to selectively kill tumor cells, without inducing toxic effects in the surrounding healthy brain tissue. PMID:20373260

  17. A survey of MRI-based medical image analysis for brain tumor studies

    NASA Astrophysics Data System (ADS)

    Bauer, Stefan; Wiest, Roland; Nolte, Lutz-P.; Reyes, Mauricio

    2013-07-01

    MRI-based medical image analysis for brain tumor studies is gaining attention in recent times due to an increased need for efficient and objective evaluation of large amounts of data. While the pioneering approaches applying automated methods for the analysis of brain tumor images date back almost two decades, the current methods are becoming more mature and coming closer to routine clinical application. This review aims to provide a comprehensive overview by giving a brief introduction to brain tumors and imaging of brain tumors first. Then, we review the state of the art in segmentation, registration and modeling related to tumor-bearing brain images with a focus on gliomas. The objective in the segmentation is outlining the tumor including its sub-compartments and surrounding tissues, while the main challenge in registration and modeling is the handling of morphological changes caused by the tumor. The qualities of different approaches are discussed with a focus on methods that can be applied on standard clinical imaging protocols. Finally, a critical assessment of the current state is performed and future developments and trends are addressed, giving special attention to recent developments in radiological tumor assessment guidelines.

  18. Hexabrachion proteins in embryonic chicken tissues and human tumors.

    PubMed

    Erickson, H P; Taylor, H C

    1987-09-01

    Cell cultures of chicken embryo and human fibroblasts produce a large extracellular matrix molecule with a six-armed structure that we called a hexabrachion (Erickson, H. P., and J. L. Iglesias, 1984, Nature (Lond.), 311:267-269. In the present work we have determined that the myotendinous (M1) antigen described by M. Chiquet and D. M. Fambrough in chicken tissues (1984, J. Cell Biol., 98:1926-1936), and the glioma mesenchymal extracellular matrix protein described by Bourdon et al. in human tumors (Bourdon, M. A., C. J. Wikstrand, H. Furthmayr, T. J. Matthews, and D. D. Bigner, 1983, Cancer Res. 43:2796-2805) have the structure of hexabrachions. We also demonstrate that the M1 antigen is present in embryonic brain, where it was previously reported absent, and have purified hexabrachions from brain homogenates. The recently described cytotactin (Grumet, M., S. Hoffman, K. L. Crossin, and G. M. Edelman, 1985, Proc. Natl. Acad. Sci. USA, 82:8075-8079) now appears to be identical to the chicken hexabrachion protein. In a search for functional roles, we looked for a possible cell attachment activity. A strong, fibronectin-like attachment activity was present in (NH4)2SO4 precipitates of cell supernatant and sedimented with hexabrachions in glycerol gradients. Hexabrachions purified by antibody adsorption, however, had lost this activity, suggesting that it was due to a separate factor associated with hexabrachions in the gradient fractions. The combined information in the several, previously unrelated studies suggests that hexabrachions may play a role in organizing localized regions of extracellular matrix. The protein is prominently expressed at specific times and locations during embryonic development, is retained in certain adult tissues, and is reexpressed in a variety of tumors. PMID:3654758

  19. Numerical modelling and in vivo analysis of fluorescent and laser light backscattered from glial brain tumors

    NASA Astrophysics Data System (ADS)

    Savelieva, Tatiana A.; Kalyagina, Nina A.; Kholodtsova, Maria N.; Loschenov, Victor B.; Goryainov, Sergey A.; Potapov, Aleksander A.

    2012-03-01

    Brain glial tumors have peculiar features of the perifocal region extension, characterized by its indistinct area, which complicates determination of the borders for tissue resection. In the present study filter-reduced back-scattered laser light signals, compared to the data from mathematical modeling, were used for description of the brain white matter. The simulations of the scattered light distributions were performed in a Monte Carlo program using scattering and absorption parameters of the different grades of the brain glial tumors. The parameters were obtained by the Mie calculations for three main types of scatterers: myelinated axon fibers, cell nuclei and mitochondria. It was revealed that diffuse-reflected light, measured at the perifocal areas of the glial brain tumors, shows a significant difference relative to the signal, measured at the normal tissue, which signifies the possibility to provide diagnostically useful information on the tissue state, and to determine the borders of the tumor, thus to reduce the recurrence appearance. Differences in the values of ratios of diffuse reflectance from active growth parts of tumors and normal white matter can be useful for determination of the degree of tumor progress during the spectroscopic analysis.

  20. The pericyte antigen RGS5 in perivascular soft tissue tumors.

    PubMed

    Shen, Jia; Shrestha, Swati; Yen, Yu-Hsin; Scott, Michelle A; Soo, Chia; Ting, Kang; Peault, Bruno; Dry, Sarah M; James, Aaron W

    2016-01-01

    Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear lineage of differentiation, although most are presumed to originate from or differentiate to pericytes or a modified perivascular cell. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor was once hypothesized to have pericytic differentiation--although little bona fide evidence of pericytic differentiation exists. Likewise the perivascular epithelioid cell tumor (PEComa) family shares a perivascular growth pattern, but with distinctive dual myoid-melanocytic differentiation. RGS5, regulator of G-protein signaling 5, is a novel pericyte antigen with increasing use in animal models. Here, we describe the immunohistochemical expression patterns of RGS5 across perivascular soft tissue tumors, including glomus tumor (n = 6), malignant glomus tumor (n = 4), myopericytoma (n = 3), angioleiomyoma (n = 9), myofibroma (n = 4), solitary fibrous tumor (n = 10), and PEComa (n = 19). Immunohistochemical staining and semi-quantification was performed, and compared to αSMA (smooth muscle actin) expression. Results showed that glomus tumor (including malignant glomus tumor), myopericytoma, and angioleiomyoma shared a similar diffuse immunoreactivity for RGS5 and αSMA across all tumors examined. In contrast, myofibroma, solitary fibrous tumor and PEComa showed predominantly focal to absent RGS5 immunoreactivity. These findings further support a common pericytic lineage of differentiation in glomus tumors, myopericytoma and angioleiomyoma. The pericyte marker RGS5 may be of future clinical utility for the evaluation of pericytic differentiation in soft tissue tumors. PMID:26558691

  1. New treatment modalities for brain tumors in dogs and cats.

    PubMed

    Rossmeisl, John H

    2014-11-01

    Despite advancements in standard therapies, intracranial tumors remain a significant source of morbidity and mortality in veterinary and human medicine. Several newer approaches are gaining more widespread acceptance or are currently being prepared for translation from experimental to routine therapeutic use. Clinical trials in dogs with spontaneous brain tumors have contributed to the development and human translation of several novel therapeutic brain tumor approaches. PMID:25441624

  2. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2015-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  3. Identification of primary tumors of brain metastases by infrared spectroscopic imaging and linear discriminant analysis.

    PubMed

    Krafft, Christoph; Shapoval, Larysa; Sobottka, Stephan B; Schackert, Gabriele; Salzer, Reiner

    2006-06-01

    This study applies infrared (IR) spectroscopy to distinguish normal brain tissue from brain metastases and to determine the primary tumor of four frequent brain metastases such as lung cancer, colorectal cancer, breast cancer, and renal cell carcinoma. Standard methods sometimes fail to identify the origin of brain metastases. As metastatic cells contain the molecular information of the primary tissue cells and IR spectroscopy probes the molecular fingerprint of cells, IR spectroscopy based methods constitute a new approach to determine the primary tumor of a brain metastasis. IR spectroscopic images were recorded by a FTIR spectrometer equipped with a macro sample chamber and coupled to a focal plane array detector. Unsupervised cluster analysis of IR images revealed variances within each sample and between samples of the same tissue type. Cluster averaged IR spectra of tissue classes with known diagnoses were selected to develop a metric with eight variables. These data trained a supervised classification model based on linear discriminant analysis that was used to identify the origin of 20 cryosections including one brain metastasis with an unknown primary tumor. PMID:16700626

  4. [MRI with dynamic contrast enhancement in brain tumors].

    PubMed

    Panfilenko, A F; Iakovlev, S A; Pozdniakov, A V; Tiumin, L A; Shcherbuk, A Iu

    2013-01-01

    Magnetic resonance imaging (MRI) is the leading method of radiation diagnosis of brain tumors. In conditions of the artificial contrast enhancement there are more clearly differentiated the boundaries of the tumor node on the back of peritumorous edema and identified structural features of the tumor. The purpose of this study was to examine indicators of the dynamics of accumulation and removal of contrast agents by brain tumors in MRI technique with dynamic contrast and identify opportunities of this method in the differential diagnosis of various types of tumors. PMID:23814831

  5. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  6. Ex vivo brain tumor analysis using spectroscopic optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lenz, Marcel; Krug, Robin; Welp, Hubert; Schmieder, Kirsten; Hofmann, Martin R.

    2016-03-01

    A big challenge during neurosurgeries is to distinguish between healthy tissue and cancerous tissue, but currently a suitable non-invasive real time imaging modality is not available. Optical Coherence Tomography (OCT) is a potential technique for such a modality. OCT has a penetration depth of 1-2 mm and a resolution of 1-15 μm which is sufficient to illustrate structural differences between healthy tissue and brain tumor. Therefore, we investigated gray and white matter of healthy central nervous system and meningioma samples with a Spectral Domain OCT System (Thorlabs Callisto). Additional OCT images were generated after paraffin embedding and after the samples were cut into 10 μm thin slices for histological investigation with a bright field microscope. All samples were stained with Hematoxylin and Eosin. In all cases B-scans and 3D images were made. Furthermore, a camera image of the investigated area was made by the built-in video camera of our OCT system. For orientation, the backsides of all samples were marked with blue ink. The structural differences between healthy tissue and meningioma samples were most pronounced directly after removal. After paraffin embedding these differences diminished. A correlation between OCT en face images and microscopy images can be seen. In order to increase contrast, post processing algorithms were applied. Hence we employed Spectroscopic OCT, pattern recognition algorithms and machine learning algorithms such as k-means Clustering and Principal Component Analysis.

  7. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    PubMed

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population. PMID:26184082

  8. Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

    PubMed Central

    Kim, Eugene; Zhang, Jiangyang; Hong, Karen; Benoit, Nicole E; Pathak, Arvind P

    2011-01-01

    Abnormal vascular phenotypes have been implicated in neuropathologies ranging from Alzheimer's disease to brain tumors. The development of transgenic mouse models of such diseases has created a crucial need for characterizing the murine neurovasculature. Although histologic techniques are excellent for imaging the microvasculature at submicron resolutions, they offer only limited coverage. It is also challenging to reconstruct the three-dimensional (3D) vasculature and other structures, such as white matter tracts, after tissue sectioning. Here, we describe a novel method for 3D whole-brain mapping of the murine vasculature using magnetic resonance microscopy (μMRI), and its application to a preclinical brain tumor model. The 3D vascular architecture was characterized by six morphologic parameters: vessel length, vessel radius, microvessel density, length per unit volume, fractional blood volume, and tortuosity. Region-of-interest analysis showed significant differences in the vascular phenotype between the tumor and the contralateral brain, as well as between postinoculation day 12 and day 17 tumors. These results unequivocally show the feasibility of using μMRI to characterize the vascular phenotype of brain tumors. Finally, we show that combining these vascular data with coregistered images acquired with diffusion-weighted MRI provides a new tool for investigating the relationship between angiogenesis and concomitant changes in the brain tumor microenvironment. PMID:21386855

  9. Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors.

    PubMed

    Kovar, Joy L; Curtis, Evan; Othman, Shadi F; Simpson, Melanie A; Olive, D Michael

    2013-09-15

    Primary brain tumors present significant challenges for surgical resection because of their location and the frequent occurrence of malignant projections extending beyond the primary tumor. Visualization of the tumor margins during surgery is critical for a favorable outcome. We report the use of IRDye 800CW chlorotoxin (CLTX) as a targeted imaging agent for brain tumors in a spontaneous mouse model of medulloblastoma, ND2:SmoA1. Specificity and functionality of the targeted agent were confirmed in cell-based assays. Tumors were detected by magnetic resonance imaging and IRDye 800CW CLTX administered to individual animals for optical imaging at 1-month increments. The integrity of the blood-brain barrier (BBB) was measured by Evan's Blue perfusion prior to sacrifice. Results show that IRDye 800CW CLTX specifically targeted tumor tissue. The extravasation of Evan's Blue was observed in all tumors, suggesting that the presence of the tumors can introduce alterations in the permeability of the BBB. Because increased vascular permeability was observed early in the disease model, larger dye-labeled imaging agents that exceed current BBB size restrictions may warrant renewed consideration as candidates for tumor detection and surgical resection. Our study provides data characterizing in vitro and in vivo use of IRDye 800CW CLTX as a broadly applicable tumor imaging agent. PMID:23711726

  10. Soft tissue tumors of the penis: a review.

    PubMed

    Katona, Terrence M; Lopez-Beltran, Antonio; MacLennan, Gregory T; Cheng, Lirong; Montironi, Rodolfo; Cheng, Liang

    2006-08-01

    Penile soft tissue tumors comprise 5% of tumors at this site and most have been reported as isolated case reports. The purpose of this review is to aid the practicing surgical pathologist in distinguishing penile soft tissue tumors, such as sarcomatoid squamous cell carcinoma, from other prognostically and therapeutically important entities in the differential diagnosis. Clinical presentation, management, prognosis and factors influencing behavior are reviewed. The immunohistochemical profiles and salient morphologic clues that may help distinguish penile spindle cell tumors from sarcomatoid carcinomas are evaluated. Soft tissue tumors of the penis may be classified as benign or malignant, as superficial or deep and in terms of age at presentation. All are rare. The most common benign soft tissue tumors that affect the penis are vascular neoplasms, followed by tumors of neural, myoid and fibrous origin. Among reported cases, the most frequent malignant penile soft tissue tumors are Kaposi sarcoma and leiomyosarcoma. Correctly diagnosing penile soft tissue tumors is imperative, because the biologic behavior and the clinical management of these neoplasms vary considerably. Distinguishing sarcomas from sarcomatoid carcinoma and melanoma is particularly important. Accurate diagnosis is best facilitated by consideration of all available aspects of the case, including clinical information, histopathologic findings and immunohistochemical results. PMID:16927639

  11. Novel treatment strategies for brain tumors and metastases

    PubMed Central

    El-Habashy, Salma E.; Nazief, Alaa M.; Adkins, Chris E.; Wen, Ming Ming; El-Kamel, Amal H.; Hamdan, Ahmed M.; Hanafy, Amira S.; Terrell, Tori O.; Mohammad, Afroz S.; Lockman, Paul R.; Nounou, Mohamed Ismail

    2015-01-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood–brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  12. Novel treatment strategies for brain tumors and metastases.

    PubMed

    El-Habashy, Salma E; Nazief, Alaa M; Adkins, Chris E; Wen, Ming Ming; El-Kamel, Amal H; Hamdan, Ahmed M; Hanafy, Amira S; Terrell, Tori O; Mohammad, Afroz S; Lockman, Paul R; Nounou, Mohamed Ismail

    2014-05-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  13. High Toxoplasma gondii Seropositivity among Brain Tumor Patients in Korea.

    PubMed

    Jung, Bong-Kwang; Song, Hyemi; Kim, Min-Jae; Cho, Jaeeun; Shin, Eun-Hee; Chai, Jong-Yil

    2016-04-01

    Toxoplasma gondii is an intracellular protozoan that can modulate the environment of the infected host. An unfavorable environment modulated by T. gondii in the brain includes tumor microenvironment. Literature has suggested that T. gondii infection is associated with development of brain tumors. However, in Korea, epidemiological data regarding this correlation have been scarce. In this study, in order to investigate the relationship between T. gondii infection and brain tumor development, we investigated the seroprevalence of T. gondii among 93 confirmed brain tumor patients (various histological types, including meningioma and astrocytoma) in Korea using ELISA. The results revealed that T. gondii seropositivity among brain tumor patients (18.3%) was significantly (P<0.05) higher compared with that of healthy controls (8.6%). The seropositivity of brain tumor patients showed a significant age-tendency, i.e., higher in younger age group, compared with age-matched healthy controls (P<0.05). In conclusion, this study supports the close relationship between T. gondii infection and incidence of brain tumors. PMID:27180580

  14. High Toxoplasma gondii Seropositivity among Brain Tumor Patients in Korea

    PubMed Central

    Jung, Bong-Kwang; Song, Hyemi; Kim, Min-Jae; Cho, Jaeeun; Shin, Eun-Hee; Chai, Jong-Yil

    2016-01-01

    Toxoplasma gondii is an intracellular protozoan that can modulate the environment of the infected host. An unfavorable environment modulated by T. gondii in the brain includes tumor microenvironment. Literature has suggested that T. gondii infection is associated with development of brain tumors. However, in Korea, epidemiological data regarding this correlation have been scarce. In this study, in order to investigate the relationship between T. gondii infection and brain tumor development, we investigated the seroprevalence of T. gondii among 93 confirmed brain tumor patients (various histological types, including meningioma and astrocytoma) in Korea using ELISA. The results revealed that T. gondii seropositivity among brain tumor patients (18.3%) was significantly (P<0.05) higher compared with that of healthy controls (8.6%). The seropositivity of brain tumor patients showed a significant age-tendency, i.e., higher in younger age group, compared with age-matched healthy controls (P<0.05). In conclusion, this study supports the close relationship between T. gondii infection and incidence of brain tumors. PMID:27180580

  15. Development and characterization of non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) for brain tumor margining

    NASA Astrophysics Data System (ADS)

    Dahal, Sudhir

    During tumor removal surgery, due to the problems associated with obtaining high-resolution, real-time chemical images of where exactly the tumor ends and healthy tissue begins (tumor margining), it is often necessary to remove a much larger volume of tissue than the tumor itself. In the case of brain tumor surgery, however, it is extremely unsafe to remove excess tissue. Therefore, without an accurate image of the tumor margins, some of the tumor's finger-like projections are inevitably left behind in the surrounding parenchyma to grow again. For this reason, the development of techniques capable of providing high-resolution real-time images of tumor margins up to centimeters below the surface of a tissue is ideal for the diagnosis and treatment of tumors, as well as surgical guidance during brain tumor excision. A novel spectroscopic technique, non-resonant multiphoton photoacoustic spectroscopy (NMPPAS), is being developed with the capabilities of obtaining high-resolution subsurface chemical-based images of underlying tumors. This novel technique combines the strengths of multiphoton tissue spectroscopy and photoacoustic spectroscopy into a diagnostic methodology that will, ultimately, provide unparalleled chemical information and images to provide the state of sub-surface tissues. The NMPPAS technique employs near-infrared light (in the diagnostic window) to excite ultraviolet and/or visible light absorbing species deep below the tissue's surface. Once a multiphoton absorption event occurs, non-radiative relaxation processes generates a localized thermal expansion and subsequent acoustic wave that can be detected using a piezoelectric transducer. Since NMPPAS employs an acoustic detection modality, much deeper diagnoses can be performed than that is possible using current state of the art high-resolution chemical imaging techniques such as multiphoton fluorescence spectroscopy. NMPPAS was employed to differentiate between excised brain tumors (astrocytoma III

  16. Non-invasive monitoring of hemodynamic changes in orthotropic brain tumor

    NASA Astrophysics Data System (ADS)

    Kashyap, Dheerendra; Sharma, Vikrant; Liu, Hanli

    2007-02-01

    Radio surgical interventions such as Gamma Knife and Cyberknife have become attractive as therapeutic interventions. However, one of the drawbacks of cyberknife is radionecrosis, which is caused by excessive radiation to surrounding normal tissues. Radionecrosis occurs in about 10-15% of cases and could have adverse effects leading to death. Currently available imaging techniques have failed to reliably distinguish radionecrosis from tumor growth. Development of imaging techniques that could provide distinction between tumor growth and radionecrosis would give us ability to monitor effects of radiation therapy non-invasively. This paper investigates the use of near infrared spectroscopy (NIRS) as a new technique to monitor the growth of brain tumors. Brain tumors (9L glioma cell line) were implanted in right caudate nucleus of rats (250-300 gms, Male Fisher C) through a guide screw. A new algorithm was developed, which used broadband steady-state reflectance measurements made using a single source-detector pair, to quantify absolute concentrations of hemoglobin derivatives and reduced scattering coefficients. Preliminary results from the brain tumors indicated decreases in oxygen saturation, oxygenated hemoglobin concentrations and increases in deoxygenated hemoglobin concentrations with tumor growth. The study demonstrates that NIRS technology could provide an efficient, noninvasive means of monitoring vascular oxygenation dynamics of brain tumors and further facilitate investigations of efficacy of tumor treatments.

  17. Novel target for peptide-based imaging and treatment of brain tumors

    PubMed Central

    Hyvönen, Maija; Enbäck, Juulia; Huhtala, Tuulia; Lammi, Johanna; Sihto, Harri; Weisell, Janne; Joensuu, Heikki; Rosenthal-Aizman, Katri; El-Andaloussi, Samir; Langel, Ulo; Närvänen, Ale; Bergers, Gabriele; Laakkonen, Pirjo

    2014-01-01

    Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade IV) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT-imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared to the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3), as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histological grade of the tumor suggesting MDGI as a novel marker for malignant gliomas. PMID:24493698

  18. A hybrid neural network analysis of subtle brain volume differences in children surviving brain tumors.

    PubMed

    Reddick, W E; Mulhern, R K; Elkin, T D; Glass, J O; Merchant, T E; Langston, J W

    1998-05-01

    In the treatment of children with brain tumors, balancing the efficacy of treatment against commonly observed side effects is difficult because of a lack of quantitative measures of brain damage that can be correlated with the intensity of treatment. We quantitatively assessed volumes of brain parenchyma on magnetic resonance (MR) images using a hybrid combination of the Kohonen self-organizing map for segmentation and a multilayer backpropagation neural network for tissue classification. Initially, we analyzed the relationship between volumetric differences and radiologists' grading of atrophy in 80 subjects. This investigation revealed that brain parenchyma and white matter volumes significantly decreased as atrophy increased, whereas gray matter volumes had no relationship with atrophy. Next, we compared 37 medulloblastoma patients treated with surgery, irradiation, and chemotherapy to 19 patients treated with surgery and irradiation alone. This study demonstrated that, in these patients, chemotherapy had no significant effect on brain parenchyma, white matter, or gray matter volumes. We then investigated volumetric differences due to cranial irradiation in 15 medulloblastoma patients treated with surgery and radiation therapy, and compared these with a group of 15 age-matched patients with low-grade astrocytoma treated with surgery alone. With a minimum follow-up of one year after irradiation, all radiation-treated patients demonstrated significantly reduced white matter volumes, whereas gray matter volumes were relatively unchanged compared with those of age-matched patients treated with surgery alone. These results indicate that reductions in cerebral white matter: 1) are correlated significantly with atrophy; 2) are not related to chemotherapy; and 3) are correlated significantly with irradiation. This hybrid neural network analysis of subtle brain volume differences with magnetic resonance may constitute a direct measure of treatment-induced brain damage

  19. Glioma Surgical Aspirate: A Viable Source of Tumor Tissue for Experimental Research

    PubMed Central

    Day, Bryan W.; Stringer, Brett W.; Wilson, John; Jeffree, Rosalind L.; Jamieson, Paul R.; Ensbey, Kathleen S.; Bruce, Zara C.; Inglis, Po; Allan, Suzanne; Winter, Craig; Tollesson, Gert; Campbell, Scott; Lucas, Peter; Findlay, Wendy; Kadrian, David; Johnson, David; Robertson, Thomas; Johns, Terrance G.; Bartlett, Perry F.; Osborne, Geoffrey W.; Boyd, Andrew W.

    2013-01-01

    Brain cancer research has been hampered by a paucity of viable clinical tissue of sufficient quality and quantity for experimental research. This has driven researchers to rely heavily on long term cultured cells which no longer represent the cancers from which they were derived. Resection of brain tumors, particularly at the interface between normal and tumorigenic tissue, can be carried out using an ultrasonic surgical aspirator (CUSA) that deposits liquid (blood and irrigation fluid) and resected tissue into a sterile bottle for disposal. To determine the utility of CUSA-derived glioma tissue for experimental research, we collected 48 CUSA specimen bottles from glioma patients and analyzed both the solid tissue fragments and dissociated tumor cells suspended in the liquid waste fraction. We investigated if these fractions would be useful for analyzing tumor heterogeneity, using IHC and multi-parameter flow cytometry; we also assessed culture generation and orthotopic xenograft potential. Both cell sources proved to be an abundant, highly viable source of live tumor cells for cytometric analysis, animal studies and in-vitro studies. Our findings demonstrate that CUSA tissue represents an abundant viable source to conduct experimental research and to carry out diagnostic analyses by flow cytometry or other molecular diagnostic procedures. PMID:24216981

  20. Complex permittivities of breast tumor tissues obtained from cancer surgeries

    NASA Astrophysics Data System (ADS)

    Sugitani, Takumi; Kubota, Shin-ichi; Kuroki, Shin-ichiro; Sogo, Kenta; Arihiro, Koji; Okada, Morihito; Kadoya, Takayuki; Hide, Michihiro; Oda, Miyo; Kikkawa, Takamaro

    2014-06-01

    The variability in measurements of complex permittivities of tumor tissues between multiple samples could be attributed to the volume fraction of cancer cells in the excised tumor tissue. By the use of a digital photomicrograph image and hematoxylin-eosin staining, it was found that the malignant tumor tissue was not fully occupied by the cancer cells, but the cells were distributed locally in the stroma cells depending on the growth of cancer. The results showed that the volume fraction of cancer cells in the tumor tissue had a correlation to the measured conductivity and dielectric constant in the frequency range from 1 GHz to 6 GHz. It introduces a method to understand and gauge variability in measurements between different tumors.

  1. ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

    PubMed Central

    Bredel, Markus; Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; Elverfeldt, Dominik v.; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.

    2014-01-01

    BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR

  2. Predictive analysis of optical ablation in several dermatological tumoral tissues

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Blanco-Gutiérrez, A.; Salas-García, I.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2013-06-01

    Optical techniques for treatment and characterization of biological tissues are revolutionizing several branches of medical praxis, for example in ophthalmology or dermatology. The non-invasive, non-contact and non-ionizing character of optical radiation makes it specially suitable for these applications. Optical radiation can be employed in medical ablation applications, either for tissue resection or surgery. Optical ablation may provide a controlled and clean cut on a biological tissue. This is particularly relevant in tumoral tissue resection, where a small amount of cancerous cells could make the tumor appear again. A very important aspect of tissue optical ablation is then the estimation of the affected volume. In this work we propose a complete predictive model of tissue ablation that provides an estimation of the resected volume. The model is based on a Monte Carlo approach for the optical propagation of radiation inside the tissue, and a blow-off model for tissue ablation. This model is applied to several types of dermatological tumoral tissues, specifically squamous cells, basocellular and infiltrative carcinomas. The parameters of the optical source are varied and the estimated resected volume is calculated. The results for the different tumor types are presented and compared. This model can be used for surgical planning, in order to assure the complete resection of the tumoral tissue.

  3. Separation of the tumor and brain surface by "water jet" in cases of meningiomas.

    PubMed

    Toth, S; Vajda, J; Pasztor, E; Toth, Z

    1987-01-01

    In the surgery of meningiomas one of the most delicate problems is the separation of the tumor from the brain surface. The authors generally recommend microsurgery to preserve the brain surface anatomically and functionally. For this purpose we have developed a new surgical technique according to our concepts of tissue care. After excavating the tumor from inside the tumor brain surface was separated by repeated "water jets" into the tumor arachnoideal space. The "water jet" was produced by an ordinary bulb syringe. The front pressure of the jets was 300-1000 mm of water and the side pressure 100-300 mm of water. In the tumor-arachnoideal space the spreading water (phys. NaCl) separates the brain from the tumor with utmost care. We operated on 55 meningiomas of different types with the "water jet" technique. The immediate results were anatomically excellent. Intraoperative and postoperative acute and late edemas appeared only in a few cases. The functions of the nearby brain were generally preserved. The surgery was uneventful when the tumor surface was smooth and the tumor was spherical. When the tumor surface was uneven, one part of the tumor extended under the dura as a thin layer or the tumor was multilobulated with expanded vessels between the lobules, more microseparation was necessary. We compared the results of the "water jet" technique with the results of the "pre-water jet" series. The surgery with the "water jet" technique was much shorter and its results were better than those of microsurgery alone. PMID:3668608

  4. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    ClinicalTrials.gov

    2013-09-27

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  5. Multidisciplinary pediatric brain tumor clinics: the key to successful treatment?

    PubMed

    Abdel-Baki, Mohamed S; Hanzlik, Emily; Kieran, Mark W

    2015-01-01

    Tumors of the CNS are the most common solid tumors diagnosed in childhood. As technology and research in cancer care are advancing, more specialties are involved in the diagnosis, treatment and follow-up of children with brain tumors. Multidisciplinary clinics have become the standard of care for cancer care throughout the USA, and specialty clinics focused on particular cancer types are gaining attention in improving the patient outcomes and satisfaction. We will discuss the role of multidisciplinary clinics, in an attempt to create preliminary guidelines on establishing and maintaining a multidisciplinary brain tumor clinic in order to optimize the care of the patients and their families. PMID:25923018

  6. [Metastasis and progression mechanisms of soft tissue tumors].

    PubMed

    Steinestel, K; Wardelmann, E

    2015-11-01

    Invasion and metastatic dissemination of tumor cells defines prognosis not only in patients with epithelial, but also mesenchymal neoplasms. Early and clinically inapparent micrometastases occur in many patients, and the risk for metastasis correlates with the tumor subtype and histologic tumor grade. In recent years and analogous to the situation in epithelial tumors, mechanisms of tumor cell dissemination in soft tissue tumors have been increasingly understood, and it has been shown that reorganization of the actin cytoskeleton plays a key role in these processes. This review summarizes current knowledge on the mechanisms of progression and metastasis of soft tissue tumors and points out possible targets for novel anti-invasive and anti-metastatic therapies. PMID:26324521

  7. Dendrimer-mediated approaches for the treatment of brain tumor.

    PubMed

    Dwivedi, Nitin; Shah, Jigna; Mishra, Vijay; Mohd Amin, Mohd Cairul Iqbal; Iyer, Arun K; Tekade, Rakesh Kumar; Kesharwani, Prashant

    2016-05-01

    Worldwide, the cancer appeared as one of the most leading cause of morbidity and mortality. Among the various cancer types, brain tumors are most life threatening with low survival rate. Every year approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed. The dendrimeric approaches have a huge potential for diagnosis and treatment of brain tumor with targeting abilities of molecular cargoes to the tumor sites and the efficiency of crossing the blood brain barrier and penetration to brain after systemic administration. The various generations of dendrimers have been designed as novel targeted drug delivery tools for new therapies including sustained drug release, gene therapy, and antiangiogenic activities. At present era, various types of dendrimers like PAMAM, PPI, and PLL dendrimers validated them as milestones for the treatment and diagnosis of brain tumor as well as other cancers. This review highlights the recent research, opportunities, advantages, and challenges involved in development of novel dendrimeric complex for the therapy of brain tumor. PMID:26928261

  8. Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model

    PubMed Central

    MacDiarmid, Jennifer A.; Langova, Veronika; Bailey, Dale; Pattison, Scott T.; Pattison, Stacey L.; Christensen, Neil; Armstrong, Luke R.; Brahmbhatt, Vatsala N.; Smolarczyk, Katarzyna; Harrison, Matthew T.; Costa, Marylia; Mugridge, Nancy B.; Sedliarou, Ilya; Grimes, Nicholas A.; Kiss, Debra L.; Stillman, Bruce; Hann, Christine L.; Gallia, Gary L.; Graham, Robert M.; Brahmbhatt, Himanshu

    2016-01-01

    Background Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. Methodology/Principle Findings EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). Conclusions/Significance Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On

  9. NMR imaging of cell phone radiation absorption in brain tissue

    PubMed Central

    Gultekin, David H.; Moeller, Lothar

    2013-01-01

    A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

  10. NMR imaging of cell phone radiation absorption in brain tissue.

    PubMed

    Gultekin, David H; Moeller, Lothar

    2013-01-01

    A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

  11. Mimicking brain tissues by doping scatterers into gelatin tissue phantoms and determination of chemical species responsible for NMPPAS

    NASA Astrophysics Data System (ADS)

    Dahal, Sudhir; Cullum, Brian M.

    2012-06-01

    It has been shown that non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) has a great potential to be used as a high resolution surgical guidance technique during brain tumor surgery due to its ability of non-invasive or minimally invasive tumor differentiation. However, for experimental purposes associated with method validation, the use of real tissues is not always ideal because of issues such as availability, safety, storage, chemical doping, necessary control of size and shape, etc. To overcome these issues, tissue phantoms made from animal tissues and/or biochemical constituents, are often employed for such analyses. This work demonstrates the ability to develop and characterize gelatin based tissue phantoms with comparable optical and acoustic properties to real tissues by doping the phantoms with a scattering substance, 0.3 μm diameter Al2O3 particles. Using these phantoms, light scattering coefficients (μs) of 39 cm-1 have been generated, which are comparable to real brain tissue, thus making them a great alternative to real tissue for validation studies. In addition, this work also investigates the non-fluorescent species NAD+ found in the tissues, to evaluate its potential for being detected by NMPPAS. NMPPAS spectra of NAD+ shows a very promising beginning to determine other chemical species such as flavins, collagen, tryptophan, etc responsible for NMPPAS spectral signatures, associated with tumorogenesis.

  12. Cortical Plasticity in the Setting of Brain Tumors.

    PubMed

    Fisicaro, Ryan A; Jost, Ethan; Shaw, Katharina; Brennan, Nicole Petrovich; Peck, Kyung K; Holodny, Andrei I

    2016-02-01

    Cortical reorganization of function due to the growth of an adjacent brain tumor has clearly been demonstrated in a number of surgically proven cases. Such cases demonstrate the unmistakable implications for the neurosurgical treatment of brain tumors, as the cortical function may not reside where one may initially suspect based solely on the anatomical magnetic resonance imaging (MRI). Consequently, preoperative localization of eloquent areas adjacent to a brain tumor is necessary, as this may demonstrate unexpected organization, which may affect the neurosurgical approach to the lesion. However, in interpreting functional MRI studies, the interpreting physician must be cognizant of artifacts, which may limit the accuracy of functional MRI in the setting of brain tumors. PMID:26848558

  13. Uranyl phthalocyanines show promise in the treatment of brain tumors

    NASA Technical Reports Server (NTRS)

    Frigerio, N. A.

    1967-01-01

    Processes synthesize sulfonated and nonsulfonated uranyl phthalocyanines for application in neutron therapy of brain tumors. Tests indicate that the compounds are advantageous over the previously used boron and lithium compounds.

  14. Childhood Brain and Spinal Cord Tumors Treatment Overview

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  15. Treatment of Newly Diagnosed and Recurrent Childhood Brain Tumors

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain and spinal cord tumors ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  16. Gliomatosis cerebri: no evidence for a separate brain tumor entity.

    PubMed

    Herrlinger, Ulrich; Jones, David T W; Glas, Martin; Hattingen, Elke; Gramatzki, Dorothee; Stuplich, Moritz; Felsberg, Jörg; Bähr, Oliver; Gielen, Gerrit H; Simon, Matthias; Wiewrodt, Dorothee; Schabet, Martin; Hovestadt, Volker; Capper, David; Steinbach, Joachim P; von Deimling, Andreas; Lichter, Peter; Pfister, Stefan M; Weller, Michael; Reifenberger, Guido

    2016-02-01

    Gliomatosis cerebri (GC) is presently considered a distinct astrocytic glioma entity according to the WHO classification for CNS tumors. It is characterized by widespread, typically bilateral infiltration of the brain involving three or more lobes. Genetic studies of GC have to date been restricted to the analysis of individual glioma-associated genes, which revealed mutations in the isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 (TP53) genes in subsets of patients. Here, we report on a genome-wide analysis of DNA methylation and copy number aberrations in 25 GC patients. Results were compared with those obtained for 105 patients with various types of conventional, i.e., non-GC gliomas including diffuse astrocytic gliomas, oligodendrogliomas and glioblastomas. In addition, we assessed the prognostic role of methylation profiles and recurrent DNA copy number aberrations in GC patients. Our data reveal that the methylation profiles in 23 of the 25 GC tumors corresponded to either IDH mutant astrocytoma (n = 6), IDH mutant and 1p/19q codeleted oligodendroglioma (n = 5), or IDH wild-type glioblastoma including various molecular subgroups, i.e., H3F3A-G34 mutant (n = 1), receptor tyrosine kinase 1 (RTK1, n = 4), receptor tyrosine kinase 2 (classic) (RTK2, n = 2) or mesenchymal (n = 5) glioblastoma groups. Two tumors showed methylation profiles of normal brain tissue due to low tumor cell content. While histological grading (WHO grade IV vs. WHO grade II and III) was not prognostic, the molecular classification as classic/RTK2 or mesenchymal glioblastoma was associated with worse overall survival. Multivariate Cox regression analysis revealed MGMT promoter methylation as a positive prognostic factor. Taken together, DNA-based large-scale molecular profiling indicates that GC comprises a genetically and epigenetically heterogeneous group of diffuse gliomas that carry DNA methylation and copy number profiles closely matching the common molecularly

  17. Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

    NASA Astrophysics Data System (ADS)

    Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

    2015-03-01

    Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

  18. Nanoparticle-assisted photothermal ablation of brain tumor in an orthotopic canine model

    NASA Astrophysics Data System (ADS)

    Schwartz, Jon A.; Shetty, Anil M.; Price, Roger E.; Stafford, R. Jason; Wang, James C.; Uthamanthil, Rajesh K.; Pham, Kevin; McNichols, Roger J.; Coleman, Chris L.; Payne, J. Donald

    2009-02-01

    We report on a pilot study demonstrating a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photo-thermal ablation of canine Transmissible Venereal Tumor (cTVT) in a canine brain model. cTVT fragments grown in SCID mice were successfully inoculated in the parietal lobe of immuno-suppressed, mixed-breed hound dogs. A single dose of near-infrared absorbing, 150 nm nanoshells was infused intravenously and allowed time to passively accumulate in the intracranial tumors which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT suggesting that its neo-vasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, near-infrared radiation using a 3.5 W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8+/-4.1ºC. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sub-lethal temperatures of 48.6+/-1.1ºC. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Post-mortem histopathology of treated brain sections demonstrated the effectiveness and selectivity of the nanoshell-assisted thermal ablation.

  19. Brain tumor stem cells: molecular characteristics and their impact on therapy

    PubMed Central

    Schonberg, David L.; Lubelski, Daniel; Miller, Tyler E.; Rich, Jeremy N.

    2013-01-01

    Glioblastoma (GBM) is the most prevalent primary brain tumor and ranks among the most lethal of human cancers with conventional therapy offering only palliation. Great strides have been made in understanding brain cancer genetics and modeling these tumors with new targeted therapies being tested but these advances have not translated into substantially improved patient outcomes. Multiple chemotherapeutic agents, including temozolomide, the first-line treatment for glioblastoma, have been developed to kill cancer cells. However, the response to temozolomide in GBM is modest. Radiation is also moderately effective but this approach is plagued by limitations due to collateral radiation damage to healthy brain tissue and development of radioresistance. Therapeutic resistance is attributed at least in part to a cell population within the tumor that possesses stem-like characteristics and tumor propagating capabilities, referred to as cancer stem cells. Within GBM, the intratumoral heterogeneity is derived from a combination of regional genetic variance and a cellular hierarchy often regulated by distinct cancer stem cell niches, most notably perivascular and hypoxic regions. With the recent emergence as a key player in tumor biology, cancer stem cells have symbiotic relationships with the tumor microenvironment, oncogenic signaling pathways, and epigenetic modifications. The origins of cancer stem cells and their contributions to brain tumor growth and therapeutic resistance are under active investigation with novel anti-cancer stem cell therapies offering potential new hope for this lethal disease. PMID:23831316

  20. Metastatic brain tumor from urothelial carcinoma of the prostatic urethra

    PubMed Central

    Morita, Kohei; Oda, Masashi; Koyanagi, Masaomi; Saiki, Masaaki

    2016-01-01

    Background: Urothelial carcinoma occurs in the bladder, upper urinary tract, and lower urinary tract, including prostatic urethra. A majority of the reported cases of intracranial metastasis from urothelial carcinoma originates from the bladder and upper urinary tract. Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. Case Description: A 72-year-old male presented with a metastatic brain tumor and a 3-year history of urothelial carcinoma of the prostatic urethra treated with cystourethrectomy and chemotherapy with gemcitabine-cisplatin. Pathological diagnosis for tumor removal was compatible with metastatic brain tumor from urothelial carcinoma. Conclusion: Brain metastasis from urothelial carcinoma of the prostatic urethra has not yet been reported in the literature. It is an extremely rare case, however, we should be careful of brain metastasis during follow-up for urothelial carcinoma in the lower urinary tract. PMID:27512612

  1. Brain and Spinal Tumors: Hope through Research

    MedlinePlus

    ... of the CNS. Some tools used in the operating room include a surgical microscope, the endoscope (a ... cells, which support other brain function. central nervous system (CNS)—the brain and spinal cord. cerebrospinal fluid ( ...

  2. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis.

    PubMed

    Zhao, Liya; Jia, Kebin

    2016-01-01

    Early brain tumor detection and diagnosis are critical to clinics. Thus segmentation of focused tumor area needs to be accurate, efficient, and robust. In this paper, we propose an automatic brain tumor segmentation method based on Convolutional Neural Networks (CNNs). Traditional CNNs focus only on local features and ignore global region features, which are both important for pixel classification and recognition. Besides, brain tumor can appear in any place of the brain and be any size and shape in patients. We design a three-stream framework named as multiscale CNNs which could automatically detect the optimum top-three scales of the image sizes and combine information from different scales of the regions around that pixel. Datasets provided by Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized by MICCAI 2013 are utilized for both training and testing. The designed multiscale CNNs framework also combines multimodal features from T1, T1-enhanced, T2, and FLAIR MRI images. By comparison with traditional CNNs and the best two methods in BRATS 2012 and 2013, our framework shows advances in brain tumor segmentation accuracy and robustness. PMID:27069501

  3. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis

    PubMed Central

    Zhao, Liya; Jia, Kebin

    2016-01-01

    Early brain tumor detection and diagnosis are critical to clinics. Thus segmentation of focused tumor area needs to be accurate, efficient, and robust. In this paper, we propose an automatic brain tumor segmentation method based on Convolutional Neural Networks (CNNs). Traditional CNNs focus only on local features and ignore global region features, which are both important for pixel classification and recognition. Besides, brain tumor can appear in any place of the brain and be any size and shape in patients. We design a three-stream framework named as multiscale CNNs which could automatically detect the optimum top-three scales of the image sizes and combine information from different scales of the regions around that pixel. Datasets provided by Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized by MICCAI 2013 are utilized for both training and testing. The designed multiscale CNNs framework also combines multimodal features from T1, T1-enhanced, T2, and FLAIR MRI images. By comparison with traditional CNNs and the best two methods in BRATS 2012 and 2013, our framework shows advances in brain tumor segmentation accuracy and robustness. PMID:27069501

  4. Diffusion tensor imaging using a high-temperature superconducting resonator in a 3 T magnetic resonance imaging for a spontaneous rat brain tumor

    NASA Astrophysics Data System (ADS)

    Lin, In-Tsang; Yang, Hong-Chang; Chen, Jyh-Horng

    2013-02-01

    This study investigates the peri-tumor signal abnormalities of a spontaneous brain tumor in a rat by using a 4 cm high-temperature superconducting (HTS) surface resonator. Fractional anisotropy (FA) values derived from diffusion tensor imaging reflect the interstitial characteristic of the peri-lesional tissues of brain tumors. Low FA indicates interstitial tumor infiltration and tissue injury, while high FA indicates better tissue integrity. Better delineation of tissue contents obtained by the HTS surface resonator at 77 K may facilitate therapeutic strategy and improve clinical outcomes.

  5. Imaging of Brain Tumors With Paramagnetic Vesicles Targeted to Phosphatidylserine

    PubMed Central

    Winter, Patrick M.; Pearce, John; Chu, Zhengtao; McPherson, Christopher M.; Takigiku, Ray; Lee, Jing-Huei; Qi, Xiaoyang

    2014-01-01

    Purpose To investigate paramagnetic saposin C and dioleylphosphatidylserine (SapC-DOPS) vesicles as a targeted contrast agent for imaging phosphatidylserine (PS) expressed by glioblastoma multiforme (GBM) tumors. Materials and Methods Gd-DTPA-BSA/SapC-DOPS vesicles were formulated, and the vesicle diameter and relaxivity were measured. Targeting of Gd-DTPA-BSA/ SapC-DOPS vesicles to tumor cells in vitro and in vivo was compared with nontargeted paramagnetic vesicles (lacking SapC). Mice with GBM brain tumors were imaged at 3, 10, 20, and 24 h postinjection to measure the relaxation rate (R1) in the tumor and the normal brain. Results The mean diameter of vesicles was 175 nm, and the relaxivity at 7 Tesla was 3.32 (s*mM)−1 relative to the gadolinium concentration. Gd-DTPA-BSA/SapC-DOPS vesicles targeted cultured cancer cells, leading to an increased R1 and gadolinium level in the cells. In vivo, Gd-DTPA-BSA/SapC-DOPS vesicles produced a 9% increase in the R1 of GBM brain tumors in mice 10 h postinjection, but only minimal changes (1.2% increase) in the normal brain. Nontargeted paramagnetic vesicles yielded minimal change in the tumor R1 at 10 h postinjection (1.3%). Conclusion These experiments demonstrate that Gd-DTPA-BSA/SapC-DOPS vesicles can selectively target implanted brain tumors in vivo, providing noninvasive mapping of the cancer biomarker PS. PMID:24797437

  6. Sports and childhood brain tumors: Can I play?

    PubMed Central

    Perreault, Sébastien; Lober, Robert M.; Davis, Carissa; Stave, Christopher; Partap, Sonia; Fisher, Paul G.

    2014-01-01

    Background It is unknown whether children with brain tumors have a higher risk of complications while participating in sports. We sought to estimate the prevalence of such events by conducting a systematic review of the literature, and we surveyed providers involved with pediatric central nervous system (CNS) tumor patients. Methods A systematic review of the literature in the PubMed, Scopus, and Cochrane databases was conducted for original articles addressing sport-related complications in the brain-tumor population. An online questionnaire was created to survey providers involved with pediatric CNS tumor patients about their current recommendations and experience regarding sports and brain tumors. Results We retrieved 32 subjects, including 19 pediatric cases from the literature. Most lesions associated with sport complications were arachnoid cysts (n = 21), followed by glioma (n = 5). The sports in which symptom onset most commonly occurred were soccer (n = 7), football (n = 5), and running (n = 5). We surveyed 111 pediatric neuro-oncology providers. Sport restriction varied greatly from none to 14 sports. Time to return to play in sports with contact also varied considerably between providers. Rationales for limiting sports activities were partly related to subspecialty. Responders reported 9 sport-related adverse events in patients with brain tumor. Conclusions Sport-related complications are uncommon in children with brain tumors. Patients might not be at a significantly higher risk and should not need to be excluded from most sports activities. PMID:26034627

  7. Characterization of a Raman spectroscopy probe system for intraoperative brain tissue classification

    PubMed Central

    Desroches, Joannie; Jermyn, Michael; Mok, Kelvin; Lemieux-Leduc, Cédric; Mercier, Jeanne; St-Arnaud, Karl; Urmey, Kirk; Guiot, Marie-Christine; Marple, Eric; Petrecca, Kevin; Leblond, Frédéric

    2015-01-01

    A detailed characterization study is presented of a Raman spectroscopy system designed to maximize the volume of resected cancer tissue in glioma surgery based on in vivo molecular tissue characterization. It consists of a hand-held probe system measuring spectrally resolved inelastically scattered light interacting with tissue, designed and optimized for in vivo measurements. Factors such as linearity of the signal with integration time and laser power, and their impact on signal to noise ratio, are studied leading to optimal data acquisition parameters. The impact of ambient light sources in the operating room is assessed and recommendations made for optimal operating conditions. In vivo Raman spectra of normal brain, cancer and necrotic tissue were measured in 10 patients, demonstrating that real-time inelastic scattering measurements can distinguish necrosis from vital tissue (including tumor and normal brain tissue) with an accuracy of 87%, a sensitivity of 84% and a specificity of 89%. PMID:26203368

  8. Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors.

    PubMed Central

    Hatva, E.; Kaipainen, A.; Mentula, P.; Jääskeläinen, J.; Paetau, A.; Haltia, M.; Alitalo, K.

    1995-01-01

    Key growth factor-receptor interactions involved in angiogenesis are possible targets for therapy of CNS tumors. Vascular endothelial growth factor (VEGF) is a highly specific endothelial cell mitogen that has been shown to stimulate angiogenesis, a requirement for solid tumor growth. The expression of VEGF, the closely related placental growth factor (PIGF), the newly cloned endothelial high affinity VEGF receptors KDR and FLT1, and the endothelial orphan receptors FLT4 and Tie were analyzed by in situ hybridization in normal human brain tissue and in the following CNS tumors: gliomas, grades II, III, IV; meningiomas, grades I and II; and melanoma metastases to the cerebrum. VEGF mRNA was up-regulated in the majority of low grade tumors studied and was highly expressed in cells of malignant gliomas. Significantly elevated levels of Tie, KDR, and FLT1 mRNAs, but not FLT4 mRNA, were observed in malignant tumor endothelia, as well as in endothelia of tissues directly adjacent to the tumor margin. In comparison, there was little or no receptor expression in normal brain vasculature. Our results are consistent with the hypothesis that these endothelial receptors are induced during tumor progression and may play a role in tumor angiogenesis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7856749

  9. Ribosome Profiling Reveals a Cell-Type-Specific Translational Landscape in Brain Tumors

    PubMed Central

    Gonzalez, Christian; Sims, Jennifer S.; Hornstein, Nicholas; Mela, Angeliki; Garcia, Franklin; Lei, Liang; Gass, David A.; Amendolara, Benjamin; Bruce, Jeffrey N.

    2014-01-01

    Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5′-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID:25122893

  10. Gene transfer into experimental brain tumors mediated by adenovirus, herpes simplex virus, and retrovirus vectors.

    PubMed

    Boviatsis, E J; Chase, M; Wei, M X; Tamiya, T; Hurford, R K; Kowall, N W; Tepper, R I; Breakefield, X O; Chiocca, E A

    1994-02-01

    Three vectors derived from retrovirus, herpes simplex virus type 1 (HSV), and adenovirus were compared in cultured rat 9L gliosarcoma cells for gene transfer efficiency and in a 9L rat brain tumor model for histologic pattern and distribution of foreign gene delivery, as well as for associated tumor necrosis and inflammation. At a multiplicity of infection of 1, in vitro transfer of a foreign gene (lacZ from Escherichia coli) into cells was more efficient with either the replication-defective retrovirus vector or the replication-conditional thymidine kinase (TK)-deficient HSV vector than with the replication-defective adenovirus vector. In vivo, stereotactic injections of each vector into rat brain tumors revealed three main histopathologic findings: (i) retrovirus and HSV vector-mediated gene transfer was relatively selective for cells within the tumor, whereas adenovirus vector-mediated gene transfer occurred into several types of endogenous neural cells, as well as into cells within the tumor; (ii) gene transfer to multiple infiltrating tumor deposits without apparent gene transfer to intervening normal brain tissue occurred uniquely in one animal inoculated with the HSV vector, and (iii) extensive necrosis and selective inflammation in the tumor were evident with the HSV vector, whereas there was minimal evidence of tumor necrosis and inflammation with either the retrovirus or adenovirus vectors. PMID:8186298

  11. Apoptosis by Direct Current Treatment in Tumor Cells and Tissues

    NASA Astrophysics Data System (ADS)

    Kim, Hongbae; Sim, Sungbo; Ahn, Saeyoung

    2003-10-01

    Electric field induces cell fusion, electroporation on biological cells, including apoptosis. Apoptosis is expressed in a series of natural enzymatic reactions for the natural elimination of unhealthy, genetically damaged, or otherwise aberrant cells that are not needed or not advantageous to the well-being of the organism. Its markers involve cell shrinkage, activation of intracellular caspase proteases, externalization of phosphatidylserine at the plasma membrane, and fragmentation of DNA. Direct electric fields using direct current have been exploited recently to investigate its effects on tumor cells and tissues, but the mechanism of direct electric fields has not been exhibited clearly other than by electroosmosis or pH changes. Direct electric field induces apoptosis in tumor cells cultured and tumor tissues as indicated by cell shrinkage, DNA fragmentation and tumor suppression. In our experiment that direct electric field was applied to tumor tissues via two needle electrodes inserted into tumor tissue 5mm at distance in parallel, pH changes resulted from electrochemical reaction, exhibiting about pH 9.0, 1.83, 2.0 in the vicinity of cathodic and anodic electrode, and at their mid-point, respectively. DNA fragmentation of tumor tissues destructed by direct electric field was analyzed by Tunel assay by ApopTag technology. As a result of this analysis, it showed that apoptosis in tumor tissue destructed was increased up to 59.1normal(control) tissues, showing 41.1, 31.1cathodic tissues. In vitro cell survival was exhibited that it was decreased with enhancing electric current intensity in the same condition of electrical charge 5C having different time applied. We will show results of apoptosis analyzed by flow cytometry in vitro.

  12. Nonlinear microscopy and infrared and Raman microspectroscopy for brain tumor analysis

    NASA Astrophysics Data System (ADS)

    Krafft, Christoph; Dietzek, Benjamin; Meyer, Tobias; Bergner, Norbert; Romeike, Bernd F. M.; Reichart, Rupert; Kalff, Rolf; Popp, Jürgen

    2011-03-01

    Scope of the neurosurgical management of brain tumors is to remove pathological tissue, preserve normal tissue and brain functions, and collect material for neuropathological diagnosis. A prerequisite is to recognize the tumor margins as precise as possible. Scope of neuropathology is to determine the type and grade of the tumor that is an important indicator for the treatment and prognosis of the patient. In this contribution we present vibrational spectroscopic approaches to complement existing neurosurgical and neuropathological tools. First, Fourier transform infrared (FTIR) imaging is applied to obtain molecular contrast from dried, thin tissue sections. Second, Raman spectroscopic images were collected from the same specimens. Finally, coherent anti-Stokes Raman scattering (CARS) microscopic images were obtained. To demonstrate the complementary nature of the techniques results from a brain metastasis of a lung cancer are discussed. Whereas CARS images could be collected within seconds, exposure times were minutes for FTIR images and hours for Raman images. However, the CARS microscope just probed a single band near 2850 cm-1. FTIR and Raman system probed the full spectral range involving the fingerprint region below 1800 cm-1 and the stretch vibrations between 2800 and 3600 cm-1. Morphological features were resolved in the images such as solid tumor, tumor islets, necrosis and cell nuclei.

  13. Sox2: regulation of expression and contribution to brain tumors.

    PubMed

    Mansouri, Sheila; Nejad, Romina; Karabork, Merve; Ekinci, Can; Solaroglu, Ihsan; Aldape, Kenneth D; Zadeh, Gelareh

    2016-07-01

    Tumors of the CNS are composed of a complex mixture of neoplastic cells, in addition to vascular, inflammatory and stromal components. Similar to most other tumors, brain tumors contain a heterogeneous population of cells that are found at different stages of differentiation. The cancer stem cell hypothesis suggests that all tumors are composed of subpopulation of cells with stem-like properties, which are capable of self-renewal, display resistance to therapy and lead to tumor recurrence. One of the most important transcription factors that regulate cancer stem cell properties is SOX2. In this review, we focus on SOX2 and the complex network of signaling molecules and transcription factors that regulate its expression and function in brain tumor initiating cells. We also highlight important findings in the literature about the role of SOX2 in glioblastoma and medulloblastoma, where it has been more extensively studied. PMID:27230973

  14. Pretreatment with buthionine sulfoximine enhanced uptake and retention of BSH in brain tumor.

    PubMed

    Yoshida, F; Yamamoto, T; Nakai, K; Zaboronok, A; Matsuda, M; Akutsu, H; Ishikawa, E; Shirakawa, M; Matsumura, A

    2014-06-01

    To determine the influence of buthionine sulfoximine (BSO) on boron biodistribution after sulfhydryl borane (BSH) administration for boron neutron capture therapy, the effectiveness of the combination of BSO with sulfhydril- (BSH) and non-sulfhydril (B12H12 and BNH3) boron compounds, and the interval between BSO and BSH administration, the retention of boron in tissues have been evaluated using a 9L rat tumor model. Simultaneous administration of BSH and BSO showed significantly higher boron accumulation compared to that without BSO, however there was no difference in tissue boron level between B12H12 and BNH3 administration with BSO or without BSO. The longer interval (6h) between BSH and BSO administration related to the highest boron concentration in the brain and subcutaneous tumors compared to shorter intervals (0.5, 3h). Boron concentration in subcutaneous and brain tumors was maintained for 6 and 12h after the administration of BSH following BSO pretreatment. PMID:24731546

  15. Irinotecan and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases From Solid Tumors

    ClinicalTrials.gov

    2010-03-15

    Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Adults; Long-term Effects Secondary to Cancer Therapy in Children; Poor Performance Status; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  16. Biological fiducial point based registration for multiple brain tissues reconstructed from different imaging modalities

    NASA Astrophysics Data System (ADS)

    Wu, Huiqun; Zhou, Gangping; Geng, Xingyun; Zhang, Xiaofeng; Jiang, Kui; Tang, Lemin; Zhou, Guomin; Dong, Jiancheng

    2013-10-01

    With the development of computer aided navigation system, more and more tissues shall be reconstructed to provide more useful information for surgical pathway planning. In this study, we aimed to propose a registration framework for different reconstructed tissues from multi-modalities based on some fiducial points on lateral ventricles. A male patient with brain lesion was admitted and his brain scans were performed by different modalities. Then, the different brain tissues were segmented in different modality with relevant suitable algorithms. Marching cubes were calculated for three dimensional reconstructions, and then the rendered tissues were imported to a common coordinate system for registration. Four pairs of fiducial markers were selected to calculate the rotation and translation matrix using least-square measure method. The registration results were satisfied in a glioblastoma surgery planning as it provides the spatial relationship between tumors and surrounding fibers as well as vessels. Hence, our framework is of potential value for clinicians to plan surgery.

  17. Crossing the barrier: treatment of brain tumors using nanochain particles.

    PubMed

    Karathanasis, Efstathios; Ghaghada, Ketan B

    2016-09-01

    Despite advancements in surgery and radiotherapy, the aggressive forms of brain tumors, such as gliomas, are still uniformly lethal with current therapies offering only palliation complicated by significant toxicities. Gliomas are characteristically diffuse with infiltrating edges, resistant to drugs and nearly inaccessible to systemic therapies due to the brain-tumor barrier. Currently, aggressive efforts are underway to further understand brain-tumor's microenvironment and identify brain tumor cell-specific regulators amenable to pharmacologic interventions. While new potent agents are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. To tackle the drug delivery issues, a multicomponent chain-like nanoparticle has been developed. These nanochains are comprised of iron oxide nanospheres and a drug-loaded liposome chemically linked into a 100-nm linear, chain-like assembly with high precision. The nanochain possesses a unique ability to scavenge the tumor endothelium. By utilizing effective vascular targeting, the nanochains achieve rapid deposition on the vascular bed of glioma sites establishing well-distributed drug reservoirs on the endothelium of brain tumors. After reaching the target sites, an on-command, external low-power radiofrequency field can remotely trigger rapid drug release, due to mechanical disruption of the liposome, facilitating widespread and effective drug delivery into regions harboring brain tumor cells. Integration of the nanochain delivery system with the appropriate combination of complementary drugs has the potential to unfold the field and allow significant expansion of therapies for the disease where success is currently very limited. WIREs Nanomed Nanobiotechnol 2016, 8:678-695. doi: 10.1002/wnan.1387 For further resources related to this article, please visit the WIREs website. PMID:26749497

  18. [Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors].

    PubMed

    Kanygin, V V; Kichigin, A I; Gubanova, N V; Taskaev, S Yu

    2015-01-01

    Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency. PMID:26999933

  19. Convex Non-Negative Matrix Factorization for Brain Tumor Delimitation from MRSI Data

    PubMed Central

    Ortega-Martorell, Sandra; Lisboa, Paulo J. G.; Vellido, Alfredo; Simões, Rui V.; Pumarola, Martí; Julià-Sapé, Margarida; Arús, Carles

    2012-01-01

    Background Pattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation. Methodology/Principal Findings A pre-clinical study was carried out using seven brain tumor-bearing mice. Imaging and spectroscopy information was acquired from the brain tissue. A methodology is proposed to extract tissue type-specific sources from these signals by applying Convex Non-negative Matrix Factorization (Convex-NMF). Its suitability for the delimitation of pathological brain area from MRSI is experimentally confirmed by comparing the images obtained with its application to selected target regions, and to the gold standard of registered histopathology data. The former showed good accuracy for the solid tumor region (proliferation index (PI)>30%). The latter yielded (i) high sensitivity and specificity in most cases, (ii) acquisition conditions for safe thresholds in tumor and non-tumor regions (PI>30% for solid tumoral region; ≤5% for non-tumor), and (iii) fairly good results when borderline pixels were considered. Conclusions/Significance The unsupervised nature of Convex-NMF, which does not use prior information regarding the tumor area for its delimitation, places this approach one step ahead of classical label-requiring supervised methods for discrimination between tissue types, minimizing the negative effect of using mislabeled voxels. Convex-NMF also relaxes the non-negativity constraints on the observed data, which allows for a natural representation of the MRSI signal. This should help radiologists to accurately tackle one of the

  20. The roles of viruses in brain tumor initiation and oncomodulation

    PubMed Central

    Kofman, Alexander; Marcinkiewicz, Lucasz; Dupart, Evan; Lyshchev, Anton; Martynov, Boris; Ryndin, Anatolii; Kotelevskaya, Elena; Brown, Jay; Schiff, David

    2012-01-01

    While some avian retroviruses have been shown to induce gliomas in animal models, human herpesviruses, specifically, the most extensively studied cytomegalovirus, and the much less studied roseolovirus HHV-6, and Herpes simplex viruses 1 and 2, currently attract more and more attention as possible contributing or initiating factors in the development of human brain tumors. The aim of this review is to summarize and highlight the most provoking findings indicating a potential causative link between brain tumors, specifically malignant gliomas, and viruses in the context of the concepts of viral oncomodulation and the tumor stem cell origin. PMID:21720806

  1. Medical management of brain tumors and the sequelae of treatment

    PubMed Central

    Schiff, David; Lee, Eudocia Q.; Nayak, Lakshmi; Norden, Andrew D.; Reardon, David A.; Wen, Patrick Y.

    2015-01-01

    Patients with malignant brain tumors are prone to complications that negatively impact their quality of life and sometimes their overall survival as well. Tumors may directly provoke seizures, hypercoagulable states with resultant venous thromboembolism, and mood and cognitive disorders. Antitumor treatments and supportive therapies also produce side effects. In this review, we discuss major aspects of supportive care for patients with malignant brain tumors, with particular attention to management of seizures, venous thromboembolism, corticosteroids and their complications, chemotherapy including bevacizumab, and fatigue, mood, and cognitive dysfunction. PMID:25358508

  2. Evolution of Brain Tumor and Stability of Geometric Invariants

    PubMed Central

    Tawbe, K.; Cotton, F.; Vuillon, L.

    2008-01-01

    This paper presents a method to reconstruct and to calculate geometric invariants on brain tumors. The geometric invariants considered in the paper are the volume, the area, the discrete Gauss curvature, and the discrete mean curvature. The volume of a tumor is an important aspect that helps doctors to make a medical diagnosis. And as doctors seek a stable calculation, we propose to prove the stability of some invariants. Finally, we study the evolution of brain tumor as a function of time in two or three years depending on patients with MR images every three or six months. PMID:19325922

  3. Multi-fractal texture features for brain tumor and edema segmentation

    NASA Astrophysics Data System (ADS)

    Reza, S.; Iftekharuddin, K. M.

    2014-03-01

    In this work, we propose a fully automatic brain tumor and edema segmentation technique in brain magnetic resonance (MR) images. Different brain tissues are characterized using the novel texture features such as piece-wise triangular prism surface area (PTPSA), multi-fractional Brownian motion (mBm) and Gabor-like textons, along with regular intensity and intensity difference features. Classical Random Forest (RF) classifier is used to formulate the segmentation task as classification of these features in multi-modal MRIs. The segmentation performance is compared with other state-of-art works using a publicly available dataset known as Brain Tumor Segmentation (BRATS) 2012 [1]. Quantitative evaluation is done using the online evaluation tool from Kitware/MIDAS website [2]. The results show that our segmentation performance is more consistent and, on the average, outperforms other state-of-the art works in both training and challenge cases in the BRATS competition.

  4. Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases

    PubMed Central

    Jakubovic, Raphael; Sahgal, Arjun; Ruschin, Mark; Pejović-Milić, Ana; Milwid, Rachael; Aviv, Richard I.

    2015-01-01

    Purpose: To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). Methods: Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. Results: Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. Conclusion: Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio. PMID:26269612

  5. PDE5 Inhibitors Enhance Tumor Permeability and Efficacy of Chemotherapy in a Rat Brain Tumor Model

    PubMed Central

    Black, Keith L.; Yin, Dali; Ong, John M.; Hu, Jinwei; Konda, Bindu M.; Wang, Xiao; Ko, MinHee K.; Bayan, Jennifer-Ann; Sacapano, Manuel R.; Espinoza, Andreas; Morris-Irvin, Dwain K; Shu, Yan

    2008-01-01

    The blood-brain tumor barrier (BTB) significantly limits delivery of therapeutic concentrations of chemotherapy to brain tumors. A novel approach to selectively increase drug delivery is pharmacologic modulation of signaling molecules that regulate BTB permeability, such as those in cGMP signaling. Here we show that oral administration of sildenafil (Viagra) and vardenafil (Levitra), inhibitors of cGMP-specific PDE5, selectively increased tumor capillary permeability in 9L gliosarcoma-bearing rats with no significant increase in normal brain capillaries. Tumor-bearing rats treated with the chemotherapy agent, adriamycin, in combination with vardenafil survived significantly longer than rats treated with adriamycin alone. The selective increase in tumor capillary permeability appears to be mediated by a selective increase in tumor cGMP levels and increased vesicular transport through tumor capillaries, and could be attenuated by iberiotoxin, a selective inhibitor for calcium-dependent potassium (KCa) channels, that are effectors in cGMP signaling. The effect by sildenafil could be further increased by simultaneously using another BTB “opener”, bradykinin. Collectively, this data demonstrates that oral administration of PDE5 inhibitors selectively increases BTB permeability and enhance anti-tumor efficacy for a chemotherapeutic agent. These findings have significant implications for improving delivery of anti-tumor agents to brain tumors. PMID:18674521

  6. Gold nanoparticle imaging and radiotherapy of brain tumors in mice

    PubMed Central

    Hainfeld, James F; Smilowitz, Henry M; O'Connor, Michael J; Dilmanian, Farrokh Avraham; Slatkin, Daniel N

    2013-01-01

    Aim To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas. Materials & methods Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays. Results Gold uptake gave a 19:1 tumor-to-normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died. Conclusion Intravenously injected gold nanoparticles cross the blood–tumor barrier, but are largely blocked by the normal blood–brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers. PMID:23265347

  7. Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence.

    PubMed

    Widhalm, Georg

    2014-01-01

    Precise histopathological diagnosis of brain tumors is essential for the correct patient management. Furthermore, complete resection of brain tumors is associated with an improved patient prognosis. However, histopathological undergrading and incomplete tumor removal are not uncommon, especially due to insufficient intra-operative visualization of brain tumor tissue. The fluorescent dye 5-aminolevulinic acid (5-ALA) is currently applied for fluorescence-guided resections of high-grade gliomas. The value of 5-ALA-induced protoporphyrin (PpIX) fluorescence for intra-operative visualization of other tumors than high-grade gliomas remains unclear. Within the frame of this thesis, we found a significantly higher rate of complete resections of our high-grade gliomas as compared to control cases by using the newly established 5-ALA fluorescence technology at our department. Additionally, we showed that MRI spectroscopy-based chemical shift imaging (CSI) is capable to identify intratumoral high-grade glioma areas (= anaplastic foci) during navigation guided resections to avoid histopathological undergrading. However, the accuracy of navigation systems with integrated pre-operative imaging data such as CSI declines during resections due to intra-operative brainshift. In two further studies, we found that 5-ALA induced PpIX fluorescence is capable as a novel intra-operative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brainshift. Finally, we showed that the application of 5-ALA is also of relevance in needle biopsies for intra-operative identification of representative brain tumor tissue. These data indicate that 5-ALA is not only of major importance for resection of high-grade gliomas, but also for intra-operative visualization of anaplastic foci as well as representative brain tumor tissue in needle biopsies unaffected by brainshift. Consequently, this new technique might become a novel standard in brain tumor surgery that

  8. Clinical application of PET for the evaluation of brain tumors

    SciTech Connect

    Coleman, R.E.; Hoffman, J.M.; Hanson, M.W.; Sostman, H.D.; Schold, S.C. )

    1991-04-01

    The combination of FDG and PET has demonstrated clinical utility in the evaluation of patients with brain tumors. At the time of diagnosis, FDG PET provides information concerning the degree of malignancy and patient prognosis. After therapy, FDG PET is able to assess persistence of tumor, determine degree of malignancy, monitor progression, differentiate recurrence from necrosis, and assess prognosis. Other studies using PET provide information that may be clinically useful. Determination of tumor blood flow and permeability of the blood-brain barrier may help in the selection of appropriate therapy. Amino acid imaging using 11C-methionine is being evaluated in patients with brain tumors and provides different information than FDG imaging.52 references.

  9. In vivo measurement of brain tumor pH using /sup 11/CDMO and positron emission tomography

    SciTech Connect

    Rottenberg, D.A.; Ginos, J.Z.; Kearfott, K.J.; Junck, L.; Dhawan, V.; Jarden, J.O.

    1985-01-01

    In vivo measurements of regional brain tissue/tumor pH (rpH) have been accomplished in 9 patients with primary or metastatic brain tumors using (/sup 11/C)dimethyloxazolidinedione ((/sup 11/C)DMO) and positron emission tomography. Tumor rpH values ranged from 6.88 to 7.26, whereas gray matter and white matter rpH values ranged from 6.74 to 7.09 and from 6. 77 to 7.03, respectively. The results, which are consistent with reported (/sup 14/C)DMO autoradiographic measurements of brain and tumor pH, suggest that the pH microenvironment of brain tumors is not more ''acidic'' than that of normal gray or white matter.

  10. A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

    PubMed Central

    Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

    2013-01-01

    Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

  11. Neuromorphometry of primary brain tumors by magnetic resonance imaging

    PubMed Central

    Hevia-Montiel, Nidiyare; Rodriguez-Perez, Pedro I.; Lamothe-Molina, Paul J.; Arellano-Reynoso, Alfonso; Bribiesca, Ernesto; Alegria-Loyola, Marco A.

    2015-01-01

    Abstract. Magnetic resonance imaging is a technique for the diagnosis and classification of brain tumors. Discrete compactness is a morphological feature of two-dimensional and three-dimensional objects. This measure determines the compactness of a discretized object depending on the sum of the areas of the connected voxels and has been used for understanding the morphology of nonbrain tumors. We hypothesized that regarding brain tumors, we may improve the malignancy grade classification. We analyzed the values in 20 patients with different subtypes of primary brain tumors: astrocytoma, oligodendroglioma, and glioblastoma multiforme subdivided into the contrast-enhanced and the necrotic tumor regions. The preliminary results show an inverse relationship between the compactness value and the malignancy grade of gliomas. Astrocytomas exhibit a mean of 973±14, whereas oligodendrogliomas exhibit a mean of 942±21. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of 919±43, and the necrotic region presented a mean of 869±66. However, the volume and area of the enclosing surface did not show a relationship with the malignancy grade of the gliomas. Discrete compactness appears to be a stable characteristic between primary brain tumors of different malignancy grades, because similar values were obtained from different patients with the same type of tumor. PMID:26158107

  12. Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

    2007-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time

  13. Treatment of oral soft tissues benign tumors using laser

    NASA Astrophysics Data System (ADS)

    Crisan, Bogdan; Baciut, Mihaela; Crisan, Liana; Bran, Simion; Rotar, Horatiu; Dinu, Cristian; Moldovan, Iuliu; Baciut, Grigore

    2014-01-01

    The present study aimed to assess the efficacy and indications of surgical laser therapy in the treatment of oral soft tissues benign tumors compared to classic surgery. A controlled clinical study was conducted in a group of 93 patients presenting various forms of oral soft tissues benign tumors. These patients were examined pre-and postoperatively and the oral benign tumors were measured linearly and photographed. The surgery of laser-assisted biopsy excision of oral benign tumors was carried out using a diode laser device of 980 nm. In patients who received surgical laser treatment, therapeutic doses of laser to biostimulate the operated area were administered on the first day after the surgery. The interventions of conventional excision of oral soft tissues benign tumors consisted in removing them using scalpel. In patients who have received therapeutic doses of laser for biostimulation of the operated area, a faster healing of wound surfaces and tumor bed was observed during the first days after surgery. Two weeks after the surgical treatment, good healing without scarring or discomfort in the area of excision was documented. Surgical treatment of oral soft tissues benign tumors with laser assisted postoperative therapy confirms the benefits of this surgical procedure. A faster healing process of the excision area due to laser biostimulation of low intensity has been observed in patients with surgical laser assisted treatment in the postoperative period.

  14. Modeling invasion of brain tissue by glioblastoma cells: ECM alignment and motility

    NASA Astrophysics Data System (ADS)

    Sander, L. M.

    2013-03-01

    A key stage in the development of highly malignant brain tumors (Glioblastoma Multiforme) is invasion of normal brain tissue by motile cells moving through a crowded, complex environment. Evidence from in vitro experiments suggests the cell motion is accompanied by considerable deformation and alignment of the extra-cellular matrix (ECM) of the brain. In the case of breast cancer, alignment effects of this sort have been seen in vivo. We have modeled features of this system including stress confinement in the non-linear elasticity of the ECM and contact guidance of the cell motion.

  15. Measurement of steroid concentrations in brain tissue: methodological considerations.

    PubMed

    Taves, Matthew D; Ma, Chunqi; Heimovics, Sarah A; Saldanha, Colin J; Soma, Kiran K

    2011-01-01

    It is well recognized that steroids are synthesized de novo in the brain (neurosteroids). In addition, steroids circulating in the blood enter the brain. Steroids play numerous roles in the brain, such as influencing neural development, adult neuroplasticity, behavior, neuroinflammation, and neurodegenerative diseases such as Alzheimer's disease. In order to understand the regulation and functions of steroids in the brain, it is important to directly measure steroid concentrations in brain tissue. In this brief review, we discuss methods for the detection and quantification of steroids in the brain. We concisely present the major advantages and disadvantages of different technical approaches at various experimental stages: euthanasia, tissue collection, steroid extraction, steroid separation, and steroid measurement. We discuss, among other topics, the potential effects of anesthesia and saline perfusion prior to tissue collection; microdissection via Palkovits punch; solid phase extraction; chromatographic separation of steroids; and immunoassays and mass spectrometry for steroid quantification, particularly the use of mass spectrometry for "steroid profiling." Finally, we discuss the interpretation of local steroid concentrations, such as comparing steroid levels in brain tissue with those in the circulation (plasma vs. whole blood samples; total vs. free steroid levels). We also present reference values for a variety of steroids in different brain regions of adult rats. This brief review highlights some of the major methodological considerations at multiple experimental stages and provides a broad framework for designing studies that examine local steroid levels in the brain as well as other steroidogenic tissues, such as thymus, breast, and prostate. PMID:22654806

  16. Parameter estimation of brain tumors using intraoperative thermal imaging based on artificial tactile sensing in conjunction with artificial neural network

    NASA Astrophysics Data System (ADS)

    Sadeghi-Goughari, M.; Mojra, A.; Sadeghi, S.

    2016-02-01

    Intraoperative Thermal Imaging (ITI) is a new minimally invasive diagnosis technique that can potentially locate margins of brain tumor in order to achieve maximum tumor resection with least morbidity. This study introduces a new approach to ITI based on artificial tactile sensing (ATS) technology in conjunction with artificial neural networks (ANN) and feasibility and applicability of this method in diagnosis and localization of brain tumors is investigated. In order to analyze validity and reliability of the proposed method, two simulations were performed. (i) An in vitro experimental setup was designed and fabricated using a resistance heater embedded in agar tissue phantom in order to simulate heat generation by a tumor in the brain tissue; and (ii) A case report patient with parafalcine meningioma was presented to simulate ITI in the neurosurgical procedure. In the case report, both brain and tumor geometries were constructed from MRI data and tumor temperature and depth of location were estimated. For experimental tests, a novel assisted surgery robot was developed to palpate the tissue phantom surface to measure temperature variations and ANN was trained to estimate the simulated tumor’s power and depth. Results affirm that ITI based ATS is a non-invasive method which can be useful to detect, localize and characterize brain tumors.

  17. Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth.

    PubMed

    Halin Bergström, Sofia; Hägglöf, Christina; Thysell, Elin; Bergh, Anders; Wikström, Pernilla; Lundholm, Marie

    2016-01-01

    Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer. PMID:27550147

  18. Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth

    PubMed Central

    Halin Bergström, Sofia; Hägglöf, Christina; Thysell, Elin; Bergh, Anders; Wikström, Pernilla; Lundholm, Marie

    2016-01-01

    Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer. PMID:27550147

  19. Blood Brain Barrier: A Challenge for Effectual Therapy of Brain Tumors

    PubMed Central

    Bhowmik, Arijit; Ghosh, Mrinal Kanti

    2015-01-01

    Brain tumors are one of the most formidable diseases of mankind. They have only a fair to poor prognosis and high relapse rate. One of the major causes of extreme difficulty in brain tumor treatment is the presence of blood brain barrier (BBB). BBB comprises different molecular components and transport systems, which in turn create efflux machinery or hindrance for the entry of several drugs in brain. Thus, along with the conventional techniques, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle for treatment of brain tumors. In this review, we have elucidated some critical insights into the composition and function of BBB and along with it we have discussed the effective methods for delivery of drugs to the brain and therapeutic strategies overcoming the barrier. PMID:25866775

  20. Transgenic Mice Harboring SV40 T-Antigen Genes Develop Characteristic Brain Tumors

    PubMed Central

    Brinster, Ralph L.; Chen, Howard Y.; Messing, Albee; van Dyke, Terry; Levine, Arnold J.; Palmiter, Richard D.

    2016-01-01

    Summary A high percentage of transgenic mice developing from eggs microinjected with plasmids containing the SV40 early region genes and a metallothionein fusion gene develop tumors within the choroid plexus. A line of mice has been established in which nearly every affected animal succumbs to this brain tumor. Thymic hypertrophy and kidney pathology are also observed in some mice. SV40 T-antigen mRNA and protein are readily detected in affected tissues; however, SV40 T-antigen gene expression is barely detectable in unaffected tissues or in susceptible tissues prior to overt pathology, suggesting that tumorigenesis depends upon activation of the SV40 genes. Comparison of DNA from tumor tissue (or cell lines derived from tumors) with DNA from unaffected tissues reveals structural rearrangements as well as changes in DNA methylation of the foreign DNA. The SV40 genes are frequently amplified in tumor tissue, which further indicates that their expression is intimately involved in tumorigenesis in transgenic mice. PMID:6327063

  1. Backscatter and attenuation properties of mammalian brain tissues

    NASA Astrophysics Data System (ADS)

    Wijekularatne, Pushpani Vihara

    Traumatic Brain Injury (TBI) is a common category of brain injuries, which contributes to a substantial number of deaths and permanent disability all over the world. Ultrasound technology plays a major role in tissue characterization due to its low cost and portability that could be used to bridge a wide gap in the TBI diagnostic process. This research addresses the ultrasonic properties of mammalian brain tissues focusing on backscatter and attenuation. Orientation dependence and spatial averaging of data were analyzed using the same method resulting from insertion of tissue sample between a transducer and a reference reflector. Apparent backscatter transfer function (ABTF) at 1 to 10 MHz, attenuation coefficient and backscatter coefficient (BSC) at 1 to 5 MHz frequency ranges were measured on ovine brain tissue samples. The resulting ABTF was a monotonically decreasing function of frequency and the attenuation coefficient and BSC generally were increasing functions of frequency, results consistent with other soft tissues such as liver, blood and heart.

  2. Simian virus 40 transformation, malignant mesothelioma and brain tumors

    PubMed Central

    Qi, Fang; Carbone, Michele; Yang, Haining; Gaudino, Giovanni

    2011-01-01

    Simian virus 40 (SV40) is a DNA virus isolated in 1960 from contaminated polio vaccines, that induces mesotheliomas, lymphomas, brain and bone tumors, and sarcomas, including osteosarcomas, in hamsters. These same tumor types have been found to contain SV40 DNA and proteins in humans. Mesotheliomas and brain tumors are the two tumor types that have been most consistently associated with SV40, and the range of positivity has varied about from 6 to 60%, although a few reported 100% of positivity and a few reported 0%. It appears unlikely that SV40 infection alone is sufficient to cause human malignancy, as we did not observe an epidemic of cancers following the administration of SV40-contaminated vaccines. However, it seems possible that SV40 may act as a cofactor in the pathogenesis of some tumors. In vitro and animal experiments showing cocarcinogenicity between SV40 and asbestos support this hypothesis. PMID:21955238

  3. Prediction of brain tumor progression using a machine learning technique

    NASA Astrophysics Data System (ADS)

    Shen, Yuzhong; Banerjee, Debrup; Li, Jiang; Chandler, Adam; Shen, Yufei; McKenzie, Frederic D.; Wang, Jihong

    2010-03-01

    A machine learning technique is presented for assessing brain tumor progression by exploring six patients' complete MRI records scanned during their visits in the past two years. There are ten MRI series, including diffusion tensor image (DTI), for each visit. After registering all series to the corresponding DTI scan at the first visit, annotated normal and tumor regions were overlaid. Intensity value of each pixel inside the annotated regions were then extracted across all of the ten MRI series to compose a 10 dimensional vector. Each feature vector falls into one of three categories:normal, tumor, and normal but progressed to tumor at a later time. In this preliminary study, we focused on the trend of brain tumor progression during three consecutive visits, i.e., visit A, B, and C. A machine learning algorithm was trained using the data containing information from visit A to visit B, and the trained model was used to predict tumor progression from visit A to visit C. Preliminary results showed that prediction for brain tumor progression is feasible. An average of 80.9% pixel-wise accuracy was achieved for tumor progression prediction at visit C.

  4. Tumors in murine brains studied by grating-based phase contrast microtomography

    NASA Astrophysics Data System (ADS)

    Schulz, Georg; Dominietto, Marco; Kovacs, Zsofia; Schmitz, Rüdiger; Hieber, Simone E.; Thalmann, Peter; Beckmann, Felix; Müller, Bert

    2014-09-01

    Angiogenesis, i.e. the formation of vessels, is one of the key processes during tumor development. The newly formed vessels transport oxygen and nutrients from the healthy tissue to the tumor and gives tumor cells the possibility to replicate. The principle of anti-angiogenic therapy is to block angiogenic process in order to stop tumor growth. The aim of the present study is the investigation of murine glioma vascular architecture at early (7 days), intermediate (10 and 15 days) and late (23 days) stage of growth by means of grating-based phase contrast microtomography. We demonstrate that this technique yields premium contrast between healthy and cancerous parts of murine brain tissues.

  5. Iatrogenic Seeding of Tumor Cells in Thigh Soft Tissue Upon Surgical Removal of Intracranial Meningioma

    PubMed Central

    Maddah, Ghodratollah; Shabahang, Hossein; Zehi, Vahid; Sharifi Sistani, Nouriyeh; Mashhadi Nejad, Hossein

    2016-01-01

    Introduction: Meningioma is a benign and slowly-growing tumor that is responsible for 20% of brain neoplasms. It can be accompanied by some genetic disorders such as neurofibromatosis type 2 and is more common among women. As a space occupying lesion, it produces a wide range of signs and symptoms by compressing the adjacent and underlying tissues in the brain. Trauma and viruses are possible etiologies for meningioma. The ideal treatment of benign meningioma is surgical resection. Case Presentation: In this case report, we present a middle-aged man with a seeding metastasis of the cranial meningioma (after its removal) in the left thigh. During the removal operation, fascia lata had been used to repair the dura mater and the skin defect was repaired primarily. Conclusion: We believe that the occurrence of meningioma at the site of incision in the thigh is related to using the same surgical instruments for the removal of the brain tumor. PMID:27303610

  6. Regulatory T cells actively infiltrate metastatic brain tumors.

    PubMed

    Sugihara, Adam Quasar; Rolle, Cleo E; Lesniak, Maciej S

    2009-06-01

    Regulatory T cells (CD4+CD25+FoxP3+, Treg) have been shown to play a major role in suppression of the immune response to malignant gliomas. In this study, we investigated the kinetics of Treg infiltration in metastatic brain tumor models, including melanoma, breast and colon cancers. Our data indicate that both CD4+ and Treg infiltration are significantly increased throughout the time of metastatic tumor progression. These findings were recapitulated in human CNS tumor samples of metastatic melanoma and non-small cell lung carcinoma. Collectively, these data support investigating immunotherapeutic strategies targeting Treg in metastatic CNS tumors. PMID:19424570

  7. Cognitive Screening in Brain Tumors: Short but Sensitive Enough?

    PubMed Central

    Robinson, Gail A.; Biggs, Vivien; Walker, David G.

    2015-01-01

    Cognitive deficits in brain tumors are generally thought to be relatively mild and non-specific, although recent evidence challenges this notion. One possibility is that cognitive screening tools are being used to assess cognitive functions but their sensitivity to detect cognitive impairment may be limited. For improved sensitivity to recognize mild and/or focal cognitive deficits in brain tumors, neuropsychological evaluation tailored to detect specific impairments has been thought crucial. This study investigates the sensitivity of a cognitive screening tool, the Montreal Cognitive Assessment (MoCA), compared to a brief but tailored cognitive assessment (CA) for identifying cognitive deficits in an unselected primary brain tumor sample (i.e., low/high-grade gliomas, meningiomas). Performance is compared on broad measures of impairment: (a) number of patients impaired on the global screening measure or in any cognitive domain; and (b) number of cognitive domains impaired and specific analyses of MoCA-Intact and MoCA-Impaired patients on specific cognitive tests. The MoCA-Impaired group obtained lower naming and word fluency scores than the MoCA-Intact group, but otherwise performed comparably on cognitive tests. Overall, based on our results from patients with brain tumor, the MoCA has extremely poor sensitivity for detecting cognitive impairments and a brief but tailored CA is necessary. These findings will be discussed in relation to broader issues for clinical management and planning, as well as specific considerations for neuropsychological assessment of brain tumor patients. PMID:25815273

  8. Convection-enhanced delivery for the treatment of brain tumors

    PubMed Central

    Debinski, Waldemar; Tatter, Stephen B

    2013-01-01

    The brain is highly accessible for nutrients and oxygen, however delivery of drugs to malignant brain tumors is a very challenging task. Convection-enhanced delivery (CED) has been designed to overcome some of the difficulties so that pharmacological agents that would not normally cross the BBB can be used for treatment. Drugs are delivered through one to several catheters placed stereotactically directly within the tumor mass or around the tumor or the resection cavity. Several classes of drugs are amenable to this technology including standard chemotherapeutics or novel experimental targeted drugs. The first Phase III trial for CED-delivered, molecularly targeted cytotoxin in the treatment of recurrent glioblastoma multiforme has been accomplished and demonstrated objective clinical efficacy. The lessons learned from more than a decade of attempts at exploiting CED for brain cancer treatment weigh critically for its future clinical applications. The main issues center around the type of catheters used, number of catheters and their exact placement; pharmacological formulation of drugs, prescreening patients undergoing treatment and monitoring the distribution of drugs in tumors and the tumor-infiltrated brain. It is expected that optimizing CED will make this technology a permanent addition to clinical management of brain malignancies. PMID:19831841

  9. Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy.

    PubMed

    Butte, Pramod V; Fang, Qiyin; Jo, Javier A; Yong, William H; Pikul, Brian K; Black, Keith L; Marcu, Laura

    2010-01-01

    The goal of this study is to determine the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for delineation of brain tumor from surrounding normal tissue in order to assist the neurosurgeon in near-complete tumor excision. A time-domain TR-LIFS prototype apparatus (gated photomultiplier detection, fast digitizer) was used for recording tissue autofluorescence in normal cortex (NC), normal white matter (NWM), and various grades of gliomas intraoperatively. Tissue fluorescence was induced with a pulsed nitrogen laser (337 nm, 700 ps), and the intensity decay profiles were recorded in the 360- to 550-nm spectral range (10-nm interval). Histopathological analysis (hematoxylin & eosin) of the biopsy samples taken from the site of TR-LIFS measurements was used for validation of spectroscopic results. Preliminary results on 17 patients demonstrate that normal cortex (N=16) and normal white matter (N=3) show two peaks of fluorescence emission at 390 nm (lifetime=1.8+/-0.3 ns) and 460 nm (lifetime=0.8+/-0.1 ns). The 390-nm emission peak is absent in low-grade glioma (N=5; lifetime=1.1 ns) and reduced in high-grade glioma (N=9; lifetime=1.7+/-0.4 ns). The emission characteristics at 460 nm in all tissues correlated with the nicotinamide adenine dinucleotide fluorescence (peak: 440 to 460 nm; lifetime: 0.8 to 1.0 ns). These findings demonstrate the potential of using TR-LIFS as a tool for enhanced delineation of brain tumors during surgery. In addition, this study evaluates similarities and differences between TR-LIFS signatures of brain tumors obtained in vivo and those previously reported in ex vivo brain tumor specimens. PMID:20459282

  10. Intraoperative delineation of primary brain tumors using time-resolved fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Butte, Pramod V.; Fang, Qiyin; Jo, Javier A.; Yong, William H.; Pikul, Brian K.; Black, Keith L.; Marcu, Laura

    2010-03-01

    The goal of this study is to determine the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as an adjunctive tool for delineation of brain tumor from surrounding normal tissue in order to assist the neurosurgeon in near-complete tumor excision. A time-domain TR-LIFS prototype apparatus (gated photomultiplier detection, fast digitizer) was used for recording tissue autofluorescence in normal cortex (NC), normal white matter (NWM), and various grades of gliomas intraoperatively. Tissue fluorescence was induced with a pulsed nitrogen laser (337 nm, 700 ps), and the intensity decay profiles were recorded in the 360- to 550-nm spectral range (10-nm interval). Histopathological analysis (hematoxylin & eosin) of the biopsy samples taken from the site of TR-LIFS measurements was used for validation of spectroscopic results. Preliminary results on 17 patients demonstrate that normal cortex (N=16) and normal white matter (N=3) show two peaks of fluorescence emission at 390 nm (lifetime=1.8+/-0.3 ns) and 460 nm (lifetime=0.8+/-0.1 ns). The 390-nm emission peak is absent in low-grade glioma (N=5; lifetime=1.1 ns) and reduced in high-grade glioma (N=9; lifetime=1.7+/-0.4 ns). The emission characteristics at 460 nm in all tissues correlated with the nicotinamide adenine dinucleotide fluorescence (peak: 440 to 460 nm lifetime: 0.8 to 1.0 ns). These findings demonstrate the potential of using TR-LIFS as a tool for enhanced delineation of brain tumors during surgery. In addition, this study evaluates similarities and differences between TR-LIFS signatures of brain tumors obtained in vivo and those previously reported in ex vivo brain tumor specimens.

  11. Soft tissue tumors of the head and neck.

    PubMed

    Katenkamp, D

    1987-01-01

    From the tumor register of the Institute of Pathology of Jena all soft tissue tumors of the head and neck collected between 1959 and 1984 were retrieved and reclassified. 562 out of 646 tumors (87%) were benign. Three quarter of these growths could be diagnosed as nerve sheath tumors (schwannomas and neurofibromas), hemangiomas, fibrohistiocytic tumors and lipomas. 84 tumors were malignant (13%). As the most frequent subtypes we found fibrohistiocytic sarcomas (malignant fibrous histiocytomas and atypical fibroxanthomas), muscularly differentiated sarcomas (rhabdo- and leiomyosarcomas) and unclassified sarcomas. The age and sex distribution as well as the localization and histologic peculiarities were analysed and compared with findings reported in the literature. The significance of knowing such data for diagnostic and differential diagnostic considerations is stressed and exemplified. PMID:3592924

  12. Patented nanomedicines for the treatment of brain tumors.

    PubMed

    Caruso, Gerardo; Raudino, Giuseppe; Caffo, Maria

    2013-11-01

    Patients affected by malignant brain tumors present an extremely poor prognosis, notwithstanding improvements in surgery techniques and therapeutic protocols. Brain tumor treatment has been principally hampered by limited drug delivery across the blood-brain barrier (BBB). An efficacious chemotherapeutic treatment requires a pharmacological agent that can penetrate the BBB and target neoplastic cells. Nanotechnology involves the design, synthesis and characterization of materials that have a functional organization in at least one dimension on the nanometer scale. Nanoparticle systems can represent optimal devices for delivery of various drugs into the brain across the BBB. Nanoparticle drug-delivery systems can also be used to provide targeted delivery of drugs, improve bioavailability and sustain release of drugs for systemic delivery. In this patent review, the recent studies of certain nanoparticle systems in treatment of brain tumors are summarized. Common nanoparticles systems include polymeric nanoparticles, lipid nanoparticles and inorganic nanoparticles. Various patents of nanoparticle systems able to across the BBB to target brain tumors are also reported and discussed. PMID:24237240

  13. A composite hydrogel platform for the dissection of tumor cell migration at tissue interfaces.

    PubMed

    Rape, Andrew D; Kumar, Sanjay

    2014-10-01

    Glioblastoma multiforme (GBM), the most prevalent primary brain cancer, is characterized by diffuse infiltration of tumor cells into brain tissue, which severely complicates surgical resection and contributes to tumor recurrence. The most rapid mode of tissue infiltration occurs along blood vessels or white matter tracts, which represent topological interfaces thought to serve as "tracks" that speed cell migration. Despite this observation, the field lacks experimental paradigms that capture key features of these tissue interfaces and allow reductionist dissection of mechanisms of this interfacial motility. To address this need, we developed a culture system in which tumor cells are sandwiched between a fibronectin-coated ventral surface representing vascular basement membrane and a dorsal hyaluronic acid (HA) surface representing brain parenchyma. We find that inclusion of the dorsal HA surface induces formation of adhesive complexes and significantly slows cell migration relative to a free fibronectin-coated surface. This retardation is amplified by inclusion of integrin binding peptides in the dorsal layer and expression of CD44, suggesting that the dorsal surface slows migration through biochemically specific mechanisms rather than simple steric hindrance. Moreover, both the reduction in migration speed and assembly of dorsal adhesions depend on myosin activation and the stiffness of the ventral layer, implying that mechanochemical feedback directed by the ventral layer can influence adhesive signaling at the dorsal surface. PMID:25047626

  14. Culture and Isolation of Brain Tumor Initiating Cells.

    PubMed

    Vora, Parvez; Venugopal, Chitra; McFarlane, Nicole; Singh, Sheila K

    2015-01-01

    Brain tumors are typically composed of heterogeneous cells that exhibit distinct phenotypic characteristics and proliferative potentials. Only a relatively small fraction of cells in the tumor with stem cell properties, termed brain tumor initiating cells (BTICs), possess an ability to differentiate along multiple lineages, self-renew, and initiate tumors in vivo. This unit describes protocols for the culture and isolation BTICs. We applied culture conditions and assays originally used for normal neural stem cells (NSCs) in vitro to a variety of brain tumors. Using fluorescence-activated cell sorting for the neural precursor cell surface marker CD133/CD15, BTICs can be isolated and studied prospectively. Isolation of BTICs from GBM bulk tumor will enable examination of dissimilar morphologies, self-renewal capacities, tumorigenicity, and therapeutic sensitivities. As cancer is also considered a disease of unregulated self-renewal and differentiation, an understanding of BTICs is fundamental to understanding tumor growth. Ultimately, it will lead to novel drug discovery approaches that strategically target the functionally relevant BTIC population. PMID:26237571

  15. Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery

    PubMed Central

    Santagata, Sandro; Eberlin, Livia S.; Norton, Isaiah; Calligaris, David; Feldman, Daniel R.; Ide, Jennifer L.; Liu, Xiaohui; Wiley, Joshua S.; Vestal, Matthew L.; Ramkissoon, Shakti H.; Orringer, Daniel A.; Gill, Kristen K.; Dunn, Ian F.; Dias-Santagata, Dora; Ligon, Keith L.; Jolesz, Ferenc A.; Golby, Alexandra J.; Cooks, R. Graham; Agar, Nathalie Y. R.

    2014-01-01

    For many intraoperative decisions surgeons depend on frozen section pathology, a technique developed over 150 y ago. Technical innovations that permit rapid molecular characterization of tissue samples at the time of surgery are needed. Here, using desorption electrospray ionization (DESI) MS, we rapidly detect the tumor metabolite 2-hydroxyglutarate (2-HG) from tissue sections of surgically resected gliomas, under ambient conditions and without complex or time-consuming preparation. With DESI MS, we identify isocitrate dehydrogenase 1-mutant tumors with both high sensitivity and specificity within minutes, immediately providing critical diagnostic, prognostic, and predictive information. Imaging tissue sections with DESI MS shows that the 2-HG signal overlaps with areas of tumor and that 2-HG levels correlate with tumor content, thereby indicating tumor margins. Mapping the 2-HG signal onto 3D MRI reconstructions of tumors allows the integration of molecular and radiologic information for enhanced clinical decision making. We also validate the methodology and its deployment in the operating room: We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite and demonstrate the molecular analysis of surgical tissue during brain surgery. This work indicates that metabolite-imaging MS could transform many aspects of surgical care. PMID:24982150

  16. Cytomegalovirus in human brain tumors: Role in pathogenesis and potential treatment options

    PubMed Central

    Söderberg-Nauclér, Cecilia; Johnsen, John Inge

    2015-01-01

    During the last years increasing evidence implies that human cytomegalovirus (CMV) can be attributed to human malignancies arising from numerous tissues. In this perspective, we will review and discuss the potential mechanisms through which CMV infection may contribute to brain tumors by affecting tumor cell initiation, progression and metastasis formation. Recent evidence also suggests that anti-CMV treatment results in impaired tumor growth of CMV positive xenografts in animal models and potentially increased survival in CMV positive glioblastoma patients. Based on these observations and the high tumor promoting capacity of this virus, the classical and novel antiviral therapies against CMV should be revisited as they may represent a great promise for halting tumor progression and lower cancer deaths. PMID:25699229

  17. Photo-acoustic imaging of blue nanoparticle targeted brain tumor for intra-operative glioma delineation

    NASA Astrophysics Data System (ADS)

    Ray, Aniruddha; Wang, Xueding; Koo Lee, Yong-Eun; Hah, HoeJin; Kim, Gwangseong; Chen, Thomas; Orrienger, Daniel; Sagher, Oren; Kopelman, Raoul

    2011-07-01

    Distinguishing the tumor from the background neo-plastic tissue is challenging for cancer surgery such as surgical resection of glioma. Attempts have been made to use visible or fluorescent markers to delineate the tumors during surgery. However, the systemic injection of the dyes requires high dose, resulting in negative side effects. A novel method to delineate rat brain tumors intra-operatively, as well as post-operatively, using a highly sensitive photoacoustic imaging technique enhanced by tumor targeting blue nanoparticle as contrast agent is demonstrated. The nanoparticles are made of polyacrylamide (PAA) matrix with covalently linked Coomassie-Blue dye. They contain 7.0% dye and the average size is 80nm. Their surface was conjugated with F3 peptide for active tumor targeting. These nanoparticles are nontoxic, chemically inert and have long plasma circulation lifetime, making them suitable as nanodevices for imaging using photoacoustics. Experiments on phantoms and rat brains tumors ex-vivo demonstrate the high sensitivity of photoacoustic imaging in delineating the tumor, containing contrast agent at concentrations too low to be visualized by eye. The control tumors without nanoparticles did not show any enhanced signal. This study shows that photoacoustic imaging facilitated with the nanoparticle contrast agent could contribute to future surgical procedures for glioma.

  18. Biopsy of soft-tissue tumors.

    PubMed

    Shives, T C

    1993-04-01

    Biopsy is an integral part of the overall management of patients with soft-tissue sarcoma. The types of biopsy are fine needle, trocar, open incision or en bloc excision. There are advantages and disadvantages of each. Open biopsy requires strict adherence to a number of surgical principles. Proper execution requires determination of appropriate biopsy site, meticulous technique, and close collaboration with an experienced pathologist. Failure to adhere to these principles may result in untoward consequences for patients. PMID:8472430

  19. Infrared spectroscopic imaging of kidney tumor tissue

    NASA Astrophysics Data System (ADS)

    Sablinskas, V.; Steiner, G.; Koch, E.; Ceponkus, J.; Pucetaite, M.; Strazdaite, S.; Urboniene, V.; Jankevicius, F.

    2011-02-01

    Infrared spectroscopic imaging of cancerous kidney tissue was performed by means of FTIR microscopy. The spectra of thin tissue cryosections were collected with 64x64 MCT FPA detector and imaging area was increased up to 5.4×5.4 mm by mapping by means of PC controlled x,y stage. Chemical images of the samples were constructed using statistical treatment of the raw spectra. Several unsupervised and supervised statistical methods were used. The imaging results are compared with results of the standard histopathological analysis. It was concluded that application of method of cluster analysis ensures the best contrast of the images. It was found that border between cancerous and normal tissues visible in the infrared spectroscopic image corresponds with the border visible in histopathological image. Closer examination of the infrared spectroscopic image reveals that small domains of cancerous cells are found beyond the border in areas distant from the border up to 3 mm. Such domains are not visible in the histopathological images. The smallest domains found in the infrared images are approx. 60 μm.

  20. First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound.

    PubMed

    Coluccia, Daniel; Fandino, Javier; Schwyzer, Lucia; O'Gorman, Ruth; Remonda, Luca; Anon, Javier; Martin, Ernst; Werner, Beat

    2014-01-01

    Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibility of using transcranial MR-guided focused ultrasound to safely ablate substantial volumes of brain tumor tissue. PMID:25671132

  1. First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound

    PubMed Central

    2014-01-01

    Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibility of using transcranial MR-guided focused ultrasound to safely ablate substantial volumes of brain tumor tissue. PMID:25671132

  2. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    PubMed Central

    Shweikeh, Faris; Bukavina, Laura; Saeed, Kashif; Sarkis, Reem; Suneja, Aarushi; Sweiss, Fadi; Drazin, Doniel

    2014-01-01

    Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing's sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma), some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma), and a few after 36 months (chondrosarcoma and liposarcoma). Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing's sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas). Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease. PMID:24757391

  3. New strategies to deliver anticancer drugs to brain tumors

    PubMed Central

    Laquintana, Valentino; Trapani, Adriana; Denora, Nunzio; Wang, Fan; Gallo, James M.; Trapani, Giuseppe

    2009-01-01

    BACKGROUND Malignant brain tumors are among the most challenging to treat and at present there are no uniformly successful treatment strategies. Standard treatment regimens consist of maximal surgical resection followed by radiotherapy and chemotherapy. The limited survival advantage attributed to chemotherapy is partially due to low CNS penetration of antineoplastic agents across the blood-brain barrier (BBB). OBJECTIVE The objective of this paper is to review recent approaches to deliver anticancer drugs into primary brain tumors. METHODS Both preclinical and clinical strategies to circumvent the BBB are considered that includes chemical modification and colloidal carriers. CONCLUSION Analysis of the available data indicates that novel approaches may be useful for CNS delivery, yet an appreciation of pharmacokinetic issues, and improved knowledge of tumor biology will be needed to significantly impact drug delivery to the target site. PMID:19732031

  4. Diphtheria toxin-based targeted toxin therapy for brain tumors.

    PubMed

    Li, Yan Michael; Vallera, Daniel A; Hall, Walter A

    2013-09-01

    Targeted toxins (TT) are molecules that bind cell surface antigens or receptors such as the transferrin or interleukin-13 receptor that are overexpressed in cancer. After internalization, the toxin component kills the cell. These recombinant proteins consist of an antibody or carrier ligand coupled to a modified plant or bacterial toxin such as diphtheria toxin (DT). These fusion proteins are very effective against brain cancer cells that are resistant to radiation therapy and chemotherapy. TT have shown an acceptable profile for toxicity and safety in animal studies and early clinical trials have demonstrated a therapeutic response. This review summarizes the characteristics of DT-based TT, the animal studies in malignant brain tumors and early clinical trial results. Obstacles to the successful treatment of brain tumors include poor penetration into tumor, the immune response to DT and cancer heterogeneity. PMID:23695514

  5. Neurospecific proteins in the serum of patients with brain tumors.

    PubMed

    Lyubimova, N V; Toms, M G; Popova, E E; Bondarenko, Y V; Krat, V B; Kushlinskii, N E

    2011-04-01

    Neurospecific proteins S-100 and GFAP were measured in the serum of 145 patients with neural tumors and 69 healthy individuals. In patients with glyoblastomas, the concentrations of S-100 and GFAP were significantly higher than in patients with anaplastic astrocytomas, benign meningiomas, and brain metastases and in healthy individuals. Serum S-100 concentrations in patients with anaplastic astrocytomas, benign meningiomas, and brain metastases were similar; significant difference from the control was found only for patients with cerebral metastases. A specific feature of GFAP was high incidence of its detection in patients with glioblastomas (83%) compared to other groups of patients with neural tumors and healthy volunteers who demonstrated practically zero level of this protein. These findings attest to the possibility of using S-100 as an additional biochemical criterion of brain involvement in tumor patients and GFAP as a glioblastoma marker. PMID:22235430

  6. Infrared Spectra of Human Breast Tumor Tissue and Experimental Animal Tumors

    NASA Astrophysics Data System (ADS)

    Tolstorozhev, G. B.; Belkov, M. V.; Skornyakov, I. V.; Pekhnyo, V. I.; Kozachkova, A. N.; Tsarik, H. V.; Kutsenko, I. P.; Sharykina, N. I.; Butra, V. A.

    2015-01-01

    We have used Fourier transform IR spectroscopy methods to conduct comparative studies of human breast tumors and sarcoma 180 tumor grafted into mice. The IR spectral parameters used to identify tumor tissue in mice with the sarcoma 180 strain proved to be identical to the parameters for human breast tissue in cancer. In the presence of a malignant tumor in humans, the most intense C=O vibrational bands in the protein molecules are observed in the interval 1710-1680 cm-1. For a benign tumor, in the IR spectra of breast tissue the intense bands are located in the interval 1670-1650 cm-1. We spectroscopically monitored the diagnosis and the chemotherapy process using the model of sarcoma 180 in mice. As the therapeutic drugs, we used synthesized coordination compounds based on palladium complexes with diphosphonic acid derivatives. We demonstrate the promising potential of palladium complexes with zoledronic acid as an effective cytostatic. In therapy using a palladium complex with zoledronic acid, the effect of tumor growth inhibition is accompanied by a change in its spectral characteristics. The parameters of the IR spectra for tumor tissue after treatment are close to those of the IR spectra for healthy tissue.

  7. Epithelial Tumors Originate in Tumor Hotspots, a Tissue-Intrinsic Microenvironment.

    PubMed

    Tamori, Yoichiro; Suzuki, Emiko; Deng, Wu-Min

    2016-09-01

    Malignant tumors are caused by uncontrolled proliferation of transformed mutant cells that have lost the ability to maintain tissue integrity. Although a number of causative genetic backgrounds for tumor development have been discovered, the initial steps mutant cells take to escape tissue integrity and trigger tumorigenesis remain elusive. Here, we show through analysis of conserved neoplastic tumor-suppressor genes (nTSGs) in Drosophila wing imaginal disc epithelia that tumor initiation depends on tissue-intrinsic local cytoarchitectures, causing tumors to consistently originate in a specific region of the tissue. In this "tumor hotspot" where cells constitute a network of robust structures on their basal side, nTSG-deficient cells delaminate from the apical side of the epithelium and begin tumorigenic overgrowth by exploiting endogenous Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling activity. Conversely, in other regions, the "tumor coldspot" nTSG-deficient cells are extruded toward the basal side and undergo apoptosis. When the direction of delamination is reversed through suppression of RhoGEF2, an activator of the Rho family small GTPases, and JAK/STAT is activated ectopically in these coldspot nTSG-deficient cells, tumorigenesis is induced. These data indicate that two independent processes, apical delamination and JAK/STAT activation, are concurrently required for the initiation of nTSG-deficient-induced tumorigenesis. Given the conservation of the epithelial cytoarchitecture, tumorigenesis may be generally initiated from tumor hotspots by a similar mechanism. PMID:27584724

  8. Alpha shape theory for 3D visualization and volumetric measurement of brain tumor progression using magnetic resonance images.

    PubMed

    Hamoud Al-Tamimi, Mohammed Sabbih; Sulong, Ghazali; Shuaib, Ibrahim Lutfi

    2015-07-01

    Resection of brain tumors is a tricky task in surgery due to its direct influence on the patients' survival rate. Determining the tumor resection extent for its complete information via-à-vis volume and dimensions in pre- and post-operative Magnetic Resonance Images (MRI) requires accurate estimation and comparison. The active contour segmentation technique is used to segment brain tumors on pre-operative MR images using self-developed software. Tumor volume is acquired from its contours via alpha shape theory. The graphical user interface is developed for rendering, visualizing and estimating the volume of a brain tumor. Internet Brain Segmentation Repository dataset (IBSR) is employed to analyze and determine the repeatability and reproducibility of tumor volume. Accuracy of the method is validated by comparing the estimated volume using the proposed method with that of gold-standard. Segmentation by active contour technique is found to be capable of detecting the brain tumor boundaries. Furthermore, the volume description and visualization enable an interactive examination of tumor tissue and its surrounding. Admirable features of our results demonstrate that alpha shape theory in comparison to other existing standard methods is superior for precise volumetric measurement of tumor. PMID:25865822

  9. Detecting brain tumor in computed tomography images using Markov random fields and fuzzy C-means clustering techniques

    NASA Astrophysics Data System (ADS)

    Abdulbaqi, Hayder Saad; Jafri, Mohd Zubir Mat; Omar, Ahmad Fairuz; Mustafa, Iskandar Shahrim Bin; Abood, Loay Kadom

    2015-04-01

    Brain tumors, are an abnormal growth of tissues in the brain. They may arise in people of any age. They must be detected early, diagnosed accurately, monitored carefully, and treated effectively in order to optimize patient outcomes regarding both survival and quality of life. Manual segmentation of brain tumors from CT scan images is a challenging and time consuming task. Size and location accurate detection of brain tumor plays a vital role in the successful diagnosis and treatment of tumors. Brain tumor detection is considered a challenging mission in medical image processing. The aim of this paper is to introduce a scheme for tumor detection in CT scan images using two different techniques Hidden Markov Random Fields (HMRF) and Fuzzy C-means (FCM). The proposed method has been developed in this research in order to construct hybrid method between (HMRF) and threshold. These methods have been applied on 4 different patient data sets. The result of comparison among these methods shows that the proposed method gives good results for brain tissue detection, and is more robust and effective compared with (FCM) techniques.

  10. Detecting brain tumor in computed tomography images using Markov random fields and fuzzy C-means clustering techniques

    SciTech Connect

    Abdulbaqi, Hayder Saad; Jafri, Mohd Zubir Mat; Omar, Ahmad Fairuz; Mustafa, Iskandar Shahrim Bin; Abood, Loay Kadom

    2015-04-24

    Brain tumors, are an abnormal growth of tissues in the brain. They may arise in people of any age. They must be detected early, diagnosed accurately, monitored carefully, and treated effectively in order to optimize patient outcomes regarding both survival and quality of life. Manual segmentation of brain tumors from CT scan images is a challenging and time consuming task. Size and location accurate detection of brain tumor plays a vital role in the successful diagnosis and treatment of tumors. Brain tumor detection is considered a challenging mission in medical image processing. The aim of this paper is to introduce a scheme for tumor detection in CT scan images using two different techniques Hidden Markov Random Fields (HMRF) and Fuzzy C-means (FCM). The proposed method has been developed in this research in order to construct hybrid method between (HMRF) and threshold. These methods have been applied on 4 different patient data sets. The result of comparison among these methods shows that the proposed method gives good results for brain tissue detection, and is more robust and effective compared with (FCM) techniques.

  11. Remote Postoperative Epidural Hematoma after Brain Tumor Surgery

    PubMed Central

    Chung, Ho-Jung; Park, Jae-Sung; Jeun, Sin-Soo

    2015-01-01

    A postoperative epidural hematoma (EDH) is a serious and embarrassing complication, which usually occurs at the site of operation after intracranial surgery. However, remote EDH is relatively rare. We report three cases of remote EDH after brain tumor surgery. All three cases seemed to have different causes of remote postoperative EDH; however, all patients were managed promptly and showed excellent outcomes. Although the exact mechanism of remote postoperative EDH is unknown, surgeons should be cautious of the speed of lowering intracranial pressure and implement basic procedures to prevent this hazardous complication of brain tumor surgery. PMID:26605271

  12. Notching on Cancer's Door: Notch Signaling in Brain Tumors.

    PubMed

    Teodorczyk, Marcin; Schmidt, Mirko H H

    2014-01-01

    Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4), which are activated by three Delta-like (Dll1/3/4) and two Serrate-like (Jagged1/2) ligands. Further, non-canonical Notch ligands such as epidermal growth factor like protein 7 (EGFL7) have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion, and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ-secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy. PMID:25601901

  13. Novel combined fluorescence/reflectance spectroscopy system for guiding brain tumor resections: hardware considerations

    NASA Astrophysics Data System (ADS)

    Xie, Zhiyuan; Xie, Haiyan; Mousavi, Monirehalsadat; Brydegaard, Mikkel; Axelsson, Johan; Andersson-Engels, Stefan

    2013-11-01

    Glioblastoma multiforme (GBM) has long been known as the most common and aggressive form of brain malignancy. The morphological similarities of the malignant and surrounding tissue cause difficulties to distinct the tumors during surgery. In order to achieve better results in resecting malignant brain tumors, a fiber based optical system which can be used intraoperative is developed in this project. In this context, the system hardware details, system controlling interfaces and laboratory testing results are presented. Based on the results obtained from various tests with tissue-equivalent phantoms, the system is proved to have stable performance, robust structure, and have good linearity as well as high sensitivity to low PpIX concentration under strong ambient light conditions.

  14. Progress on the diagnosis and evaluation of brain tumors

    PubMed Central

    Gao, Huile

    2013-01-01

    Abstract Brain tumors are one of the most challenging disorders encountered, and early and accurate diagnosis is essential for the management and treatment of these tumors. In this article, diagnostic modalities including single-photon emission computed tomography, positron emission tomography, magnetic resonance imaging, and optical imaging are reviewed. We mainly focus on the newly emerging, specific imaging probes, and their potential use in animal models and clinical settings. PMID:24334439

  15. In vivo pink-beam imaging and fast alignment procedure for rat brain tumor radiation therapy.

    PubMed

    Nemoz, Christian; Kibleur, Astrid; Hyacinthe, Jean Noël; Berruyer, Gilles; Brochard, Thierry; Bräuer-Krisch, Elke; Le Duc, Géraldine; Brun, Emmanuel; Elleaume, Hélène; Serduc, Raphaël

    2016-01-01

    A fast positioning method for brain tumor microbeam irradiations for preclinical studies at third-generation X-ray sources is described. The three-dimensional alignment of the animals relative to the X-ray beam was based on the X-ray tomography multi-slices after iodine infusion. This method used pink-beam imaging produced by the ID17 wiggler. A graphical user interface has been developed in order to define the irradiation parameters: field width, height, number of angles and X-ray dose. This study is the first reporting an image guided method for soft tissue synchrotron radiotherapy. It allowed microbeam radiation therapy irradiation fields to be reduced by a factor of ∼20 compared with previous studies. It permitted more targeted, more efficient brain tumor microbeam treatments and reduces normal brain toxicity of the radiation treatment. PMID:26698083

  16. High-resolution brain tumor visualization using three-dimensional x-ray phase contrast tomography.

    PubMed

    Pfeiffer, F; Bunk, O; David, C; Bech, M; Le Duc, G; Bravin, A; Cloetens, P

    2007-12-01

    We report on significant advances and new results concerning a recently developed method for grating-based hard x-ray phase tomography. We demonstrate how the soft tissue sensitivity of the technique is increased and show in vitro tomographic images of a tumor bearing rat brain sample, without use of contrast agents. In particular, we observe that the brain tumor and the white and gray brain matter structure in a rat's cerebellum are clearly resolved. The results are potentially interesting from a clinical point of view, since a similar approach using three transmission gratings can be implemented with more readily available x-ray sources, such as standard x-ray tubes. Moreover, the results open the way to in vivo experiments in the near future. PMID:18029984

  17. Nanoparticle-Mediated Photothermal Therapy of Brain Tumors

    NASA Astrophysics Data System (ADS)

    Makkouk, Amani R.; Madsen, Steen J.

    Nanoparticles (10-1,000 nm diameter) have been investigated for use in numerous diagnostic and therapeutic applications. Gold nanoparticles are particularly appealing due to their biological inertness and the ability to conjugate a wide variety of ligands to their surface. Additionally, their optical properties can be tuned through variations of their size, shape, and composition. For example, gold-silica nanoshells, consisting of a spherical dielectric silica core (100-120 nm diameter) surrounded by a 10-20 nm gold shell, have a strong resonant absorption at approximately 800 nm where light has significant penetration in biological tissues. Following light absorption, surface electrons are photoexcited and the resultant heated electron gas is dissipated to the surrounding medium causing thermal damage. The ability of nanoparticles to convert optical energy to thermal energy makes them ideally suited for photothermal therapy (PTT). This review focuses on the utility of gold-silica nanoshells in PTT of brain tumors. PTT has proven effective in a number of in vitro and in vivo studies. Of particular clinical relevance are results demonstrating PTT efficacy in an orthotopic canine model.

  18. Specific absorbed fractions of energy from internal photon sources in brain tumor and cerebrospinal fluid

    SciTech Connect

    Evans, J.F. )); Stubbs, J.B. )

    1995-03-01

    Transferrin, radiolabeled with In-111, can be coinjected into glioblastoma multiforme lesions, and subsequent scintigraphic imaging can demonstrate the biokinetics of the cytotoxic transferrin. The administration of [sup 111]In transferrin into a brain tumor results in distribution of radioactivity in the brain, brain tumor, and the cerebrospinal fluid (CSF). Information about absorbed radiation doses to these regions, as well as other nearby tissues and organs, is important for evaluating radiation-related risks from this procedure. The radiation dose is usually estimated for a mathematical representation of the human body. We have included source/target regions for the eye, lens of the eye, spinal column, spinal CSF, cranial CSF, and a 100-g tumor within the brain of an adult male phantom developed by Cristy and Eckerman. The spinal column, spinal CSF, and the eyes have not been routinely included in photon transport simulations. Specific absorbed fractions (SAFs) as a function of photon energy were calculated using the ALGAMP computer code, which utilizes Monte Carlo techniques for simulating photon transport. The ALGAMP code was run three times, with the source activity distributed uniformly within the tumor, cranial CSF, and the spinal CSF volumes. These SAFs, which were generated for 12 discrete photon energies ranging from 0.01 to 4.0 MeV, were used with decay scheme data to calculate [ital S]-values needed for estimating absorbed doses. [ital S]-values for [sup 111]In are given for three source regions (brain tumor, cranial CSF, and spinal CSF) and all standard target regions/organs, the eye and lens, as well as to tissues within these source regions. [ital S]-values for the skeletal regions containing active marrow are estimated. These results are useful in evaluating the radiation doses from intracranial administration of [sup 111]In transferrin.

  19. MRI virtual biopsy and treatment of brain metastatic tumors with targeted nanobioconjugates: nanoclinic in the brain.

    PubMed

    Patil, Rameshwar; Ljubimov, Alexander V; Gangalum, Pallavi R; Ding, Hui; Portilla-Arias, Jose; Wagner, Shawn; Inoue, Satoshi; Konda, Bindu; Rekechenetskiy, Arthur; Chesnokova, Alexandra; Markman, Janet L; Ljubimov, Vladimir A; Li, Debiao; Prasad, Ravi S; Black, Keith L; Holler, Eggehard; Ljubimova, Julia Y

    2015-05-26

    Differential diagnosis of brain magnetic resonance imaging (MRI) enhancement(s) remains a significant problem, which may be difficult to resolve without biopsy, which can be often dangerous or even impossible. Such MRI enhancement(s) can result from metastasis of primary tumors such as lung or breast, radiation necrosis, infections, or a new primary brain tumor (glioma, meningioma). Neurological symptoms are often the same on initial presentation. To develop a more precise noninvasive MRI diagnostic method, we have engineered a new class of poly(β-l-malic acid) polymeric nanoimaging agents (NIAs). The NIAs carrying attached MRI tracer are able to pass through the blood-brain barrier (BBB) and specifically target cancer cells for efficient imaging. A qualitative/quantitative "MRI virtual biopsy" method is based on a nanoconjugate carrying MRI contrast agent gadolinium-DOTA and antibodies recognizing tumor-specific markers and extravasating through the BBB. In newly developed double tumor xenogeneic mouse models of brain metastasis this noninvasive method allowed differential diagnosis of HER2- and EGFR-expressing brain tumors. After MRI diagnosis, breast and lung cancer brain metastases were successfully treated with similar tumor-targeted nanoconjugates carrying molecular inhibitors of EGFR or HER2 instead of imaging contrast agent. The treatment resulted in a significant increase in animal survival and markedly reduced immunostaining for several cancer stem cell markers. Novel NIAs could be useful for brain diagnostic MRI in the clinic without currently performed brain biopsies. This technology shows promise for differential MRI diagnosis and treatment of brain metastases and other pathologies when biopsies are difficult to perform. PMID:25906400

  20. American brain tumor patients treated with BNCT in Japan

    SciTech Connect

    Laramore, G.E.; Griffin, B.R.; Spence, A.

    1995-11-01

    The purpose of this work is to establish and maintain a database for patients from the United States who have received BNCT in Japan for malignant gliomas of the brain. This database will serve as a resource for the DOE to aid in decisions relating to BNCT research in the United States, as well as assisting the design and implementation of clinical trials of BNCT for brain cancer patients in this country. The database will also serve as an information resource for patients with brain tumors and their families who are considering this form of therapy.

  1. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts1

    PubMed Central

    Herrmann, Kelsey; Erokwu, Bernadette O.; Johansen, Mette L.; Basilion, James P.; Gulani, Vikas; Griswold, Mark A.; Flask, Chris A.; Brady-Kalnay, Susann M.

    2016-01-01

    Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI) techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents. PMID:27084431

  2. Infrared microspectroscopic imaging of benign breast tumor tissue sections

    NASA Astrophysics Data System (ADS)

    Fabian, H.; Lasch, P.; Boese, M.; Haensch, W.

    2003-12-01

    We have applied infrared microspectroscopic imaging for the examination of benign breast tumor tissue sections. The IR spectra of the sections were obtained by classical point microscopy with a movable stage and via a microscope equipped with a focal plane array detector. The infrared microscopic data were analysed using functional group mapping techniques and cluster analysis. The output values of the two procedures were reassembled into infrared images of the tissues, and were compared with standard staining images of the corresponding tissue region. The comparative examination of identical tissue sections by the two IR approaches enabled us to assess potential problems associated with tissue microheterogeneity. It was found that in case of fibroadenoma, a benign lesion located in breast ducts, point microscopy with a spot size of ˜30 μm is a useful practical approach which minimizes the possibility of 'contamination' of the spectra because of spectral averaging of all tissue components present in the corresponding microareas. A comparison of the spectra of the benign breast tumor with those of a malignant ductal carcinoma in situ revealed that IR microspectroscopy has the potential to differentiate between these two breast tumor types.

  3. CCI-779 in Treating Patients With Soft Tissue Sarcoma or Gastrointestinal Stromal Tumor

    ClinicalTrials.gov

    2013-06-03

    Gastrointestinal Stromal Tumor; Recurrent Adult Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  4. Spectral domain optical coherence tomography for ex vivo brain tumor analysis

    NASA Astrophysics Data System (ADS)

    Lenz, Marcel; Krug, Robin; Jaedicke, Volker; Stroop, Ralf; Schmieder, Kirsten; Hofmann, Martin R.

    2015-07-01

    Non-contact imaging methods to distinguish between healthy tissue and brain tumor tissue during surgery would be highly desirable but are not yet available. Optical Coherence Tomography (OCT) is a non-invasive imaging technology with a resolution around 1-15 μm and a penetration depth of 1-2 mm that may satisfy the demands. To analyze its potential, we measured ex vivo human brain tumor tissue samples from 10 patients with a Spectral Domain OCT system (Thorlabs Callisto: center wavelength of 930 nm) and compared the results with standard histology. In detail, three different measurements were made for each sample. First the sample was measured directly after surgery. Then it was embedded in paraffin (also H and E staining) and examined for the second time. At last, the slices of each paraffin block cut by the pathology were measured. Each time a B-scan was created and for a better comparison with the histology a 3D image was generated, in order to get the corresponding en face images. In both, histopathological diagnosis and the analysis of the OCT images, different types of brain tumor showed difference in structure. This has been affirmed by two blinded investigators. Nevertheless the difference between two images of samples taken directly after surgery is less distinct. To enhance the contrast in the images further, we employ Spectroscopic OCT and pattern recognition algorithms and compare these results to the histopathological standard.

  5. Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models

    NASA Astrophysics Data System (ADS)

    Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

    2014-02-01

    Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

  6. Epigenetics in Brain Tumors: HDACs Take Center Stage

    PubMed Central

    Eyüpoglu, Ilker Y.; Savaskan, Nicolai E.

    2016-01-01

    Primary tumors of the brain account for 2 % of all cancers with malignant gliomas taking the lion’s share at 70 %. Malignant gliomas (high grade gliomas WHO° III and °IV) belong to one of the most threatening tumor entities known for their disappointingly short median survival time of just 14 months despite maximum therapy according to current gold standards. Malignant gliomas manifest various factors, through which they adapt and manipulate the tumor microenvironment to their advantage. Epigenetic mechanisms operate on the tumor microenvironment by de- and methylation processes and imbalances between the histone deacetylases (HDAC) and histone acetylases (HAT). Many compounds have been discovered modulating epigenetically controlled signals. Recent studies indicate that xCT (system xc-, SLC7a11) and CD44 (H-CAM, ECM-III, HUTCH-1) functions as a bridge between these epigenetic regulatory mechanisms and malignant glioma progression. The question that ensues is the extent to which therapeutic intervention on these signaling pathways would exert influence on the treatment of malignant gliomas as well as the extent to which manipulation of HDAC activity can sensitize tumor cells for chemotherapeutics through ‘epigenetic priming’. In light of considering the current stagnation in the development of therapeutic options, the need for new strategies in the treatment of gliomas has never been so pressing. In this context the possibility of pharmacological intervention on tumor-associated genes by epigenetic priming opens a novel path in the treatment of primary brain tumors. PMID:26521944

  7. Brain Tumors - Multiple Languages: MedlinePlus

    MedlinePlus

    ... page, please enable JavaScript. French (français) Japanese (日本語) Korean (한국어) Russian (Русский) Somali (af Soomaali) Spanish (español) ... 脳スキャン検査 - 日本語 (Japanese) Bilingual PDF Health Information Translations Korean (한국어) Brain Scan 뇌 스캔 - 한국어 (Korean) Bilingual ...

  8. II. Perinatal brain tumors: a review of 250 cases.

    PubMed

    Isaacs, Hart

    2002-11-01

    Central nervous system tumors occur considerably less often in the fetus and neonate than in the older child. They are not entirely the same as those present later in life. Their location, biologic behavior, response to therapy, and histologic types are different. Fetal and neonatal brain tumors (n = 250) were collected from the literature and studied for this review. The overall survival rate was 28%. The entire cranial cavity may be filled with tumor, and stillbirth is not uncommon. Macrocephaly was the most frequent presentation regardless of histology. Outcome is related to the size and location of the tumor, the histologic type, surgical resectability, and the condition of the infant at the time of diagnosis. Neonates with choroid plexus papillomas, gangliogliomas, and low-grade astrocytomas have the best prognosis, whereas those with teratomas and primitive neuroectodermal tumors have the worst prognosis. PMID:12504200

  9. A correlative study of clinical-pathologic characteristics of human brain tumors and blood brain barrier (BBB) permeability evaluated with Ga-68 EDTA and positron emission tomography

    SciTech Connect

    Wapenski, J.A.; Hawkins, R.A.; Mazziotta, J.C.; Phelps, M.E.; Huang, S.C.

    1985-05-01

    The authors investigated the relationship between quantitative estimates of BBB permeability and the clinical and pathologic characteristics of human brain tumors. BBB permeability in 12 patients with either primary (4) or metastatic (8) brain tumors were studied with Ga-68 EDTA and PET with a two compartment model. The clinical and pathologic characteristics of the tumors were reviewed retrospectively. PET estimates of the transfer constant K/sub 1/ (ml/min/gm) paralleled the X-ray CT evidence of BBB disruption. Biopsies of four patients provided histologic support for the presumed pathophysiologic mechanism of BBB disruption, in the degree of alteration of brain vascularity and cellular architecture. For example, a patient with a hemorrhagic melanoma and a K/sub 1/ = 0.0049 ml/min/gm had gross hemorrhage, little recognizeable brain tissue and evidence of neovascularization on biopsy.

  10. Measurement of Steroid Concentrations in Brain Tissue: Methodological Considerations

    PubMed Central

    Taves, Matthew D.; Ma, Chunqi; Heimovics, Sarah A.; Saldanha, Colin J.; Soma, Kiran K.

    2011-01-01

    It is well recognized that steroids are synthesized de novo in the brain (neurosteroids). In addition, steroids circulating in the blood enter the brain. Steroids play numerous roles in the brain, such as influencing neural development, adult neuroplasticity, behavior, neuroinflammation, and neurodegenerative diseases such as Alzheimer’s disease. In order to understand the regulation and functions of steroids in the brain, it is important to directly measure steroid concentrations in brain tissue. In this brief review, we discuss methods for the detection and quantification of steroids in the brain. We concisely present the major advantages and disadvantages of different technical approaches at various experimental stages: euthanasia, tissue collection, steroid extraction, steroid separation, and steroid measurement. We discuss, among other topics, the potential effects of anesthesia and saline perfusion prior to tissue collection; microdissection via Palkovits punch; solid phase extraction; chromatographic separation of steroids; and immunoassays and mass spectrometry for steroid quantification, particularly the use of mass spectrometry for “steroid profiling.” Finally, we discuss the interpretation of local steroid concentrations, such as comparing steroid levels in brain tissue with those in the circulation (plasma vs. whole blood samples; total vs. free steroid levels). We also present reference values for a variety of steroids in different brain regions of adult rats. This brief review highlights some of the major methodological considerations at multiple experimental stages and provides a broad framework for designing studies that examine local steroid levels in the brain as well as other steroidogenic tissues, such as thymus, breast, and prostate. PMID:22654806

  11. A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle.

    PubMed

    Kircher, Moritz F; de la Zerda, Adam; Jokerst, Jesse V; Zavaleta, Cristina L; Kempen, Paul J; Mittra, Erik; Pitter, Ken; Huang, Ruimin; Campos, Carl; Habte, Frezghi; Sinclair, Robert; Brennan, Cameron W; Mellinghoff, Ingo K; Holland, Eric C; Gambhir, Sanjiv S

    2012-05-01

    The difficulty in delineating brain tumor margins is a major obstacle in the path toward better outcomes for patients with brain tumors. Current imaging methods are often limited by inadequate sensitivity, specificity and spatial resolution. Here we show that a unique triple-modality magnetic resonance imaging-photoacoustic imaging-Raman imaging nanoparticle (termed here MPR nanoparticle) can accurately help delineate the margins of brain tumors in living mice both preoperatively and intraoperatively. The MPRs were detected by all three modalities with at least a picomolar sensitivity both in vitro and in living mice. Intravenous injection of MPRs into glioblastoma-bearing mice led to MPR accumulation and retention by the tumors, with no MPR accumulation in the surrounding healthy tissue, allowing for a noninvasive tumor delineation using all three modalities through the intact skull. Raman imaging allowed for guidance of intraoperative tumor resection, and a histological correlation validated that Raman imaging was accurately delineating the brain tumor margins. This new triple-modality-nanoparticle approach has promise for enabling more accurate brain tumor imaging and resection. PMID:22504484

  12. A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle

    NASA Astrophysics Data System (ADS)

    de la Zerda, Adam; Kircher, Moritz F.; Jokerst, Jesse V.; Zavaleta, Cristina L.; Kempen, Paul J.; Mittra, Erik; Pitter, Ken; Huang, Ruimin; Campos, Carl; Habte, Frezghi; Sinclair, Robert; Brennan, Cameron W.; Mellinghoff, Ingo K.; Holland, Eric C.; Gambhir, Sanjiv S.

    2013-03-01

    The difficulty in delineating brain tumor margins is a major obstacle in the path toward better outcomes for patients with brain tumors. Current imaging methods are often limited by inadequate sensitivity, specificity and spatial resolution. Here we show that a unique triplemodality magnetic resonance imaging - photoacoustic imaging - Raman imaging nanoparticle (termed here MPR nanoparticles), can accurately help delineate the margins of brain tumors in living mice both preoperatively and intraoperatively. The MPRs were detected by all three modalities with at least a picomolar sensitivity both in vitro and in living mice. Intravenous injection of MPRs into glioblastoma-bearing mice led to MPR accumulation and retention by the tumors, with no MPR accumulation in the surrounding healthy tissue, allowing for a noninvasive tumor delineation using all three modalities through the intact skull. Raman imaging allowed for guidance of intraoperative tumor resection, and a histological correlation validated that Raman imaging was accurately delineating the brain tumor margins. This new triple-modality- nanoparticle approach has promise for enabling more accurate brain tumor imaging and resection.

  13. Photoacoustic monitoring of tumor and normal tissue response to radiation

    PubMed Central

    Rich, Laurie J.; Seshadri, Mukund

    2016-01-01

    Hypoxia is a recognized characteristic of tumors that influences efficacy of radiotherapy (RT). Photoacoustic imaging (PAI) is a relatively new imaging technique that exploits the optical characteristics of hemoglobin to provide information on tissue oxygenation. In the present study, PAI based measures of tumor oxygen saturation (%sO2) were compared to oxygen-enhanced magnetic resonance imaging (MRI) measurements of longitudinal relaxation rate (R1 = 1/T1) and ex-vivo histology in patient derived xenograft (PDX) models of head and neck cancer. PAI was utilized to assess early changes (24 h) in %sO2 following RT and chemoRT (CRT) and to assess changes in salivary gland hemodynamics following radiation. A significant increase in tumor %sO2 and R1 was observed following oxygen inhalation. Good spatial correlation was observed between PAI, MRI and histology. An early increase in %sO2 after RT and CRT detected by PAI was associated with significant tumor growth inhibition. Twenty four hours after RT, PAI also detected loss of hemodynamic response to gustatory stimulation in murine salivary gland tissue suggestive of radiation-induced vascular damage. Our observations illustrate the utility of PAI in detecting tumor and normal tissue hemodynamic response to radiation in head and neck cancers. PMID:26883660

  14. Tumor Engineering: The Other Face of Tissue Engineering

    PubMed Central

    2010-01-01

    Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue. We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of ‘tumor engineering’, that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. PMID:20214448

  15. Analysis of Mammalian Septin Expression in Human Malignant Brain Tumors1

    PubMed Central

    Kim, Dong-Seok; Hubbard, Sherri-Lynn; Peraud, Aurelia; Salhia, Bodour; Sakai, Keiichi; Rutka, James T

    2004-01-01

    Abstract Septins are a highly conserved subfamily of GTPases that play an important role in the process of cytokinesis. To increase our understanding of the expression and localization of the different mammalian septins in human brain tumors, we used antibodies against septins 2, 3, 4, 5, 6, 7, 9, and 11 in immunofluorescence and Western blot analyses of astrocytomas and medulloblastomas. We then characterized the expression and subcellular distribution of the SEPT2 protein in aphidicolin-synchronized U373 MG astrocytoma cells by immunofluorescence and fluorescence-activated cell sorter analysis. To determine the role of SEPT2 in astrocytoma cytokinesis, we inducibly expressed a dominant-negative (DN) SEPT2 mutant in U373 MG astrocytoma cells. We show variable levels and expression patterns of the different septins in brain tissue, brain tumor specimens, and human brain tumor cell lines. SEPT2 was abundantly expressed in all brain tumor samples and cell lines studied. SEPT3 was expressed in medulloblastoma specimens and cell lines, but not in astrocytoma specimens or cell lines. SEPT2 expression was cell cycle-related, with maximal levels in G2-M. Immunocytochemical analysis showed endogenous levels of the different septins within the perinuclear and peripheral cytoplasmic regions. In mitosis, SEPT2 was concentrated at the cleavage furrow. By immunocytochemistry and flow cytometry, we show that a DN SEPT2 mutant inhibits the completion of cell division and results in the accumulation of multinucleated cells. These results suggest that septins are variably expressed in human brain tumors. Stable expression of the DN SEPT2 mutant leads to a G2-M cell cycle block in astrocytoma cells. PMID:15140406

  16. Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

    PubMed Central

    Curtin, James F.; King, Gwendalyn D.; Candolfi, Marianela; Greeno, Remy B.; Kroeger, Kurt M.; Lowenstein, Pedro R.; Castro, Maria G.

    2006-01-01

    Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as ‘immune privileged’, brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another

  17. Life Satisfaction in Adult Survivors of Childhood Brain Tumors

    PubMed Central

    Crom, Deborah B.; Li, Zhenghong; Brinkman, Tara M.; Hudson, Melissa M.; Armstrong, Gregory T.; Neglia, Joseph; Ness, Kirsten K.

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, life-long deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors’ physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggests some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population–based matched controls. Chi-square tests, t-tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors’ general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population. PMID:25027187

  18. Association Between PARP1 Single Nucleotide Polymorphism and Brain Tumors.

    PubMed

    Wang, Hong; Zhang, Kun; Qin, Haifeng; Yang, Lin; Zhang, Liyu; Cao, Yanyan

    2016-05-01

    To systematically evaluate the association between poly(ADP-ribose) polymerase 1 (PARP1) rs1136410 T>C and brain tumor risk, a meta-analysis has been carried out. We performed a meta-analysis of 2004 brain tumor patients and 2944 controls by use of STATA version 12.0 to determine whether the risk of brain tumors was associated with the genotypes or alleles of rs1136410 T>C. We found a significantly decreased risk (ranging from 0.18- to 0.16-fold) in the dominant model (OR = 0.84, 95 % CI = 0.75-0.95), the C vs. T model (OR = 0.82, 95 % CI = 0.74-0.91), and the CT vs. TT model (OR = 0.86, 95 % CI = 0.76-0.98). The same genetic models demonstrated noteworthy associations when analysis was restrained to glioma (OR = 0.85, 95 % CI = 0.75-0.96; OR = 0.83, 95 % CI = 0.74-0.92; OR = 0.87, 95 % CI = 0.76-0.99, respectively). This meta-analysis suggests that PARP1 rs1136410 T>C may play a significant role in the protection against the development of brain tumors and glioma. PMID:25911198

  19. Survival Rates for Selected Childhood Brain and Spinal Cord Tumors

    MedlinePlus

    ... are at best rough estimates. Your child’s doctor knows your child’s situation and is your best source of information on this topic. Last Medical Review: 08/12/2014 Last Revised: 01/21/2016 Back to top » Guide Topics What Is Brain/CNS Tumors In Children? Causes, Risk Factors, and ...

  20. Learning Profiles of Survivors of Pediatric Brain Tumors

    ERIC Educational Resources Information Center

    Barkon, Beverly

    2009-01-01

    By 2010 it is predicted that one in 900 adults will be survivors of some form of pediatric cancer. The numbers are somewhat lower for survivors of brain tumors, though their numbers are increasing. Schools mistakenly believe that these children easily fit pre-existing categories of disability. Though these students share some of the…

  1. Genetic abnormality predicts benefit for a rare brain tumor

    Cancer.gov

    A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion.

  2. Dynamic effects of point source electroporation on the rat brain tissue.

    PubMed

    Sharabi, Shirley; Last, David; Guez, David; Daniels, Dianne; Hjouj, Mohammad Ibrahim; Salomon, Sharona; Maor, Elad; Mardor, Yael

    2014-10-01

    In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r(2)=0.99, p<0.001) and the number of treatment pulses (r(2)=0.94, p<0.002). Blood-brain barrier disruption depicted 3.2±0.3 times larger volumes than the final permanent damage volumes (p<0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors. PMID:24976141

  3. PDT-induced apoptosis in brain tissue in vivo: a retrospective study

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar D.; Portnoy, Michelle; Wilson, Brian C.

    1999-07-01

    The apoptotic response of normal brain and intracranial VX2 tumor following photodynamic therapy mediated by five different photodynamic drugs, Photofrin, ALA, AlClPc, SnET2 and mTHPC, was evaluated in a preliminary retrospective analysis. Rabbit brain, with or without tumor, was treated by PDT with interstitial light delivery. Histological sections at 24 h post PDT were assessed by the TUNEL assay. Confocal fluorescence microscopy was used to determine the total apoptotic cell count and the spatial distribution of apoptotic bodies within the tissue. The data were confirmed qualitatively by light microscopy on adjacent H&E-stained sections. Light-only and drug-only controls produced background levels. The highest apoptotic count was seen with Photofrin. The counts in AlClPc-treated animals were not above the background level, while the other 3 photosensitizers gave intermediate levels. With some, but not all, drugs the spatial distribution of apoptotic bodies correlated well with the light fluence distribution. Apoptosis was seen outside the zone of frank coagulative necrosis. There was not apparent drug-dose dependency at the relatively high doses used here. The retrospective nature of this study did not allow optimization of the treatment parameters. Nevertheless, the findings have potentially significant implications, both for understanding the mechanisms of apoptosis in brain tissue and for improving the clinical use of PDT for treatment of patients with malignant brain tumors.

  4. Tumor Engineering: The Other Face of Tissue Engineering

    SciTech Connect

    Ghajar, Cyrus M; Bissell, Mina J

    2010-03-09

    Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue.We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of 'tumor engineering', that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. In 1993, Vacanti and Langer cast a spotlight on the growing gap between patients in need of organ transplants and the amount of available donor organs; they reaffirmed that tissue engineering could eventually address this problem by 'applying principles of engineering and the life sciences toward the development of biological substitutes. Mortality figures and direct health care costs for cancer patients rival those of patients who experience organ failure. Cancer is the second leading cause of death in the United States (Source: American Cancer Society) and it is estimated that direct medical costs for cancer patients approach $100B yearly in the United States alone (Source: National Cancer Institute). In addition, any promising therapy that emerges from the laboratory costs roughly $1.7B to take from bench to bedside. Whereas we have indeed waged war on cancer, the

  5. Synchrotron supported DEI/KES of a brain tumor in an animal model: The search for a microimaging modality

    NASA Astrophysics Data System (ADS)

    Mannan, K. A.; Schültke, E.; Menk, R. H.; Siu, K.; Pavlov, K.; Kelly, M.; McLoughlin, G.; Beveridge, T.; Tromba, G.; Juurlink, B. H.; Chapman, D.; Rigon, L.; Griebel, R. W.

    2005-08-01

    Glioblastoma multiforme (GBM) is the commonest and most aggressive primary brain tumor in humans. The high rate of tumor recurrence results in a poor prognosis despite multimodality treatment. One reason for high rate of recurrence is the invasive nature of the tumor into the surrounding normal brain tissue or multifocal occurrence at sites remote from that of the primary tumor establishment. Existing imaging demonstrates the primary tumor but fail to show the residual tumor microaggregates left behind following initial treatment. In this study, we employed diffraction-enhanced imaging (DEI) in an attempt to find an imaging modality that will provide visualization of residual disease that is not be apparent on MRI or CT scans.

  6. Tumor bed radiosurgery: an emerging treatment for brain metastases.

    PubMed

    Amsbaugh, Mark J; Boling, Warren; Woo, Shiao

    2015-06-01

    While typically used for treating small intact brain metastases, an increasing body of literature examining tumor bed directed stereotactic radiosurgery (SRS) is emerging. There are now over 1000 published cases treated with this approach, and the first prospective trial was recently published. The ideal sequencing of tumor bed SRS is unclear. Current approaches include, a neoadjuvant treatment before resection, alone as an adjuvant after resection, and following surgery combined with whole brain radiotherapy either as an adjuvant or salvage treatment. Based on available evidence, adjuvant stereotactic radiosurgery improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated. While results from published series vary, heterogeneity in both patient populations and methods of reporting results make comparisons difficult. Additional prospective data, including randomized trials are needed to confirm equivalent outcomes to the current standard of care. We review the current literature, identify areas of ongoing contention, and highlight ongoing studies. PMID:25911296

  7. Multi-fractal detrended texture feature for brain tumor classification

    NASA Astrophysics Data System (ADS)

    Reza, Syed M. S.; Mays, Randall; Iftekharuddin, Khan M.

    2015-03-01

    We propose a novel non-invasive brain tumor type classification using Multi-fractal Detrended Fluctuation Analysis (MFDFA) [1] in structural magnetic resonance (MR) images. This preliminary work investigates the efficacy of the MFDFA features along with our novel texture feature known as multifractional Brownian motion (mBm) [2] in classifying (grading) brain tumors as High Grade (HG) and Low Grade (LG). Based on prior performance, Random Forest (RF) [3] is employed for tumor grading using two different datasets such as BRATS-2013 [4] and BRATS-2014 [5]. Quantitative scores such as precision, recall, accuracy are obtained using the confusion matrix. On an average 90% precision and 85% recall from the inter-dataset cross-validation confirm the efficacy of the proposed method.

  8. Interstitial hyperthermia of experimental brain tumor using implant heating system.

    PubMed

    Kobayashi, T; Tanaka, T; Kida, Y; Matsui, M; Ikeda, T

    1989-07-01

    New experimental system of induction hyperthermia for brain tumor using ferromagnetic implant with low Curie point has been developed. The metal implant is cylindrical needle and made of Fe-Pt alloy with low Curie point suitable for hyperthermia (50-60 degrees C). Induction coil and generator which produce maximum power of 200W and variable frequency of 100-500kHz, yielding magnetic power of 16.7Oe, have been developed. Interstitial hyperthermia was made on rat brain tumor model (T9 gliosarcoma) by this system. Significant effects of single hyperthermia (45 degrees C for 30 minutes) were observed by the extension of life span and morphological changes of the tumor. PMID:2778493

  9. Classification of brain tumors using MRI and MRS data

    NASA Astrophysics Data System (ADS)

    Wang, Qiang; Liacouras, Eirini Karamani; Miranda, Erickson; Kanamalla, Uday S.; Megalooikonomou, Vasileios

    2007-03-01

    We study the problem of classifying brain tumors as benign or malignant using information from magnetic resonance (MR) imaging and magnetic resonance spectroscopy (MRS) to assist in clinical diagnosis. The proposed approach consists of several steps including segmentation, feature extraction, feature selection, and classification model construction. Using an automated segmentation technique based on fuzzy connectedness we accurately outline the tumor mass boundaries in the MR images so that further analysis concentrates on these regions of interest (ROIs). We then apply a concentric circle technique on the ROIs to extract features that are utilized by the classification algorithms. To remove redundant features, we perform feature selection where only those features with discriminatory information (among classes) are used in the model building process. The involvement of MRS features further improves the classification accuracy of the model. Experimental results demonstrate the effectiveness of the proposed approach in classifying brain tumors in MR images.

  10. Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery

    NASA Astrophysics Data System (ADS)

    Spinelli, Antonello Enrico; Schiariti, Marco P.; Grana, Chiara M.; Ferrari, Mahila; Cremonesi, Marta; Boschi, Federico

    2016-05-01

    We presented the first example of Cerenkov luminescence imaging (CLI) and radioluminescence imaging (RLI) of human tumor specimens. A patient with a brain meningioma localized in the left parietal region was injected with 166 MBq of Y90-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory. The system is based on a cooled electron multiplied charge coupled device coupled with an f/0.95 17-mm C-mount lens. We showed for the first time the possibility of obtaining CLI and RLI images of fresh human brain tumor specimens removed during neurosurgery.

  11. Interleukin-1β induces the upregulation of caveolin-1 expression in a rat brain tumor model

    PubMed Central

    QIN, LI-JUAN; JIA, YONG-SEN; ZHANG, YI-BING; WANG, YIN-HUAN

    2016-01-01

    The aim of the present study was to investigate the expression of caveolin-1 in rat brain glioma tissue, and to determine whether interleukin-1β (IL-1β) has a role in this process. Using glioma cells, a tumor-burdened rat model was established, and the expression of caveolin-1 protein in the tumor sites was significantly increased following intracarotid infusion of IL-1β (3.7 ng/kg/min), as indicated by western blot analysis. The maximum value of the caveolin-1 expression was observed in tumor-burdened rats after 60 min of IL-1β perfusion, and which was significantly enhanced by vascular endothelial growth factor (VEGF). In addition, VEGF also significantly increased IL-1β-induced blood tumor barrier (BTB) permeability. The results suggest that the IL-1β-induced BTB permeability increase may be associated with the expression of caveolin-1 protein, and VEGF may be involved in this process. PMID:27073627

  12. A dose comparison of proton radiotherapy and photon radiotherapy for pediatric brain tumor

    NASA Astrophysics Data System (ADS)

    Kim, S. Y.; Cho, J. H.

    2014-12-01

    The purpose of this study was to investigate the effectiveness of photon radiotherapy and to compare the dose of treatment planning between proton radiotherapy and 3D conformal radiation therapy (3D-CRT) for pediatric brain tumor patients. This study was conducted in five pediatric brain tumor patients who underwent craniospinal irradiation treatment from October 2013 to April 2014 in the hospital. The study compared organs at risk (OARs) by assessing the dose distribution of normal tissue from the proton plan and 3D-CRT. Furthermore, this study assessed the treatment plans by looking at the homogeneity index (HI) and conformity index (CI). As a result, the study revealed OARs due to the small volume proton radiotherapy dose distribution in the normal tissue. Also, by comparing HI and CI between the 3D-CRT and proton radiotherapy plan, the study found that the dose of proton radiotherapy plan was homogenized. When conducting 3D-CRT and proton radiotherapy in a dose-volume histogram comparison, the dose of distribution turned out to be low. Consequently, proton radiotherapy is used for protecting the normal tissue, and is used in tumor tissue as a homogenized dose for effective treatment.

  13. Computer aided detection of tumor and edema in brain FLAIR magnetic resonance image using ANN

    NASA Astrophysics Data System (ADS)

    Pradhan, Nandita; Sinha, A. K.

    2008-03-01

    This paper presents an efficient region based segmentation technique for detecting pathological tissues (Tumor & Edema) of brain using fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. This work segments FLAIR brain images for normal and pathological tissues based on statistical features and wavelet transform coefficients using k-means algorithm. The image is divided into small blocks of 4×4 pixels. The k-means algorithm is used to cluster the image based on the feature vectors of blocks forming different classes representing different regions in the whole image. With the knowledge of the feature vectors of different segmented regions, supervised technique is used to train Artificial Neural Network using fuzzy back propagation algorithm (FBPA). Segmentation for detecting healthy tissues and tumors has been reported by several researchers by using conventional MRI sequences like T1, T2 and PD weighted sequences. This work successfully presents segmentation of healthy and pathological tissues (both Tumors and Edema) using FLAIR images. At the end pseudo coloring of segmented and classified regions are done for better human visualization.

  14. Dermatofibrosarcoma Protuberans: Insights into a Rare Soft Tissue Tumor

    PubMed Central

    Al Barwani, Aliya Sarhan; Taif, Sawsan; Al Mazrouai, Reem Ahmed; Al Muzahmi, Khamis Salim; Alrawi, Asif

    2016-01-01

    Dermatofibrosarcoma protuberans (DFSP) is a rare soft tumor which originally represents a cutaneous sarcoma. It grows slowly and presents usually as nodular superficial lesion on the trunk or the extremities. Although these tumors are locally aggressive with high rate of recurrence following surgery; the prognosis is considered excellent when it is effectively treated. The radiological appearance of this tumor has rarely been studied and findings infrequently discussed in the literature probably because many lesions underwent resection before imaging. Although imaging is infrequently performed for this lesion; it can show characteristic features and demonstrate the full extent. Imaging may also play a role in the differentiation of this tumor from more serious soft tissue lesions such as more aggressive sarcomas and hemangioma. In this article, we discuss the imaging findings of DFSP that can aid in its diagnosis and its variable appearances. In addition; the clinical presentation and treatment options are also described with review of the previous literature. PMID:27195182

  15. One-dimensional phosphorus-31 chemical shift imaging of human brain tumors

    SciTech Connect

    Rutter, A.; Hugenholtz, H.; Saunders, J.K.

    1995-06-01

    Phosphorus magnetic resonance spectroscopy has been used noninvasively to determine characteristic spectral parameters for untreated human brain tumors as a prelude to its use in clinical diagnosis. The spectra, which reflect the relative amounts of phosphorus-containing compounds, and the pH within and surrounding the tumors, were obtained in vivo using the the localization technique of one-dimensional chemical shift imaging applied with a surface coil. Phosphorus-31 chemical shift imaging was performed successfully in vivo on 9 volunteers and 27 patients with untreated brain tumors, including 7 with astrocytoma, 4 with glioblastoma, 3 with meningioma, and 11 with metastases. This study provides spectra from within and surrounding the brain tumors, and allows accountability for the heterogeneity of brain tumors by the selection of the maximum data point for each parameter. The ratios of resonance areas, phosphodiesters over nucleoside triphosphate (NTP), and phosphomonoesters over NTP, were found to be higher in glioblastomas (2.55 {plus_minus} 0.22, 1.06 {plus_minus} 0.09) and astorcytomas (3.04 {plus_minus} 0.36, 1.28 {plus_minus} 0.36) than in normal brain (2.00 {plus_minus} 0.32, 0.79 {plus_minus}0.22). The ratios of areas due to inorganic phosphate and NTP, and phosphocreatine and NTP, also were higher in astrocytomas (1.16 {plus_minus} 0.40, 1.17 {plus_minus} 0.41) compared with glioblastomas (0.68 {plus_minus} 0.01, 0.88 {plus_minus} 0.19) and normal brain (0.61 {plus_minus}0.03, 0.77 {plus_minus} 0.03). The pH of brain tumors ranged from alkaline to neutral, with meningiomas consistently having alkaline pH. These data show that there are statistically significant differences in the magnetic resonance parameters of the affected brain hemispheres of patients with astrocytomas, glioblastomas, meningiomas, and normal brain tissue, and underline the need for a multisite clinical trial to establish clinical criteria for diagnosis. 28 refs., 3 figs., 2 tabs.

  16. Hierarchical non-negative matrix factorization to characterize brain tumor heterogeneity using multi-parametric MRI.

    PubMed

    Sauwen, Nicolas; Sima, Diana M; Van Cauter, Sofie; Veraart, Jelle; Leemans, Alexander; Maes, Frederik; Himmelreich, Uwe; Van Huffel, Sabine

    2015-12-01

    Tissue characterization in brain tumors and, in particular, in high-grade gliomas is challenging as a result of the co-existence of several intra-tumoral tissue types within the same region and the high spatial heterogeneity. This study presents a method for the detection of the relevant tumor substructures (i.e. viable tumor, necrosis and edema), which could be of added value for the diagnosis, treatment planning and follow-up of individual patients. Twenty-four patients with glioma [10 low-grade gliomas (LGGs), 14 high-grade gliomas (HGGs)] underwent a multi-parametric MRI (MP-MRI) scheme, including conventional MRI (cMRI), perfusion-weighted imaging (PWI), diffusion kurtosis imaging (DKI) and short-TE (1)H MRSI. MP-MRI parameters were derived: T2, T1 + contrast, fluid-attenuated inversion recovery (FLAIR), relative cerebral blood volume (rCBV), mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and the principal metabolites lipids (Lip), lactate (Lac), N-acetyl-aspartate (NAA), total choline (Cho), etc. Hierarchical non-negative matrix factorization (hNMF) was applied to the MP-MRI parameters, providing tissue characterization on a patient-by-patient and voxel-by-voxel basis. Tissue-specific patterns were obtained and the spatial distribution of each tissue type was visualized by means of abundance maps. Dice scores were calculated by comparing tissue segmentation derived from hNMF with the manual segmentation by a radiologist. Correlation coefficients were calculated between each pathologic tissue source and the average feature vector within the corresponding tissue region. For the patients with HGG, mean Dice scores of 78%, 85% and 83% were obtained for viable tumor, the tumor core and the complete tumor region. The mean correlation coefficients were 0.91 for tumor, 0.97 for necrosis and 0.96 for edema. For the patients with LGG, a mean Dice score of 85% and mean correlation coefficient of 0.95 were found for the tumor region. hNMF was

  17. Evaluation of endogenous species involved in brain tumors using multiphoton photoacoustic spectroscopy

    NASA Astrophysics Data System (ADS)

    Dahal, Sudhir; Cullum, Brian M.

    2013-05-01

    It has been shown that using non-resonant multiphoton photoacoustic spectroscopy (NMPPAS), excised brain tumor (grade III astrocytoma) and healthy tissue can be differentiated from each other, even in neighboring biopsy samples[1, 2]. Because of this, this powerful technique offers a great deal of potential for use as a surgical guidance technique for tumor margining with up to cellular level spatial resolution[3]. NMPPAS spectra are obtained by monitoring the non-radiative relaxation pathways via ultrasonic detection, following two-photon excitation with light in the optical diagnostic window (740nm-1100nm). Based upon significant differences in the ratiometric absorption of the tissues following 970nm and 1100nm excitation, a clear classification of the tissue can be made. These differences are the result of variations in composition and oxidation state of certain endogenous biochemical species between healthy and malignant tissues. In this work, NADH, NAD+ and ATP were measured using NMPPAS in model gelatin tissue phantoms to begin to understand which species might be responsible for the observed spectral differences in the tissue. Each species was placed in specific pH environments to provide control over the ratio of oxidized to reduced forms of the species. Ratiometric analyses were then conducted to account for variability caused due to instrumental parameters. This paper will discuss the potential roles of each of the species for tumor determination and their contribution to the spectral signature.

  18. Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

    NASA Astrophysics Data System (ADS)

    Rendon, Cesar A.; Lilge, Lothar

    2004-10-01

    In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

  19. Characterisation and modelling of brain tissue for surgical simulation.

    PubMed

    Mendizabal, A; Aguinaga, I; Sánchez, E

    2015-05-01

    Interactive surgical simulators capable of providing a realistic visual and haptic feedback to users are a promising technology for medical training and surgery planification. However, modelling the physical behaviour of human organs and tissues for surgery simulation remains a challenge. On the one hand, this is due to the difficulty to characterise the physical properties of biological soft tissues. On the other hand, the challenge still remains in the computation time requirements of real-time simulation required in interactive systems. Real-time surgical simulation and medical training must employ a sufficiently accurate and simple model of soft tissues in order to provide a realistic haptic and visual response. This study attempts to characterise the brain tissue at similar conditions to those that take place on surgical procedures. With this aim, porcine brain tissue is characterised, as a surrogate of human brain, on a rotational rheometer at low strain rates and large strains. In order to model the brain tissue with an adequate level of accuracy and simplicity, linear elastic, hyperelastic and quasi-linear viscoelastic models are defined. These models are simulated using the ABAQUS finite element platform and compared with the obtained experimental data. PMID:25676499

  20. Human and rat glioma growth, invasion, and vascularization in a novel chick embryo brain tumor model.

    PubMed

    Cretu, Alexandra; Fotos, Joseph S; Little, Brian W; Galileo, Deni S

    2005-01-01

    The mechanisms that control the insidiously invasive nature of malignant gliomas are poorly understood, and their study would be facilitated by an in vivo model that is easy to manipulate and inexpensive. The developing chick embryo brain was assessed as a new xenograft model for the production, growth, and study of human and rat glioma cell lines. Three established glioma lines (U-87 MG, C6, and 9L) were injected into chick embryo brain ventricles on embryonic day (E) 5 and brains were examined after several days to two weeks after injection. All glioma lines survived, produced vascularized intraventricular tumors, and invaded the brain in a manner similar to that in rodents. Rat C6 glioma cells spread along vasculature and also invaded the neural tissue. Human U-87 glioma cells migrated along vasculature and exhibited slight invasion of neural tissue. Rat 9L gliosarcoma cells were highly motile, but migrated only along the vasculature. A derivative of 9L cells that stably expressed the cell surface adhesion molecule NgCAM/L1 was produced and also injected into chick embryo brain ventricles to see if this protein could facilitate tumor cell migration away from the vasculature into areas such as axonal tracts. 9L/NgCAM cells, however, did not migrate away from the vasculature and, thus, this protein alone cannot be responsible for diffuse invasiveness of some gliomas. 9L/NgCAM cell motility was assessed in vitro using sophisticated time-lapse microscopy and quantitative analysis, and was significantly altered compared to parental 9L cells. These studies demonstrate that the chick embryo brain is a successful and novel xenograft model for mammalian gliomas and demonstrate the potential usefulness of this new model for studying glioma tumor cell growth, vascularization, and invasiveness. PMID:16158250

  1. Postictal Magnetic Resonance Imaging Changes Masquerading as Brain Tumor Progression: A Case Series

    PubMed Central

    Dunn-Pirio, Anastasie M.; Billakota, Santoshi; Peters, Katherine B.

    2016-01-01

    Seizures are common among patients with brain tumors. Transient, postictal magnetic resonance imaging abnormalities are a long recognized phenomenon. However, these radiographic changes are not as well studied in the brain tumor population. Moreover, reversible neuroimaging abnormalities following seizure activity may be misinterpreted for tumor progression and could consequently result in unnecessary tumor-directed treatment. Here, we describe two cases of patients with brain tumors who developed peri-ictal pseudoprogression and review the relevant literature. PMID:27462237

  2. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

    PubMed Central

    Sarin, Hemant; Kanevsky, Ariel S; Wu, Haitao; Brimacombe, Kyle R; Fung, Steve H; Sousa, Alioscka A; Auh, Sungyoung; Wilson, Colin M; Sharma, Kamal; Aronova, Maria A; Leapman, Richard D; Griffiths, Gary L; Hall, Matthew D

    2008-01-01

    Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives. PMID:19094226

  3. Nanoparticle mediated silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation

    PubMed Central

    Kievit, Forrest M.; Stephen, Zachary R.; Wang, Kui; Dayringer, Christopher J.; Sham, Jonathan G.; Ellenbogen, Richard G.; Silber, John R.; Zhang, Miqin

    2015-01-01

    Medulloblastoma (MB) and ependymoma (EP) are the most common pediatric brain tumors, afflicting 3,000 children annually. Radiotherapy (RT) is an integral component in the treatment of these tumors; however, the improvement in survival is often accompanied by radiation-induced adverse developmental and psychosocial sequelae. Therefore, there is an urgent need to develop strategies that can increase the sensitivity of brain tumors cells to RT while sparing adjacent healthy brain tissue. Apurinic endonuclease 1 (Ape1), an enzyme in the base excision repair pathway, has been implicated in radiation resistance in cancer. Pharmacological and specificity limitations inherent to small molecule inhibitors of Ape1 have hindered their clinical development. Here we report on a nanoparticle (NP) based siRNA delivery vehicle for knocking down Ape1 expression and sensitizing pediatric brain tumor cells to RT. The NP comprises a superparamagnetic iron oxide core coated with a biocompatible, biodegradable coating of chitosan, polyethylene glycol (PEG), and polyethyleneimine (PEI) that is able to bind and protect siRNA from degradation and to deliver siRNA to the perinuclear region of target cells. NPs loaded with siRNA against Ape1 (NP:siApe1) knocked down Ape1 expression over 75% in MB and EP cells, and reduced Ape1 activity by 80%. This reduction in Ape1 activity correlated with increased DNA damage post-irradiation, which resulted in decreased cell survival in clonogenic assays. The sensitization was specific to therapies generating abasic lesions as evidenced by NP:siRNA not increasing sensitivity to paclitaxel, a microtubule disrupting agent. Our results indicate NP-mediated delivery of siApe1 is a promising strategy for circumventing pediatric brain tumor resistance to RT. PMID:25681012

  4. Imaging and Analytical Methods as Applied to the Evaluation of Vasculature and Hypoxia in Human Brain Tumors

    PubMed Central

    Evans, Sydney M.; Jenkins, Kevin W.; Jenkins, W. Timothy; Dilling, Thomas; Judy, Kevin D.; Schrlau, Amy; Judkins, Alexander; Hahn, Stephen M.; Koch, Cameron J.

    2008-01-01

    Tissue hypoxia results from the interaction of cellular respiration, vascular oxygen carrying capacity, and vessel distribution. We studied the relationship between tumor vasculature and regions of low pO2 using quantitative analysis of binding of the 2-nitroimidazole EF5 given to patients intravenously (21 mg/kg) approximately 24 h preceding surgery. We describe new computer algorithms for determining EF5 binding as a function of radial distance from individual blood vessels and converting this value to tissue pO2. Tissues from six human brain tumors were assessed. In a hemangiopericytoma, a WHO Grade 2 and WHO Grade 3 glial brain tumor, all tissue pO2 values calculated by EF5 binding were >20 mmHg (described as “physiologically oxygenated”). In these three tumors, EF5 binding gradients (measured as a function of distance from each observed vessel) were low, with small positive and negative values averaging close to zero. Much lower tissue oxygen levels were found, including near some vessels, in glioblastomas. Gradients of EF5 binding away from vessels were larger in glioblastomas than in the low-grade tumors, but positive and negative values again averaged to near zero. Based on these preliminary data, we hypothesize a new paradigm for tumor blood flow in human brain tumors whereby in-flowing and out-flowing blood patterns may have contrasting effects on average tissue EF5 (and by inference, oxygen) gradients. Our studies also imply that neither distance to the nearest blood vessel nor distance from each observed blood vessel provide reliable estimates of tissue pO2. PMID:19138031

  5. High incidence of TERT mutation in brain tumor cell lines.

    PubMed

    Johanns, Tanner M; Fu, Yujie; Kobayashi, Dale K; Mei, Yu; Dunn, Ian F; Mao, Diane D; Kim, Albert H; Dunn, Gavin P

    2016-07-01

    TERT promoter gene mutations are highly recurrent in malignant glioma. However, little information exists regarding their presence in experimental brain tumor models. To better characterize systems in which TERT mutation studies could be appropriately modeled experimentally, the TERT promoter was examined by conventional sequencing in primary brain tumor initiating cells (BTIC), two matched recurrent BTIC lines, a panel of established malignant glioma cell lines, and two meningioma cell lines. Telomerase gene expression was examined by quantitative PCR. We found that all glioblastoma BTIC lines harbored a TERT mutation, which was retained in two patient-matched recurrent BTIC. The TERT C228T or C250T mutation was found in 33/35 (94 %) of established malignant glioma cell lines and both meningioma cell lines examined. Brain tumor cell lines expressed variably high telomerase levels. Thus, a high percentage of glioma cell lines, as well as two meningioma cell lines, harbors TERT mutations. These data characterize tractable, accessible models with which to further explore telomerase biology in these tumor types. PMID:26960334

  6. Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors.

    PubMed

    Astrakas, Loukas G; Zurakowski, David; Tzika, A Aria; Zarifi, Maria K; Anthony, Douglas C; De Girolami, Umberto; Tarbell, Nancy J; Black, Peter McLaren

    2004-12-15

    The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors. We evaluate the proton magnetic resonance spectroscopic imaging exams for 66 children with brain tumors. The intracellular biomarkers for choline-containing compounds (Cho), N-acetylaspartate, total creatine, and lipids and/or lactate were measured at the highest Cho region and normalized to the surrounding healthy tissue total creatine. Neuropathological grading was done with WHO criteria. Normalized Cho and lipids and/or lactate were elevated in high-grade (n = 23) versus low-grade (n = 43) tumors, which multiple logistic regression confirmed are independent predictors of tumor grade (for Cho, odds ratio 24.8, P < 0.001; and for lipids and/or lactate, odds ratio 4.4, P < 0.001). A linear combination of normalized Cho and lipids and/or lactate that maximizes diagnostic accuracy was calculated by maximizing the area under the receiver operating characteristic curve. Proton magnetic resonance spectroscopic imaging, although not a proxy for histology, provides noninvasive, in vivo biomarkers for predicting clinical grades of pediatric brain tumors. PMID:15623597

  7. Three-dimensional assessment of brain tissue morphology

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Germann, Marco; Jeanmonod, Daniel; Morel, Anne

    2006-08-01

    The microstructure of brain tissues becomes visible using different types of optical microscopy after the tissue sectioning. This preparation procedure introduces stress and strain in the anisotropic and inhomogeneous soft tissue slices, which are several 10 μm thick. Consequently, the three-dimensional dataset, generated out of the two-dimensional images with lateral submicrometer resolution, needs algorithms to correct the deformations, which can be significant for mellow tissue such as brain segments. The spatial resolution perpendicular to the slices is much worse with respect to the lateral sub-micrometer resolution. Therefore, we propose as complementary method the synchrotron-radiation-based micro computed tomography (SRμCT), which avoids any kind of preparation artifacts due to sectioning and histological processing and yields true micrometer resolution in the three orthogonal directions. The visualization of soft matter by the use of SRμCT, however, is often based on elaborate staining protocols, since the tissue exhibits (almost) the same x-ray absorption as the surrounding medium. Therefore, it is unexpected that human tissue from the pons and the medulla oblongata in phosphate buffer show several features such as the blood vessels and the inferior olivary nucleus without staining. The value of these tomograms lies especially in the precise non-rigid registration of the different sets of histological slices. Applications of this method to larger pieces of brain tissue, such as the human thalamus are planned in the context of stereotactic functional neurosurgery.

  8. Permanent and removable implants for the brachytherapy of brain tumors

    SciTech Connect

    Gutin, P.H.; Phillips, T.L.; Hosobuchi, Y.

    1981-10-01

    Thirty-seven patients harboring primary or metastatic brain tumors were treated with 40 implantations of radioactive sources (/sup 192/Ir, /sup 198/Au, or /sup 125/I) using stereotactic neurosurgical techniques. Most tumors had recurred after surgery, whole brain irradiation, and treatment with all feasible chemotherapeutic agents. Sixteen of the 40 implants were pregnant; 24 were mounted in plastic catheters for removal after the desired dose had been delivered. One or more sources were placed in each tumor to deliver 3500-7350 rad to the tumor's periphery for /sup 198/Au, 4,000-12,000 rad for /sup 192/Ir, and 3,000-20,000 rad for /sup 125/I. Three of the six patients treated with /sup 192/Ir had objective responses for 2, 4, and 12 months, and two stabilized for 8 and 11 months. Seven of the 11 patients treated with /sup 198/Au were evaluable: three responded for 3, 5, and 37 + months, one deteriorating patient with a recurrent tumor stabilized for 6 months, and two deteriorated despite treatment. One patient received an interstitial ''boost'' dose with /sup 198/Au after whole brain irradiation and stabilized for 15 months before developing spinal metastases. Six patients received permanent implants with low activity /sup 125/I. Three of these patients had blioblastomas or anaplastic astrocytomas; all continued to deteriorate despite the interstitial irradiation, presumably because the dose rat was too low. One patient with a low-grade astrocytoma (optic chiasm) responded dramatically to permanent, low activity /sup 125/I implants (11 + months). Another (hypothalamic glioma) had a permanent /sup 125/I implant, responded, as was stable at 9 months when external irradiation was administered. One patient with a suprasellar ''teratoid'' tumor stabilized for 10 months.

  9. Histogram analysis of ADC in brain tumor patients

    NASA Astrophysics Data System (ADS)

    Banerjee, Debrup; Wang, Jihong; Li, Jiang

    2011-03-01

    At various stage of progression, most brain tumors are not homogenous. In this presentation, we retrospectively studied the distribution of ADC values inside tumor volume during the course of tumor treatment and progression for a selective group of patients who underwent an anti-VEGF trial. Complete MRI studies were obtained for this selected group of patients including pre- and multiple follow-up, post-treatment imaging studies. In each MRI imaging study, multiple scan series were obtained as a standard protocol which includes T1, T2, T1-post contrast, FLAIR and DTI derived images (ADC, FA etc.) for each visit. All scan series (T1, T2, FLAIR, post-contrast T1) were registered to the corresponding DTI scan at patient's first visit. Conventionally, hyper-intensity regions on T1-post contrast images are believed to represent the core tumor region while regions highlighted by FLAIR may overestimate tumor size. Thus we annotated tumor regions on the T1-post contrast scans and ADC intensity values for pixels were extracted inside tumor regions as defined on T1-post scans. We fit a mixture Gaussian (MG) model for the extracted pixels using the Expectation-Maximization (EM) algorithm, which produced a set of parameters (mean, various and mixture coefficients) for the MG model. This procedure was performed for each visits resulting in a series of GM parameters. We studied the parameters fitted for ADC and see if they can be used as indicators for tumor progression. Additionally, we studied the ADC characteristics in the peri-tumoral region as identified by hyper-intensity on FLAIR scans. The results show that ADC histogram analysis of the tumor region supports the two compartment model that suggests the low ADC value subregion corresponding to densely packed cancer cell while the higher ADC value region corresponding to a mixture of viable and necrotic cells with superimposed edema. Careful studies of the composition and relative volume of the two compartments in tumor

  10. Measuring the local electrical conductivity of human brain tissue

    NASA Astrophysics Data System (ADS)

    Akhtari, M.; Emin, D.; Ellingson, B. M.; Woodworth, D.; Frew, A.; Mathern, G. W.

    2016-02-01

    The electrical conductivities of freshly excised brain tissues from 24 patients were measured. The diffusion-MRI of the hydrogen nuclei of water molecules from regions that were subsequently excised was also measured. Analysis of these measurements indicates that differences between samples' conductivities are primarily due to differences of their densities of solvated sodium cations. Concomitantly, the sample-to-sample variations of their diffusion constants are relatively small. This finding suggests that non-invasive in-vivo measurements of brain tissues' local sodium-cation density can be utilized to estimate its local electrical conductivity.

  11. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer

    PubMed Central

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G. William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand–receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma. PMID:26322020

  12. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer.

    PubMed

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand-receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma. PMID:26322020

  13. Determining methylation status of methylguanine DNA methyl transferase (MGMT) from formalin-fixed, paraffin embedded tumor tissue

    PubMed Central

    de Abreu, Francine B.; Gallagher, Torrey L.; Liu, Emmeline Z.; Tsongalis, Gregory J.

    2014-01-01

    O-6-methylguanine-DNA methyltransferase (MGMT) has been associated with resistance to alkylating agent cancer therapy in Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults. Lower expression or silencing of the MGMT protein by promoter methylation has been reported to improve survival in patients with GBM [1]. This protocol describes bisulfite conversion, methylation sensitive PCR amplification and data analysis/interpretation. This protocol differs from published protocols in that it:•Describes a detailed method to measure MGMT using DNA extracted from solid tumor tissue. We have optimized the DNA extraction by using FFPE tissue blocks that contain greater than 50% tumor tissue, when non-tumor tissue was also present. Performance of this assay is compromised when lower quantities of tumor cells are used as the methylation status of tumor cells is diluted out by methylation status of normal cells.•The measurement of MGMT could be further (enhanced) optimized using a percentage of methylation ration cutoff of 2 as methylated.•The machine specifications detailed here are specific to measuring MGMT from PPFE tumor tissue. PMID:26150933

  14. Pediatric Brain Tumors: Current Knowledge and Therapeutic Opportunities.

    PubMed

    Glod, John; Rahme, Gilbert J; Kaur, Harpreet; H Raabe, Eric; Hwang, Eugene I; Israel, Mark A

    2016-05-01

    Great progress has been made in many areas of pediatric oncology. However, tumors of the central nervous system (CNS) remain a significant challenge. A recent explosion of data has led to an opportunity to understand better the molecular basis of these diseases and is already providing a foundation for the pursuit of rationally chosen therapeutics targeting relevant molecular pathways. The molecular biology of pediatric brain tumors is shifting from a singular focus on basic scientific discovery to a platform upon which insights are being translated into therapies. PMID:26989915

  15. Brain tumor evaluation using /sup 82/Rb and positron emission tomography

    SciTech Connect

    Yen, C.K.; Yano, Y.; Budinger, T.F.; Friedland, R.P.; Derenzo, S.E.; Huesman, R.H.; O'Brien, H.A.

    1982-06-01

    Positron emission tomography of the brain with 75-sec rubidium-82 obtained from a portable generator (25-day /sup 82/Sr leads to /sup 82/Rb) was used to evaluate the integrity of the blood-brain barrier (BBB) in patients with brain tumors. Rubidium is normally excluded from the central nervous system by the intact BBB, but when the BBB is disrupted by a tumor. Rb enters and pools in the extravascular spaces of the central nervous system. Since Rb is also rapidly cleared from the blood, a high tissue-to-blood ratio of the /sup 82/Rb tracer is achieved in regions of BBB disruption after intravenous injection. With dynamic positron emission tomographic imaging, the extravasation of the Rb tracer can be evaluated independent of the intravascular Rb concentration, and very small changes in the BBB permeability can be detected. The results of our studies in eight patients show that this technique is a promising method for evaluation of the BBB integrity in brain-tumor patients.

  16. Optical Imaging of Targeted β-Galactosidase in Brain Tumors to Detect EGFR Levels

    PubMed Central

    Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

    2015-01-01

    A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging. PMID:25775241

  17. Integrated proteomic platforms for the comparative characterization of medulloblastoma and pilocytic astrocytoma pediatric brain tumors: a preliminary study.

    PubMed

    Martelli, Claudia; Iavarone, Federica; D'Angelo, Luca; Arba, Morena; Vincenzoni, Federica; Inserra, Ilaria; Delfino, Daniela; Rossetti, Diana Valeria; Caretto, Marta; Massimi, Luca; Tamburrini, Gianpiero; Di Rocco, Concezio; Caldarelli, Massimo; Messana, Irene; Castagnola, Massimo; Sanna, Maria Teresa; Desiderio, Claudia

    2015-06-01

    A top-down/bottom-up integrated proteomic approach based on LC-MS and 2-DE analysis was applied for comparative characterization of medulloblastoma and pilocytic astrocytoma posterior cranial fossa pediatric brain tumor tissues. Although rare, primary brain tumors are the most frequent solid tumors in the pediatric age. Among them the medulloblastoma is the prevalent malignant tumor in childhood while pilocytic astrocytoma is the most common, rarely showing a malignant progression. Due to the limited availability of this kind of sample, the study was applied to pooled tumor tissues for a preliminary investigation. The results showed different proteomic profiles of the two tumors and evidenced interesting differential expression of several proteins and peptides. Top-down proteomics of acid-soluble fractions of brain tumor homogenates ascribed a potential biomarker role of malignancy to β- and α-thymosins and their truncated proteoforms and to C-terminal truncated (des-GG) ubiquitin, resulting exclusively detected or over-expressed in the highly malignant medulloblastoma. The bottom-up proteomics of the acid-soluble fraction identified several proteins, some of them in common with 2-DE analysis of acid-insoluble pellets. Peroxiredoxin-1, peptidyl-prolyl cis-trans isomerase A, triosephosphate isomerase, pyruvate kinase PKM, tubulin beta and alpha chains, heat shock protein HSP-90-beta and different histones characterized the medulloblastoma while the Ig kappa chain C region, serotransferrin, tubulin beta 2A chain and vimentin the pilocytic astrocytoma. The two proteomic strategies, with their pros and cons, well complemented each other in characterizing the proteome of brain tumor tissues and in disclosing potential disease biomarkers to be validated in a future study on individual samples of both tumor histotypes. PMID:25909245

  18. Dysembryoplastic neuroepithelial tumor: A rare brain tumor not to be misdiagnosed

    PubMed Central

    Sukheeja, Deepti; Mehta, Jayanti

    2016-01-01

    Dysembryoplastic neuroepithelial tumor (DNET) is a recently described, morphologically unique, and surgically curable low-grade brain tumor which is included in the latest WHO classification as neuronal and mixed neuronal-glial tumor. It is usually seen in children and young adults. The importance of this particular entity is that it is a surgically curable neuroepithelial neoplasm. When recognized, the need for adjuvant radiotherapy and chemotherapy is obviated. We hereby present a case report of an 8-year-old male child who presented with intractable seizures and parieto-occipital space occupying lesion. Histologically, the tumor exhibited features of WHO grade I dysembryoplastic neuroepithelial tumor which was further confirmed by immunohistochemistry. PMID:27057233

  19. Dysembryoplastic neuroepithelial tumor: A rare brain tumor not to be misdiagnosed.

    PubMed

    Sukheeja, Deepti; Mehta, Jayanti

    2016-01-01

    Dysembryoplastic neuroepithelial tumor (DNET) is a recently described, morphologically unique, and surgically curable low-grade brain tumor which is included in the latest WHO classification as neuronal and mixed neuronal-glial tumor. It is usually seen in children and young adults. The importance of this particular entity is that it is a surgically curable neuroepithelial neoplasm. When recognized, the need for adjuvant radiotherapy and chemotherapy is obviated. We hereby present a case report of an 8-year-old male child who presented with intractable seizures and parieto-occipital space occupying lesion. Histologically, the tumor exhibited features of WHO grade I dysembryoplastic neuroepithelial tumor which was further confirmed by immunohistochemistry. PMID:27057233

  20. MRI of brain tissue oxygen tension under hyperbaric conditions.

    PubMed

    Muir, Eric R; Cardenas, Damon P; Duong, Timothy Q

    2016-06-01

    The brain depends on a continuous supply of oxygen to maintain its structural and functional integrity. This study measured T1 from MRI under normobaric air, normobaric oxygen, hyperbaric air, and hyperbaric oxygen (HBO) conditions as a marker of tissue pO2 since dissolved molecular oxygen acts as an endogenous contrast agent. Brain tissue T1 decreased corresponding to increased pO2 with increasing inhaled oxygen concentrations, and tissue oxygenation was estimated from the T1 changes between different inhaled oxygen levels. Tissue pO2 difference maps between different oxygen conditions showed heterogeneous pO2 changes in the brain. MRI-derived tissue pO2 was markedly lower than the arterial pO2 but was slightly higher than venous pO2. Additionally, for comparison with published extracellular tissue pO2 data obtained using oxygen electrodes and other invasive techniques, a model was used to estimate extracellular and intracellular pO2 from the MRI-derived mean tissue pO2. This required multiple assumptions, and so the effects of the assumptions and parameters used in modeling brain pO2 were evaluated. MRI-derived pO2 values were strongly dependent on assumptions about the extra- and intracellular compartments but were relatively less sensitive to variations in the relaxivity constant of oxygen and contribution from oxygen in the cerebral blood compartment. This approach may prove useful in evaluating tissue oxygenation in disease states such as stroke. PMID:27033683

  1. Efficient multilevel brain tumor segmentation with integrated bayesian model classification.

    PubMed

    Corso, J J; Sharon, E; Dube, S; El-Saden, S; Sinha, U; Yuille, A

    2008-05-01

    We present a new method for automatic segmentation of heterogeneous image data that takes a step toward bridging the gap between bottom-up affinity-based segmentation methods and top-down generative model based approaches. The main contribution of the paper is a Bayesian formulation for incorporating soft model assignments into the calculation of affinities, which are conventionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema in multichannel magnetic resonance (MR) volumes. The computationally efficient method runs orders of magnitude faster than current state-of-the-art techniques giving comparable or improved results. Our quantitative results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of glioblastoma multiforme brain tumor. PMID:18450536

  2. Mechanical response of brain tissue under blast loading.

    PubMed

    Laksari, Kaveh; Sadeghipour, Keyanoush; Darvish, Kurosh

    2014-04-01

    In this study, a framework for understanding the propagation of stress waves in brain tissue under blast loading has been developed. It was shown that tissue nonlinearity and rate dependence are the key parameters in predicting the mechanical behavior under such loadings, as they determine whether traveling waves could become steeper and eventually evolve into shock discontinuities. To investigate this phenomenon, in the present study, brain tissue has been characterized as a quasi-linear viscoelastic (QLV) material and a nonlinear constitutive model has been developed for the tissue that spans from medium loading rates up to blast rates. It was shown that development of shock waves is possible inside the head in response to high rate compressive pressure waves. Finally, it was argued that injury to the nervous tissue at the microstructural level could be partly attributed to the high stress gradients with high rates generated at the shock front and this was proposed as a mechanism of injury in brain tissue. PMID:24457112

  3. The time course of steroid action on blood-to-brain and blood-to-tumor transport of 82Rb: A positron emission tomographic study

    SciTech Connect

    Jarden, J.O.; Dhawan, V.; Moeller, J.R.; Strother, S.C.; Rottenberg, D.A.

    1989-03-01

    Blood-to-brain and blood-to-tumor transport rate constants for Rb (K1) and apparent tissue blood volume (Vb) were estimated in 8 patients with primary or metastatic brain tumors before and approximately 6 hours after a 100-mg intravenous bolus injection of dexamethasone using /sup 82/Rb and positron emission tomography. Eight additional patients were studied to evaluate test-retest variability and repositioning errors. Six hours following dexamethasone administration tumor K1 (but not Vb) was significantly reduced compared with contralateral control brain regions (p less than 0.03). These data are consistent with our previously published 24-hour-postdexamethasone data and suggest that comparable effects of corticosteroids on brain/tumor capillaries may be observed at 5 to 6 and 24 hours. The time course of dexamethasone-induced alterations in brain/tumor capillary permeability supports the view that these alterations may be responsible for at least some of the antiedema effects of corticosteroids.

  4. Brain tumor-targeted delivery and therapy by focused ultrasound introduced doxorubicin-loaded cationic liposomes.

    PubMed

    Lin, Qian; Mao, Kai-Li; Tian, Fu-Rong; Yang, Jing-Jing; Chen, Pian-Pian; Xu, Jie; Fan, Zi-Liang; Zhao, Ya-Ping; Li, Wen-Feng; Zheng, Lei; Zhao, Ying-Zheng; Lu, Cui-Tao

    2016-02-01

    Brain tumor lacks effective delivery system for treatment. Focused ultrasound (FUS) can reversibly open BBB without impacts on normal tissues. As a potential drug carrier, cationic liposomes (CLs) have the ability to passively accumulate in tumor tissues for their positive charge. In this study, FUS introduced doxorubicin-loaded cationic liposomes (DOX-CLs) were applied to improve the efficiency of glioma-targeted delivery. Doxorubicin-loaded CLs (DOX-CLs) and quantum dot-loaded cationic liposomes (QD-CLs) were prepared using extrusion technology, and their characterizations were evaluated. With the advantage of QDs in tracing images, the glioma-targeted accumulation of FUS + CLs was evaluated by fluorescence imaging and flow cytometer. Cell survival rate, tumor volume, animal survival time, and brain histology in C6 glioma model were investigated to evaluate the glioma-targeted delivery of FUS + DOX-CLs. DOX-CLs and QD-CLs had suitable nanoscale sizes and high entrapment efficiency. The combined strategy of FUS introduced CLs significantly increased the glioma-targeted accumulation for load drugs. FUS + DOX-CLs showed the strongest inhibition on glioma based on glioma cell in vitro and glioma model in vivo experiments. From MRI and histological analysis, FUS + DOX-CLs group strongly suppressed the glioma progression and extended the animal survival time to 81.2 days. Among all the DOX treatment groups, FUS + DOX-CLs group showed the best cell viability and highest level of tumor apoptosis and necrosis. Combining the advantages of BBB reversible opening by FUS and glioma-targeted binding by CLs, ultrasound introduced cationic liposomes could achieve glioma-targeted delivery, which might be developed as a potential strategy for future brain tumor therapy. PMID:26666650

  5. Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine

    SciTech Connect

    Wienhard, K.; Herholz, K.; Coenen, H.H.; Rudolf, J.; Kling, P.; Stoecklin, G.H.; Heiss, W.D. )

    1991-07-01

    The uptake of L-(2-18F)fluorotyrosine (F-Tyr), a newly synthetized amino acid tracer, was studied in 15 patients with various brain tumors by dynamic PET. The higher F-Tyr accumulation in tumors (mean 27% above contralateral tissue) was associated with two-fold transport rates into tumors, while the rate constants describing irreversible incorporation were decreased. The increased F-Tyr transport was not correlated to 68Ga-EDTA accumulation and cannot be explained by disruption of the blood-brain barrier. Kinetic analysis of 2-(18F)-fluoro-deoxy-glucose accumulation in the same patients demonstrated that increased metabolic rates in tumors are mainly caused by altered phosphorylation rates while transport of glucose is less affected. Since F-Tyr transport rates clearly separated tumors from normal tissue and since F-Tyr accumulation was related to tumor grade, PET studies of F-Tyr uptake are of clinical value for diagnosis and classification of brain tumors.

  6. [The activity of redox-regulatory systems in the tumor and its surrounding tissues in various histological types of tumor].

    PubMed

    Surikova, E I; Goroshinskaja, I A; Nerodo, G A; Frantsiyants, E M; Malejko, M L; Shalashnaja, E V; Kachesova, P; Nemashkalova, L A; Leonova, A V

    2016-01-01

    According to modern concepts cancer is a complex dynamic system having multiple relationships with both the immediate environment and with remote nonmalignant tissues and organs. Changes in the redox balance in them can result in disruption of the normal tissue control. Understanding of the biology of redox processes in a particular tumor and its surroundings, and of their functioning mechanisms is necessary for the development of new anti-cancer strategies based on the effects on the redox state of the tumor and surrounding tissue. Thus the aim of this work was to investigate activity of enzymatic systems influencing the redox state in the tumor tissue, peritumoral area and nonmalignant tissue (taken along the line of resection) for different histological types of tumors. The data obtained showed a similar level of reduced glutathione (GSH) in tumor tissues of gastric adenocarcinoma and vulvar squamous cell carcinoma, but its dynamics in the tissues surrounding the tumor was different. In contrast to the gastric adenocarcinoma the carcinoma of the vulva had a significant level of GSH and higher activity of glutathione dependent enzymes in the tumor tissue and its peritumoral area compared with the surrounding nonmalignant tissue. The results indicate that there are differences in the functioning of the redox regulatory systems in the tumor tissue and its surrounding tissues of various histological origin and localization, possibly due to different mechanisms involved in maintenance of the redox balance in the originally nonmalignant tissue. PMID:27143378

  7. Sigma and opioid receptors in human brain tumors

    SciTech Connect

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. )

    1990-01-01

    Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using ({sup 3}H) 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: {mu}, (D-ala{sup 2}, mePhe{sup 4}, gly-ol{sup 5}) enkephalin (DAMGE); {kappa}, ethylketocyclazocine (EKC) or U69,593; {delta}, (D-pen{sup 2}, D-pen{sup 5}) enkephalin (DPDPE) or (D-ala{sup 2}, D-leu{sup 5}) enkephalin (DADLE) with {mu} suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. {kappa} opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

  8. Heavy Metals and Epigenetic Alterations in Brain Tumors

    PubMed Central

    Caffo, Maria; Caruso, Gerardo; Fata, Giuseppe La; Barresi, Valeria; Visalli, Maria; Venza, Mario; Venza, Isabella

    2014-01-01

    Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature. PMID:25646073

  9. Heavy metals and epigenetic alterations in brain tumors.

    PubMed

    Caffo, Maria; Caruso, Gerardo; Fata, Giuseppe La; Barresi, Valeria; Visalli, Maria; Venza, Mario; Venza, Isabella

    2014-12-01

    Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature. PMID:25646073

  10. Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging

    NASA Astrophysics Data System (ADS)

    Singh-Moon, Rajinder P.; Roblyer, Darren M.; Bigio, Irving J.; Joshi, Shailendra

    2014-09-01

    We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a cross-correlation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.

  11. Brain tumor imaging using small-angle x-ray scattering tomography

    NASA Astrophysics Data System (ADS)

    Jensen, Torben H.; Bech, Martin; Bunk, Oliver; Thomsen, Maria; Menzel, Andreas; Bouchet, Audrey; Le Duc, Géraldine; Feidenhans'l, Robert; Pfeiffer, Franz

    2011-03-01

    We demonstrate high-resolution small-angle x-ray scattering computed tomography (SAXS-CT) of soft matter and soft tissue samples. Complete SAXS patterns over extended ranges of momentum transfer are reconstructed spatially resolved from volumes inside an extended sample. Several SAXS standard samples are used to quantitatively validate the method and demonstrate its performance. Further results on biomedical tissue samples (rat brains) are presented that demonstrate the advantages of the method compared to existing biomedical x-ray imaging approaches. Functional areas of the brains as well as tumor morphology are imaged. By providing insights into the structural organization at the nano-level, SAXS-CT complements and extends results obtainable with standard methods such as x-ray absorption tomography and histology.

  12. Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

    PubMed Central

    Sarin, Hemant

    2009-01-01

    Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof. PMID:19723323

  13. Joint segmentation and deformable registration of brain scans guided by a tumor growth model.

    PubMed

    Gooya, Ali; Pohl, Kilian M; Bilello, Michel; Biros, George; Davatzikos, Christos

    2011-01-01

    This paper presents an approach for joint segmentation and deformable registration of brain scans of glioma patients to a normal atlas. The proposed method is based on the Expectation Maximization (EM) algorithm that incorporates a glioma growth model for atlas seeding, a process which modifies the normal atlas into one with a tumor and edema. The modified atlas is registered into the patient space and utilized for the posterior probability estimation of various tissue labels. EM iteratively refines the estimates of the registration parameters, the posterior probabilities of tissue labels and the tumor growth model parameters. We have applied this approach to 10 glioma scans acquired with four Magnetic Resonance (MR) modalities (T1, T1-CE, T2 and FLAIR) and validated the result by comparing them to manual segmentations by clinical experts. The resulting segmentations look promising and quantitatively match well with the expert provided ground truth. PMID:21995070

  14. Waves of ratcheting cancer cells in growing tumor tissue layer

    NASA Astrophysics Data System (ADS)

    Yang, Taeseok; Kwon, Tae; Kim, Hyun; Lee, Kyoung; CenterCell Dynamics Team

    2015-03-01

    Over many years researchers have shown that the mechanical forces generated by, and acting on, tissues influence the way they grow, develop and migrate. As for cancer research goes, understanding the role of these forces may even be as influential as deciphering the relevant genetic and molecular basis. Often the key issues in the field of cancer mechanics are to understand the interplay of mechanics and chemistry. In this study, we discuss very intriguing population density waves observed in slowly proliferating of tumor cell layers. The temporal periods are around 4 hr and their wavelength is in the order of 1 mm. Tumor cell layer, which is initially plated in a small disk area, expands as a band of tumor cells is ``ratcheting'' in concert in radially outward direction. By adding Cytochalasin D and Latrunculin B, an inhibitor of actin polymerization, or Mytomycin, a chemotherapeutic agent, we could halt and modulate the wave activities reversibly. The observed waves are visually quite similar to those of chemotaxing dictyostelium discodium amoeba population, which are driven by nonlinear chemical reaction-diffusion waves of cAMP. So far, we have not been able to show any relevant chemo-attractants inducing the collective behavior of these tumor cells. Researchers have been investigating how forces from both within and outside developing cancer cells interact in intricate feedback loops. This work reports the example of periodic density waves of tumor cells with an explanation purely based on nonlinear mechanics.

  15. Radiosensitization by nicotinamide in tumors and normal tissues: the importance of tissue oxygenation status

    SciTech Connect

    Horsman, M.R.; Hansen, P.V.; Overgaard, J.

    1989-05-01

    Nicotinamide induced radiosensitization of tumors has been suggested to be a consequence of a reduction in tumor hypoxia. We have investigated the possibility that nicotinamide may produce significant radiosensitization in a normal tissue in which the radiation response is also influenced by hypoxia. The normal tissue studied was testis and radiation damage was assessed by measuring survival of spermatogonial stem cells. The radiosensitizing action of nicotinamide in testis was compared to that observed in a C3H mammary carcinoma when assayed by both regrowth delay and local tumor control. Our results show that nicotinamide (1000 mg/kg; i.p.) enhanced radiation damage in both tissue types when the radiation was given up to at least 3 hr after drug injection. Enhancement ratios obtained when the drug and radiation were separated by a 1 hr time interval were between 1.1 to 1.2 for the testis and 1.0 to 1.5 for the tumor. The results suggest that nicotinamide will produce radiosensitization in testis, but the effect is small and less than that observed in tumors.

  16. Divergent viral presentation among human tumors and adjacent normal tissues.

    PubMed

    Cao, Song; Wendl, Michael C; Wyczalkowski, Matthew A; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J; Gay, Hiram; Chen, Ken; Rader, Janet S; Dipersio, John F; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  17. Divergent viral presentation among human tumors and adjacent normal tissues

    PubMed Central

    Cao, Song; Wendl, Michael C.; Wyczalkowski, Matthew A.; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J.; Gay, Hiram; Chen, Ken; Rader, Janet S.; Dipersio, John F.; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  18. Retro-inverso bradykinin opens the door of blood-brain tumor barrier for nanocarriers in glioma treatment.

    PubMed

    Xie, Zuoxu; Shen, Qing; Xie, Cao; Lu, Weiyue; Peng, Chunmei; Wei, Xiaoli; Li, Xue; Su, Bingxia; Gao, Chunli; Liu, Min

    2015-12-01

    The blood-brain barrier and the blood-brain tumor barrier (BBTB) prevent most drugs entering brain tumors. Complicated preparation procedures of drug delivery systems and damage to normal brain tissue have limited the application of many strategies for the treatment of brain tumor in clinical trials. We have designed a bradykinin analog, retro-inverso bradykinin (RI-BK), which is characterized by resistance to proteolysis and high binding activity with the bradykinin type 2 (B2) receptor. After systemic administration, RI-BK binds to B2 receptors and induces a change in zonula occluden-1 and depolymerization of F-actin to selectively open the BBTB. RI-BK increased the accumulation of drug-loaded nanocarriers in the glioma but not in normal brain. Co-administration with RI-BK enhanced the therapeutic efficiency of drug-loaded nanocarriers for glioma. These findings suggest that RI-BK could be translated into the clinic as an adjunctive treatment for malignant brain tumors. PMID:26282786

  19. Comparing implementations of magnetic-resonance-guided fluorescence molecular tomography for diagnostic classification of brain tumors

    NASA Astrophysics Data System (ADS)

    Davis, Scott C.; Samkoe, Kimberley S.; O'Hara, Julia A.; Gibbs-Strauss, Summer L.; Paulsen, Keith D.; Pogue, Brian W.

    2010-09-01

    Fluorescence molecular tomography (FMT) systems coupled to conventional imaging modalities such as magnetic resonance imaging (MRI) and computed tomography provide unique opportunities to combine data sets and improve image quality and content. Yet, the ideal approach to combine these complementary data is still not obvious. This preclinical study compares several methods for incorporating MRI spatial prior information into FMT imaging algorithms in the context of in vivo tissue diagnosis. Populations of mice inoculated with brain tumors that expressed either high or low levels of epidermal growth factor receptor (EGFR) were imaged using an EGF-bound near-infrared dye and a spectrometer-based MRI-FMT scanner. All data were spectrally unmixed to extract the dye fluorescence from the tissue autofluorescence. Methods to combine the two data sets were compared using student's t-tests and receiver operating characteristic analysis. Bulk fluorescence measurements that made up the optical imaging data set were also considered in the comparison. While most techniques were able to distinguish EGFR(+) tumors from EGFR(-) tumors and control animals, with area-under-the-curve values=1, only a handful were able to distinguish EGFR(-) tumors from controls. Bulk fluorescence spectroscopy techniques performed as well as most imaging techniques, suggesting that complex imaging algorithms may be unnecessary to diagnose EGFR status in these tissue volumes.

  20. [A brain tissue bank in a neuropathology laboratory. Basic methodology].

    PubMed

    Rivas, E; Teijeira, S; Tardio, A; Fachal, C; Quintáns, B; Navarro, C

    2003-12-01

    The Meixoeiro Hospital Brain Bank (BB) was established at the end of 2002. A BB is a tissue collection and storage system, established under the best conditions to carry out prospective morphological, biochemical or molecular studies. The BB should ideally be supported by a donor program, although samples may also be obtained from autopsy material from patients with neurodegenerative diseases. Recruitment of control cases from brains without neurological diseases is basic. The main goal of a BB is to provide brain tissue for research. Each case requires accurate clinical data, a definite diagnosis and optimal conditions of tissue preservation. The use of protocols to standardize the handling and processing of tissues, data recruitment and neuropathological diagnosis is fundamental to assure the quality and homogeneity of samples. Close collaboration between neuropathologists, neurologists and other specialists is essential in all the process. Although important advances in the tissue banking field have been achieved, the number of donors in Spain still remains low. Stronger institutional support as well as public awareness through better diffusion of the information is necessary to increase the number of donors and improve BB development. PMID:14648346

  1. Brain tumor segmentation in MRI by using the fuzzy connectedness method

    NASA Astrophysics Data System (ADS)

    Liu, Jian-Guo; Udupa, Jayaram K.; Hackney, David; Moonis, Gul

    2001-07-01

    The aim of this paper is the precise and accurate quantification of brain tumor via MRI. This is very useful in evaluating disease progression, response to therapy, and the need for changes in treatment plans. We use multiple MRI protocols including FLAIR, T1, and T1 with Gd enhancement to gather information about different aspects of the tumor and its vicinity- edema, active regions, and scar left over due to surgical intervention. We have adapted the fuzzy connectedness framework to segment tumor and to measure its volume. The method requires only limited user interaction in routine clinical MRI. The first step in the process is to apply an intensity normalization method to the images so that the same body region has the same tissue meaning independent of the scanner and patient. Subsequently, a fuzzy connectedness algorithm is utilized to segment the different aspects of the tumor. The system has been tested, for its precision, accuracy, and efficiency, utilizing 40 patient studies. The percent coefficient of variation (% CV) in volume due to operator subjectivity in specifying seeds for fuzzy connectedness segmentation is less than 1%. The mean operator and computer time taken per study is 3 minutes. The package is designed to run under operator supervision. Delineation has been found to agree with the operators' visual inspection most of the time except in some cases when the tumor is close to the boundary of the brain. In the latter case, the scalp is included in the delineation and an operator has to exclude this manually. The methodology is rapid, robust, consistent, yielding highly reproducible measurements, and is likely to become part of the routine evaluation of brain tumor patients in our health system.

  2. Optical properties of tumor tissues grown on the chorioallantoic membrane of chicken eggs: tumor model to assay of tumor response to photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Honda, Norihiro; Kariyama, Yoichiro; Hazama, Hisanao; Ishii, Takuya; Kitajima, Yuya; Inoue, Katsushi; Ishizuka, Masahiro; Tanaka, Tohru; Awazu, Kunio

    2015-12-01

    Herein, the optical adequacy of a tumor model prepared with tumor cells grown on the chorioallantoic membrane (CAM) of a chicken egg is evaluated as an alternative to the mouse tumor model to assess the optimal irradiation conditions in photodynamic therapy (PDT). The optical properties of CAM and mouse tumor tissues were measured with a double integrating sphere and the inverse Monte Carlo technique in the 350- to 1000-nm wavelength range. The hemoglobin and water absorption bands observed in the CAM tumor tissue (10 eggs and 10 tumors) are equal to that of the mouse tumor tissue (8 animals and 8 tumors). The optical intersubject variability of the CAM tumor tissues meets or exceeds that of the mouse tumor tissues, and the reduced scattering coefficient spectra of CAM tumor tissues can be equated with those of mouse tumor tissues. These results confirm that the CAM tumor model is a viable alternative to the mouse tumor model, especially for deriving optimal irradiation conditions in PDT.

  3. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    SciTech Connect

    Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.; Vitaz, Todd W.; Spalding, Aaron C.

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  4. A Novel Semi-Supervised Methodology for Extracting Tumor Type-Specific MRS Sources in Human Brain Data

    PubMed Central

    Ortega-Martorell, Sandra; Ruiz, Héctor; Vellido, Alfredo; Olier, Iván; Romero, Enrique; Julià-Sapé, Margarida; Martín, José D.; Jarman, Ian H.; Arús, Carles; Lisboa, Paulo J. G.

    2013-01-01

    Background The clinical investigation of human brain tumors often starts with a non-invasive imaging study, providing information about the tumor extent and location, but little insight into the biochemistry of the analyzed tissue. Magnetic Resonance Spectroscopy can complement imaging by supplying a metabolic fingerprint of the tissue. This study analyzes single-voxel magnetic resonance spectra, which represent signal information in the frequency domain. Given that a single voxel may contain a heterogeneous mix of tissues, signal source identification is a relevant challenge for the problem of tumor type classification from the spectroscopic signal. Methodology/Principal Findings Non-negative matrix factorization techniques have recently shown their potential for the identification of meaningful sources from brain tissue spectroscopy data. In this study, we use a convex variant of these methods that is capable of handling negatively-valued data and generating sources that can be interpreted as tumor class prototypes. A novel approach to convex non-negative matrix factorization is proposed, in which prior knowledge about class information is utilized in model optimization. Class-specific information is integrated into this semi-supervised process by setting the metric of a latent variable space where the matrix factorization is carried out. The reported experimental study comprises 196 cases from different tumor types drawn from two international, multi-center databases. The results indicate that the proposed approach outperforms a purely unsupervised process by achieving near perfect correlation of the extracted sources with the mean spectra of the tumor types. It also improves tissue type classification. Conclusions/Significance We show that source extraction by unsupervised matrix factorization benefits from the integration of the available class information, so operating in a semi-supervised learning manner, for discriminative source identification and brain

  5. General solutions to poroviscoelastic model of hydrocephalic human brain tissue.

    PubMed

    Mehrabian, Amin; Abousleiman, Younane

    2011-12-21

    Hydrocephalus is a well-known disorder of brain fluidic system. It is commonly associated with complexities in cerebrospinal fluid (CSF) circulation in brain. In this paper, hydrocephalus and shunting surgery which is used in its treatment are modeled. Brain tissues are considered to follow a poroviscoelastic constitutive model in order to address the effects of time dependence of mechanical properties of soft tissues and fluid flow hydraulics. Our solution draws from Biot's theory of poroelasticity, generalized to account for viscoelastic effects through the correspondence principle. Geometrically, the brain is conceived to be spherically symmetric, where the ventricles are assumed to be a hollow concentric space filled with cerebrospinal fluid. A generalized Kelvin model is considered for the rheological properties of brain tissues. The solution presented is useful in the analysis of the disorder of hydrocephalus as well as the treatment associated with it, namely, ventriclostomy surgery. The sensitivity of the solution to various factors such as aqueduct blockage level and trabeculae stiffness is thoroughly analyzed using numerical examples. Results indicate that partial aqueduct stenosis may be a cause of hydrocephalus. However, only severe occlusion of the aqueduct can cause a significant increase in the ventricle and brain's extracellular fluid pressure. Ventriculostomy shunts are commonly used as a remedy to hydrocephalus. They serve to reduce the ventricular pressure to the normal level. However, sensitivity analysis on the shunt's fluid deliverability parameter has shown that inappropriate design or selection of design shunt may cause under-drainage or over-drainage of the ventricles. Excessive drainage of CSF may increase the normal tensile stress on trabeculae. It can cause rupture of superior cerebral veins or damage to trabeculae or even brain tissues which in turn may lead to subdural hematoma, a common side-effect of the surgery. These Post

  6. Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

    ClinicalTrials.gov

    2016-08-15

    Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors

  7. Neonatal Brain Tissue Classification with Morphological Adaptation and Unified Segmentation

    PubMed Central

    Beare, Richard J.; Chen, Jian; Kelly, Claire E.; Alexopoulos, Dimitrios; Smyser, Christopher D.; Rogers, Cynthia E.; Loh, Wai Y.; Matthews, Lillian G.; Cheong, Jeanie L. Y.; Spittle, Alicia J.; Anderson, Peter J.; Doyle, Lex W.; Inder, Terrie E.; Seal, Marc L.; Thompson, Deanne K.

    2016-01-01

    Measuring the distribution of brain tissue types (tissue classification) in neonates is necessary for studying typical and atypical brain development, such as that associated with preterm birth, and may provide biomarkers for neurodevelopmental outcomes. Compared with magnetic resonance images of adults, neonatal images present specific challenges that require the development of specialized, population-specific methods. This paper introduces MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation), which extends the unified segmentation approach to tissue classification implemented in Statistical Parametric Mapping (SPM) software to neonates. MANTiS utilizes a combination of unified segmentation, template adaptation via morphological segmentation tools and topological filtering, to segment the neonatal brain into eight tissue classes: cortical gray matter, white matter, deep nuclear gray matter, cerebellum, brainstem, cerebrospinal fluid (CSF), hippocampus and amygdala. We evaluated the performance of MANTiS using two independent datasets. The first dataset, provided by the NeoBrainS12 challenge, consisted of coronal T2-weighted images of preterm infants (born ≤30 weeks' gestation) acquired at 30 weeks' corrected gestational age (n = 5), coronal T2-weighted images of preterm infants acquired at 40 weeks' corrected gestational age (n = 5) and axial T2-weighted images of preterm infants acquired at 40 weeks' corrected gestational age (n = 5). The second dataset, provided by the Washington University NeuroDevelopmental Research (WUNDeR) group, consisted of T2-weighted images of preterm infants (born <30 weeks' gestation) acquired shortly after birth (n = 12), preterm infants acquired at term-equivalent age (n = 12), and healthy term-born infants (born ≥38 weeks' gestation) acquired within the first 9 days of life (n = 12). For the NeoBrainS12 dataset, mean Dice scores comparing MANTiS with manual segmentations were all above 0.7, except for the cortical gray

  8. The brain tissue response to surgical injury and its possible contribution to glioma recurrence.

    PubMed

    Hamard, Lauriane; Ratel, David; Selek, Laurent; Berger, François; van der Sanden, Boudewijn; Wion, Didier

    2016-05-01

    Surgery is the first line therapy for glioma. However, glioma recurs in 90 % of the patients in the resection margin. The impact of surgical brain injury (SBI) on glioma recurrence is largely overlooked. Herein, we review some of the mechanisms involved in tissue repair that may impact glioma recurrence at the resection margin. Many processes or molecules involved in tissue repair after brain injury are also critical for glioma growth. They include a wide array of secreted growth factors, cytokines and transcription factors including NFКB and STAT3 which in turn activate proliferative and anti-apoptotic genes and processes such as angiogenesis and inflammation. Because some residual glioma cells always remain in the tumor resection margin, there are now compelling arguments to suggest that some aspects of the brain tissue response to SBI can also participate to glioma recurrence at the resection margin. Brain tissue response to SBI recruits angiogenesis and inflammation that precede and then follow tumor recurrence at the resection margin. The healing response to SBI is double edged, as inflammation is involved in regeneration and healing, and has both pro- and anti-tumorigenic functions. A promising therapeutic approach is to normalize and re-educate the molecular and cellular responses at the resection margin to promote anti-tumorigenic processes involved in healing while inhibiting pro-tumorigenic activities. Manipulation of the inflammatory response to SBI to prevent local recurrence could also enhance the efficacy of other therapies such as immunotherapy. However, our current knowledge is far from sufficient to achieve this goal. Acknowledging, understanding and manipulating the double-edged role played by SBI in glioma recurrence is surely challenging, but it cannot be longer delayed. PMID:26961772

  9. Transistor needle chip for recording in brain tissue

    NASA Astrophysics Data System (ADS)

    Felderer, Florian; Fromherz, Peter

    2011-07-01

    We report on a proof-of-principle experiment for the direct interfacing of transistors with intact brain tissue. A transistor needle chip (TNC) with a TiO2 surface is fabricated from a silicon-on-insulator wafer and impaled into an acute brain slice cut from hippocampus of the rat. While stimulating the Schaffer collateral, a local field potential is recorded in stratum radiatum of the CA1 region with field-effect transistors in the central part of the slice where the tissue is not damaged by the cutting process. After the impalement, the signal amplitude is small. Within an hour, it increases to a stable level around -2 mV as is recorded with a conventional micropipette electrode. The recovery indicates that the tissue is able to adapt to the impaled chip. Upon repeated impalements at the same position, the large signal is observed without delay. A profile of the transistor signal across the slice is due to the boundary conditions of a brain slice with both surfaces held near ground potential. The experiments with the TNC prototype are a basis for the development of silicon needle chips with a large multi-transistor array (MTA) for applications in brain-computer interfacing.

  10. Functional Tissue Pulsatility Imaging of the Brain during Visual Stimulation

    PubMed Central

    Kucewicz, John C.; Dunmire, Barbrina; Leotta, Daniel F.; Panagiotides, Heracles; Paun, Marla; Beach, Kirk W.

    2007-01-01

    Functional tissue pulsatility imaging (fTPI) is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility due to changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, non-ultrasound technology for measuring expansion of a whole limb or body part due to perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow and relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile “plethysmographic” signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate Analysis of Variance (MANOVA) was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 out 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex. PMID:17346872

  11. [Soft tissue tumors - the view of the molecular biologist].

    PubMed

    Krsková, Lenka; Mrhalová, Marcela; Kalinová, Markéta; Campr, Vít; Capková, Linda; Grega, Marek; Háček, Jaromír; Hornofová, Ludmila; Chadimová, Mária; Chmelová, Renata; Kodetová, Daniela; Zámečník, Josef; Kodet, Roman

    2014-07-01

    Soft tissue tumors (SSTs) constitute a broad spectrum of neoplasms with diverse biological properties. Rare or unusual types are often difficult to classify. Recent studies show, that a significant subset of SSTs including many types of sarcomas are associated with specific genetic changes such as chromosomal translocations producing chimeric genes, which play a role in the pathogenesis of SSTs. Because SSTs represent a diagnostically challenging group of tumors, molecular-genetic techniques (FISH or PCR) are useful as supplementary and/or confirmatory diagnostic tools. In the present paper we demonstrate the usefulness of a combined diagnostic approach using the tools of classical histopathology and immunohistochemistry together with the molecular diagnostic approach in selected nosologic entites. PMID:25186594

  12. Studies on porphyrin photoproducts in solution, cells, and tumor tissue

    NASA Astrophysics Data System (ADS)

    Koenig, Karsten; Schneckenburger, Herbert; Rueck, Angelika C.; Koenig, Roland

    1994-07-01

    Light excitation of photosensitizing porphyrins leads to cytotoxic reactions. In addition, photobleaching and photoproduct formation occur indicating photosensitizer destruction. Photoproducts from hematoporphyrin (HP) fluoresce in aqueous solution at 642 nm, whereas photoproducts from protoporphyrin (PP) in hydrophobic environment emit around 670 nm and exhibit pronounced absorption at 665 nm. Photoproduct formation depends on singlet oxygen. The photoproducts exhibit faster fluorescence decay kinetics compared with nonirradiated porphyrins, as shown by time-grated spectroscopy and fluorescence decay measurements. Photoproduct fluorescence was observed during light exposure of cells and of tumor-bearing, nude mice, following administration of Hematoporphyrin Derivative (HpD), tetramethyl-HP, and PP. Photoconversion was also detected with naturally-occurring porphyrins (PP-producing bacteria) and ALA-simulated biosynthesis of PP in tumor tissue and in skin lesions of patients (psoriasis, mycosis fungoides). The efficiency of PDT with porphyrin photoproducts was found to be low in spite of the strong electronic transitions in the red spectral region.

  13. An automatic method of brain tumor segmentation from MRI volume based on the symmetry of brain and level set method

    NASA Astrophysics Data System (ADS)

    Li, Xiaobing; Qiu, Tianshuang; Lebonvallet, Stephane; Ruan, Su

    2010-02-01

    This paper presents a brain tumor segmentation method which automatically segments tumors from human brain MRI image volume. The presented model is based on the symmetry of human brain and level set method. Firstly, the midsagittal plane of an MRI volume is searched, the slices with potential tumor of the volume are checked out according to their symmetries, and an initial boundary of the tumor in the slice, in which the tumor is in the largest size, is determined meanwhile by watershed and morphological algorithms; Secondly, the level set method is applied to the initial boundary to drive the curve evolving and stopping to the appropriate tumor boundary; Lastly, the tumor boundary is projected one by one to its adjacent slices as initial boundaries through the volume for the whole tumor. The experiment results are compared with hand tracking of the expert and show relatively good accordance between both.

  14. The role of IDO in brain tumor immunotherapy

    PubMed Central

    Zhai, Lijie; Lauing, Kristen L.; Chang, Alan L.; Dey, Mahua; Qian, Jun; Cheng, Yu; Lesniak, Maciej S.; Wainwright, Derek A.

    2015-01-01

    Malignant glioma comprises the majority of primary brain tumors. Coincidently, most of those malignancies express an inducible tryptophan catabolic enzyme, indoleamine 2,3 dioxygenase 1 (IDO1). While IDO1 is not normally expressed at appreciable levels in the adult central nervous system, it's rapidly induced and/or upregulated upon inflammatory stimulus. The primary function of IDO1 is associated with conversion of the essential amino acid, tryptophan, into downstream catabolites known as kynure-nines. The depletion of tryptophan and/or accumulation of kynurenine has been shown to induce T cell deactivation, apoptosis and/or the induction of immunosuppressive programming via the expression of FoxP3. This understanding has informed immunotherapeutic design for the strategic development of targeted molecular therapeutics that inhibit IDO1 activity. Here, we review the current knowledge of IDO1 in brain tumors, pre-clinical studies targeting this enzymatic pathway, alternative tryptophan catabolic mediators that compensate for IDO1 loss and/or inhibition, as well as proposed clinical strategies and questions that are critical to address for increasing future immunotherapeutic effectiveness in patients with incurable brain cancer. PMID:25519303

  15. Round Randomized Learning Vector Quantization for Brain Tumor Imaging

    PubMed Central

    2016-01-01

    Brain magnetic resonance imaging (MRI) classification into normal and abnormal is a critical and challenging task. Owing to that, several medical imaging classification techniques have been devised in which Learning Vector Quantization (LVQ) is amongst the potential. The main goal of this paper is to enhance the performance of LVQ technique in order to gain higher accuracy detection for brain tumor in MRIs. The classical way of selecting the winner code vector in LVQ is to measure the distance between the input vector and the codebook vectors using Euclidean distance function. In order to improve the winner selection technique, round off function is employed along with the Euclidean distance function. Moreover, in competitive learning classifiers, the fitting model is highly dependent on the class distribution. Therefore this paper proposed a multiresampling technique for which better class distribution can be achieved. This multiresampling is executed by using random selection via preclassification. The test data sample used are the brain tumor magnetic resonance images collected from Universiti Kebangsaan Malaysia Medical Center and UCI benchmark data sets. Comparative studies showed that the proposed methods with promising results are LVQ1, Multipass LVQ, Hierarchical LVQ, Multilayer Perceptron, and Radial Basis Function. PMID:27516807

  16. Round Randomized Learning Vector Quantization for Brain Tumor Imaging.

    PubMed

    Sheikh Abdullah, Siti Norul Huda; Bohani, Farah Aqilah; Nayef, Baher H; Sahran, Shahnorbanun; Al Akash, Omar; Iqbal Hussain, Rizuana; Ismail, Fuad

    2016-01-01

    Brain magnetic resonance imaging (MRI) classification into normal and abnormal is a critical and challenging task. Owing to that, several medical imaging classification techniques have been devised in which Learning Vector Quantization (LVQ) is amongst the potential. The main goal of this paper is to enhance the performance of LVQ technique in order to gain higher accuracy detection for brain tumor in MRIs. The classical way of selecting the winner code vector in LVQ is to measure the distance between the input vector and the codebook vectors using Euclidean distance function. In order to improve the winner selection technique, round off function is employed along with the Euclidean distance function. Moreover, in competitive learning classifiers, the fitting model is highly dependent on the class distribution. Therefore this paper proposed a multiresampling technique for which better class distribution can be achieved. This multiresampling is executed by using random selection via preclassification. The test data sample used are the brain tumor magnetic resonance images collected from Universiti Kebangsaan Malaysia Medical Center and UCI benchmark data sets. Comparative studies showed that the proposed methods with promising results are LVQ1, Multipass LVQ, Hierarchical LVQ, Multilayer Perceptron, and Radial Basis Function. PMID:27516807

  17. Boron Neutron Capture Therapy for Malignant Brain Tumors

    PubMed Central

    MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  18. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

    Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

    2016-07-15

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  19. Mitochondrial Control by DRP1 in Brain Tumor Initiating Cells

    PubMed Central

    Xie, Qi; Wu, Qiulian; Horbinski, Craig M.; Flavahan, William A.; Yang, Kailin; Zhou, Wenchao; Dombrowski, Stephen M.; Huang, Zhi; Fang, Xiaoguang; Shi, Yu; Ferguson, Ashley N.; Kashatus, David F.; Bao, Shideng; Rich, Jeremy N.

    2015-01-01

    Brain tumor initiating cells (BTICs) coopt the neuronal high affinity GLUT3 glucose transporter to withstand metabolic stress. Here, we investigated another mechanism critical to brain metabolism, mitochondrial morphology. BTICs displayed mitochondrial fragmentation relative to non-BTICs, suggesting that BTICs have increased mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), was activated in BTICs and inhibited in non-BTICs. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and AMPK targeting rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca2+–calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTICs, suggesting tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlates with poor prognosis in glioblastoma, suggesting mitochondrial dynamics may represent a therapeutic target for BTICs. PMID:25730670

  20. Exploratory case-control study of brain tumors in adults

    SciTech Connect

    Burch, J.D.; Craib, K.J.; Choi, B.C.; Miller, A.B.; Risch, H.A.; Howe, G.R.

    1987-04-01

    An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.

  1. Intranasal delivery of mesenchymal stem cells significantly extends survival of irradiated mice with experimental brain tumors.

    PubMed

    Balyasnikova, Irina V; Prasol, Melanie S; Ferguson, Sherise D; Han, Yu; Ahmed, Atique U; Gutova, Margarita; Tobias, Alex L; Mustafi, Devkumar; Rincón, Esther; Zhang, Lingjiao; Aboody, Karen S; Lesniak, Maciej S

    2014-01-01

    Treatment options of glioblastoma multiforme are limited due to the blood-brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell-based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. ¹¹¹In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of (¹¹¹In)-oxine-labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell-based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma. PMID:24002694

  2. Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors

    PubMed Central

    Balyasnikova, Irina V; Prasol, Melanie S; Ferguson, Sherise D; Han, Yu; Ahmed, Atique U; Gutova, Margarita; Tobias, Alex L; Mustafi, Devkumar; Rincón, Esther; Zhang, Lingjiao; Aboody, Karen S; Lesniak, Maciej S

    2014-01-01

    Treatment options of glioblastoma multiforme are limited due to the blood–brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell–based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. 111In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of 111In-oxine–labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell–based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma. PMID:24002694

  3. Dosimetric Comparison Between 3DCRT and IMRT Using Different Multileaf Collimators in the Treatment of Brain Tumors

    SciTech Connect

    Ding Meisong Newman, Francis M.S.; Chen Changhu; Stuhr, Kelly; Gaspar, Laurie E.

    2009-04-01

    We investigated the differences between 3-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT), and the impact of collimator leaf-width on IMRT plans for the treatment of nonspherical brain tumors. Eight patients treated by 3DCRT with Novalis were selected. We developed 3 IMRT plans with different multileaf collimators (Novalis m3, Varian MLC-120, and Varian MLC-80) with the same treatment margins, number of beams, and gantry positions as in the 3DCRT treatment plans. Treatment planning utilized the BrainLAB treatment planning system. For each patient, the dose constraints and optimization parameters remained identical for all plans. The heterogeneity index, the percentage target coverage, critical structures, and normal tissue volumes receiving 50% of the prescription dose were calculated to compare the dosimetric difference. Equivalent uniform dose (EUD) and tumor control probability (TCP) were also introduced to evaluate the radiobiological effect for different plans. We found that IMRT significantly improved the target dose homogeneity compared to the 3DCRT. However, IMRT showed the same radiobiological effect as 3DCRT. For the brain tumors adjacent to (or partially overlapping with) critical structures, IMRT dramatically spared the volume of the critical structures to be irradiated. In IMRT plans, the smaller collimator leaf width could reduce the volume of critical structures irradiated to the 50% level for those partially overlapping with the brain tumors. For relatively large and spherical brain tumors, the smaller collimator leaf widths give no significant benefit.

  4. Pc 4 photodynamic therapy of U87 (human glioma) orthotopic tumor in nude rat brain

    NASA Astrophysics Data System (ADS)

    Dean, David; George, John E., III; Ahmad, Yusra; Wolfe, Michael S.; Lilge, Lothar; Morris, Rachel L.; Peterson, Allyn; Lust, W. D.; Totonchi, Ali; Varghai, Davood; Li, Xiaolin; Hoppel, Charles L.; Sun, Jiayang; Oleinick, Nancy L.

    2005-04-01

    Introduction: Photodynamic therapy (PDT) for Barrett"s esophagus, advanced esophageal cancer, and both early and late inoperable lung carcinoma is now FDA-approved using the first generation photosensitizer PhotofrinTM (Axcan Pharma, Birmingham, AL). Photofrin-mediated PDT of glioma is now in Phase III clinical trials. A variety of second generation photosensitizers have been developed to provide improved: (1) specificity for the target tissue, (2) tumoricidal capability, and (3) rapid clearance the vascular compartment, skin, and eyes. The phthalocyanine Pc 4 is a second generation photosensitizer that is in early phase I clinical trials for skin cancer. We have undertaken a preclinical study that seeks to determine if Pc 4-mediated PDT can be of benefit for the intra-operative localization and treatment of glioma. Methods: Using a stereotactic frame, 250,000 U87 cells were injected via Hamilton syringe through a craniotomy, and the dura, 1-2 mm below the cortical surface of nude (athymic) rat brains (N=91). The craniotomy was filled with a piece of surgical PVC and the scalp closed. After two weeks of tumor growth, the animals received 0.5 mg/kg Pc 4 via tail vein injection. One day later the scalp was re-incised, and the PVC removed. The tumor was then illuminated with either 5 or 30 Joule/cm2 of 672-nm light from a diode laser at 50 mW/cm2. The animals were sacrificed one day later and the brain was cold-perfused with formaldehyde. Two thirds of the explanted brains are now being histologically surveyed for necrosis after staining with hematoxylin and eosin and for apoptosis via immunohistochemistry (i.e., TUNEL assay). The other third were analyzed by HPLC-mass spectrometry for the presence of drug in tumor, normal brain, and plasma at sacrifice. Initial histological results show PDT-induced apoptosis and necrosis confined to the growing (live) portion of the tumor. Preliminary analysis shows an average selectivity of Pc 4 uptake in the bulk tumor to be 3

  5. Tumors of the brain and nervous system after radiotherapy in childhood

    SciTech Connect

    Ron, E.; Modan, B.; Boice, J.D. Jr.; Alfandary, E.; Stovall, M.; Chetrit, A.; Katz, L.

    1988-10-20

    We investigated the relation between radiotherapy in childhood for tinea capitis and the later development of tumors of the brain and nervous system among 10,834 patients treated between 1948 and 1960 in Israel. Benign and malignant tumors were identified from the pathology records of all Israeli hospitals and from Israeli national cancer and death registries. Doses of radiation to the neural tissue were retrospectively estimated for each patient (mean, 1.5 Gy). Sixty neural tumors developed in the patients exposed as children, and the 30-year cumulative risk (+/- SE) was 0.8 +/- 0.2 percent. The incidence of tumors was 1.8 per 10,000 persons per year. The estimated relative risk as compared with that for 10,834 matched general-population controls and 5392 siblings who had not been irradiated was 6.9 (95 percent confidence interval, 4.1 to 11.6) for all tumors and 8.4 (confidence interval, 4.8 to 14.8) when the analysis was restricted to neural tumors of the head and neck. Increased risks were apparent for meningiomas (relative risk, 9.5; n = 19), gliomas (relative risk, 2.6; n = 7), nerve-sheath tumors (relative risk, 18.8; n = 25), and other neural tumors (relative risk, 3.4; n = 9). A strong dose--response relation was found, with the relative risk approaching 20 after estimated doses of approximately 2.5 Gy. Our study confirms that radiation doses on the order of 1 to 2 Gy can significantly increase the risk of neural tumors.

  6. Application of the total reflection X-ray fluorescence method to the elemental analysis of brain tumors of different types and grades of malignancy

    NASA Astrophysics Data System (ADS)

    Lankosz, M. W.; Grzelak, M.; Ostachowicz, B.; Wandzilak, A.; Szczerbowska-Boruchowska, M.; Wrobel, P.; Radwanska, E.; Adamek, D.

    2014-11-01

    The process of carcinogenesis may influence normal biochemical reactions leading to alterations in the elemental composition of the tissue. Total reflection X-ray fluorescence analysis (TXRF) was applied to the elemental analysis of different brain tumors. The following elements were present in all the neoplastic tissues analyzed: K, Ca, Fe, Cu, Zn and Rb. The results of the analysis showed that the elemental composition of a relatively small fragment of tissue represents satisfactorily the biochemical “signature” of a cancer. On the basis of the element concentrations determined, it was possible to differentiate between some types of brain tumors.

  7. Comparison of visual metric and planimetry methods for brain tumor measurement in dogs.

    PubMed

    Thomson, Chris B; Haynes, Kevin H; Pluhar, G Elizabeth

    2016-05-01

    OBJECTIVE To compare the orthogonal diameter (visual metric) method against a manual perimeter tracing (planimetry) method to measure volume of brain tumors in dogs by use of MRI scans. SAMPLE 22 sets of MRI brain scans pertaining to 22 client-owned dogs with histologically confirmed glioma. PROCEDURES MRI scans were reviewed by 2 operators, and scans revealing tumors with a degree of gadolinium enhancement that allowed discrimination between tumor tissue and healthy parenchyma were used. Each operator calculated tumor volume for each set of scans twice by use of visual metric and planimetry methods. Inter- and intraoperator variability were assessed by calculation of an agreement index (AI). RESULTS Mean ± SD intraoperator AIs were 0.79 ± 0.24 for the visual metric method and 0.89 ± 0.17 for the planimetry method. Intraoperator variability for both operators was significantly less when the planimetry method was used than when the visual metric method was used. No significant differences were identified in mean interoperator AI between visual metric (0.68 ± 0.28) and planimetry (0.67 ± 0.31) methods. CONCLUSIONS AND CLINICAL RELEVANCE The lower intraoperator variability achieved with the planimetry versus visual metric method should result in more precise volume assessments when the same operator performs multiple volume measurements of brain tumors in dogs. Equivocal results for interoperator variability may have been due to method variance or inadequate preliminary training. Additional studies are needed to evaluate the suitability of planimetry for assessing response to treatment. PMID:27111014

  8. Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue. [Mice

    SciTech Connect

    Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

    1983-04-01

    Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy.

  9. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

    PubMed Central

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2013-01-01

    The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain disease (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951–61) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539–52). PMID:24033426

  10. Automatic Segmentation of Eight Tissue Classes in Neonatal Brain MRI

    PubMed Central

    Anbeek, Petronella; Išgum, Ivana; van Kooij, Britt J. M.; Mol, Christian P.; Kersbergen, Karina J.; Groenendaal, Floris; Viergever, Max A.; de Vries, Linda S.; Benders, Manon J. N. L.

    2013-01-01

    Purpose Volumetric measurements of neonatal brain tissues may be used as a biomarker for later neurodevelopmental outcome. We propose an automatic method for probabilistic brain segmentation in neonatal MRIs. Materials and Methods In an IRB-approved study axial T1- and T2-weighted MR images were acquired at term-equivalent age for a preterm cohort of 108 neonates. A method for automatic probabilistic segmentation of the images into eight cerebral tissue classes was developed: cortical and central grey matter, unmyelinated and myelinated white matter, cerebrospinal fluid in the ventricles and in the extra cerebral space, brainstem and cerebellum. Segmentation is based on supervised pixel classification using intensity values and spatial positions of the image voxels. The method was trained and evaluated using leave-one-out experiments on seven images, for which an expert had set a reference standard manually. Subsequently, the method was applied to the remaining 101 scans, and the resulting segmentations were evaluated visually by three experts. Finally, volumes of the eight segmented tissue classes were determined for each patient. Results The Dice similarity coefficients of the segmented tissue classes, except myelinated white matter, ranged from 0.75 to 0.92. Myelinated white matter was difficult to segment and the achieved Dice coefficient was 0.47. Visual analysis of the results demonstrated accurate segmentations of the eight tissue classes. The probabilistic segmentation method produced volumes that compared favorably with the reference standard. Conclusion The proposed method provides accurate segmentation of neonatal brain MR images into all given tissue classes, except myelinated white matter. This is the one of the first methods that distinguishes cerebrospinal fluid in the ventricles from cerebrospinal fluid in the extracerebral space. This method might be helpful in predicting neurodevelopmental outcome and useful for evaluating neuroprotective clinical

  11. [Study of distribution of 169Yb, 69Ga and 111In in tumor tissues by macroautoradiography; comparison between viable and necrotic tumor tissues].

    PubMed

    Ando, A; Doishita, K; Sanada, S; Ando, I; Hiraki, T

    1977-01-01

    The localization of 169Yb, 67Ga and 111In in tumor tissues was determined macroautoradiographically. 169Yb-citrate and 111In-citrate were injected intravenously to the rats subcutaneously transplanted Yoshida sarcoma and were injected intraperitoneally to the mice subcutaneously transplanted Ehrlich tumor. These animals were sacrificed 3, 24 and 48 hours after injection. These tumor tissues were frozen in n-hexane (-70 degrees C) cooled with dry ice-acetone. After this, these frozen tumor tissues were cut into serial thin sections (10 micron) in the cryostat (-20 degrees C). One of the slice of these sections was then placed on X-ray film and this film was developed after exposure of several days. On the other hand, next slice of these sections were then stained using the hematoxylin and eosin. From the observations of these autoradiogram and H-E stained slice, the following results were obtained. Concentration of 169Yb, 67Ga and 111In was predominant in viable tumor tissue rather than in necrotic tumor tissue, regardless of time after the administration. 67Ga and 111In were distributed uniformly in viable tumor tissue, but deposition of 169Yb was observed more avidly in viabl tumor tissue neighboring to necrotic tumor. PMID:577017

  12. Statistical feature selection for enhanced detection of brain tumor

    NASA Astrophysics Data System (ADS)

    Chaddad, Ahmad; Colen, Rivka R.

    2014-09-01

    Feature-based methods are widely used in the brain tumor recognition system. Robust of early cancer detection is one of the most powerful image processing tools. Specifically, statistical features, such as geometric mean, harmonic mean, mean excluding outliers, median, percentiles, skewness and kurtosis, have been extracted from brain tumor glioma to aid in discriminating two levels namely, Level I and Level II using fluid attenuated inversion recovery (FLAIR) sequence in the diagnosis of brain tumor. Statistical feature describes the major characteristics of each level from glioma which is an important step to evaluate heterogeneity of cancer area pixels. In this paper, we address the task of feature selection to identify the relevant subset of features in the statistical domain, while discarding those that are either redundant or confusing, thereby improving the performance of feature-based scheme to distinguish between Level I and Level II. We apply a Decision Structure algorithm to find the optimal combination of nonhomogeneity based statistical features for the problem at hand. We employ a Naïve Bayes classifier to evaluate the performance of the optimal statistical feature based scheme in terms of its glioma Level I and Level II discrimination capability and use real-data collected from 17 patients have a glioblastoma multiforme (GBM). Dataset provided from 3 Tesla MR imaging system by MD Anderson Cancer Center. For the specific data analyzed, it is shown that the identified dominant features yield higher classification accuracy, with lower number of false alarms and missed detections, compared to the full statistical based feature set. This work has been proposed and analyzed specific GBM types which Level I and Level II and the dominant features were considered as feature aid to prognostic indicators. These features were selected automatically to be better able to determine prognosis from classical imaging studies.

  13. Identifying the needs of brain tumor patients and their caregivers.

    PubMed

    Parvataneni, Rupa; Polley, Mei-Yin; Freeman, Teresa; Lamborn, Kathleen; Prados, Michael; Butowski, Nicholas; Liu, Raymond; Clarke, Jennifer; Page, Margaretta; Rabbitt, Jane; Fedoroff, Anne; Clow, Emelia; Hsieh, Emily; Kivett, Valerie; Deboer, Rebecca; Chang, Susan

    2011-09-01

    The purpose of this study is to identify the needs of brain tumor patients and their caregivers to provide improved health services to these populations. Two different questionnaires were designed for patients and caregivers. Both questionnaires contained questions pertaining to three realms: disease symptoms/treatment, health care provider, daily living/finances. The caregivers' questionnaires contained an additional domain on emotional needs. Each question was evaluated for the degree of importance and satisfaction. Exploratory analyses determined whether baseline characteristics affect responder importance or satisfaction. Also, areas of high agreement/disagreement in satisfaction between the participating patient-caregiver pairs were identified. Questions for which >50% of the patients and caregivers thought were "very important" but >30% were dissatisfied include: understanding the cause of brain tumors, dealing with patients' lower energy, identifying healthful foods and activities for patients, telephone access to health care providers, information on medical insurance coverage, and support from their employer. In the emotional realm, caregivers identified 9 out of 10 items as important but need further improvement. Areas of high disagreement in satisfaction between participating patient-caregiver pairs include: getting help with household chores (P value = 0.006) and finding time for personal needs (P value < 0.001). This study provides insights into areas to improve services for brain tumor patients and their caregivers. The caregivers' highest amount of burden is placed on their emotional needs, emphasizing the importance of providing appropriate medical and psychosocial support for caregivers to cope with emotional difficulties they face during the patients' treatment process. PMID:21311950

  14. Chemoselective imaging of mouse brain tissue via multiplex CARS microscopy.

    PubMed

    Pohling, Christoph; Buckup, Tiago; Pagenstecher, Axel; Motzkus, Marcus

    2011-08-01

    The fast and reliable characterization of pathological tissue is a debated topic in the application of vibrational spectroscopy in medicine. In the present work we apply multiplex coherent anti-Stokes Raman scattering (MCARS) to the investigation of fresh mouse brain tissue. The combination of imaginary part extraction followed by principal component analysis led to color contrast between grey and white matter as well as layers of granule and Purkinje cells. Additional quantitative information was obtained by using a decomposition algorithm. The results perfectly agree with HE stained references slides prepared separately making multiplex CARS an ideal approach for chemoselective imaging. PMID:21833351

  15. Tumor Directed, Scalp Sparing Intensity Modulated Whole Brain Radiotherapy for Brain Metastases.

    PubMed

    Kao, Johnny; Darakchiev, Boramir; Conboy, Linda; Ogurek, Sara; Sharma, Neha; Ren, Xuemin; Pettit, Jeffrey

    2015-10-01

    Despite significant technical advances in radiation delivery, conventional whole brain radiation therapy (WBRT) has not materially changed in the past 50 years. We hypothesized that IMRT can selectively spare uninvolved brain and scalp with the goal of reducing acute and late toxicity. MRI/CT simulation image registration was performed. We performed IMRT planning to simultaneously treat the brain tumor(s) on MRI + 5 mm margin to 37.5 Gy in 15 fractions while limiting the uninvolved brain + 2 mm margin to 30 Gy in 15 fractions and the mean scalp dose to #18 Gy. Three field IMRT plans were compared to conventional WBRT plans. Symptomatic patients were started on conventional WBRT for 2 to 3 fractions while IMRT planning was performed. Seventeen consecutive patients with brain metastases with RPA class I and II disease with no leptomeningeal spread were treated with IMRT WBRT. Compared to conventional WBRT, IMRT reduced the mean scalp dose (26.2 Gy vs. 16.4 Gy, p < 0.001) and the mean PTV30 dose (38.4 Gy vs. 32.0 Gy, p < 0.001) while achieving similar mean PTV37.5 doses (38.3 Gy vs. 38.0 Gy, p = 0.26). Using Olsen hair loss score criteria, 4 of 15 assessable patients preserved at least 50% of hair coverage at 1 to 3 months after treatment while 6 patients preserved between 25 and 50% hair coverage. At a median follow-up of 6.8 months (range: 5 to 15 months), the median overall survival was 5.4 months. Four patients relapsed within the brain, one within the PTV37.5 and three outside the PTV37.5. Tumor directed, scalp sparing IMRT is feasible, achieves rational dose distributions and preserves partial hair coverage in the majority of patients. Further studies are warranted to determine whether the increased utilization of resources needed for IMRT are appropriate in this setting. PMID:24750002

  16. Three-Staged Stereotactic Radiotherapy Without Whole Brain Irradiation for Large Metastatic Brain Tumors

    SciTech Connect

    Higuchi, Yoshinori Serizawa, Toru; Nagano, Osamu; Matsuda, Shinji; Ono, Junichi; Sato, Makoto; Iwadate, Yasuo; Saeki, Naokatsu

    2009-08-01

    Purpose: To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm{sup 3} in volume. Patients and Methods: Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (> 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 {+-} 6.3 cm{sup 3} (mean {+-} SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method. Results: At the time of the second and third fractions, mean tumor volumes were 14.3 {+-} 6.5 (18.8% reduction) and 10.6 {+-} 6.1 cm{sup 3} (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively. Conclusions: The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases.

  17. Confidence-based ensemble for GBM brain tumor segmentation

    NASA Astrophysics Data System (ADS)

    Huo, Jing; van Rikxoort, Eva M.; Okada, Kazunori; Kim, Hyun J.; Pope, Whitney; Goldin, Jonathan; Brown, Matthew

    2011-03-01

    It is a challenging task to automatically segment glioblastoma multiforme (GBM) brain tumors on T1w post-contrast isotropic MR images. A semi-automated system using fuzzy connectedness has recently been developed for computing the tumor volume that reduces the cost of manual annotation. In this study, we propose a an ensemble method that combines multiple segmentation results into a final ensemble one. The method is evaluated on a dataset of 20 cases from a multi-center pharmaceutical drug trial and compared to the fuzzy connectedness method. Three individual methods were used in the framework: fuzzy connectedness, GrowCut, and voxel classification. The combination method is a confidence map averaging (CMA) method. The CMA method shows an improved ROC curve compared to the fuzzy connectedness method (p < 0.001). The CMA ensemble result is more robust compared to the three individual methods.

  18. Collective Behavior of Brain Tumor Cells: the Role of Hypoxia

    NASA Astrophysics Data System (ADS)

    Khain, Evgeniy; Katakowski, Mark; Hopkins, Scott; Szalad, Alexandra; Zheng, Xuguang; Jiang, Feng; Chopp, Michael

    2013-03-01

    We consider emergent collective behavior of a multicellular biological system. Specifically we investigate the role of hypoxia (lack of oxygen) in migration of brain tumor cells. We performed two series of cell migration experiments. The first set of experiments was performed in a typical wound healing geometry: cells were placed on a substrate, and a scratch was done. In the second set of experiments, cell migration away from a tumor spheroid was investigated. Experiments show a controversy: cells under normal and hypoxic conditions have migrated the same distance in the ``spheroid'' experiment, while in the ``scratch'' experiment cells under normal conditions migrated much faster than under hypoxic conditions. To explain this paradox, we formulate a discrete stochastic model for cell dynamics. The theoretical model explains our experimental observations and suggests that hypoxia decreases both the motility of cells and the strength of cell-cell adhesion. The theoretical predictions were further verified in independent experiments.

  19. Histone H3 Mutations in Pediatric Brain Tumors

    PubMed Central

    Liu, Xiaoyang; McEachron, Troy A.; Schwartzentruber, Jeremy; Wu, Gang

    2014-01-01

    Until recently, mutations in histones had not been described in any human disease. However, genome-wide sequencing of pediatric high-grade gliomas revealed somatic heterozygous mutations in the genes encoding histones H3.1 and H3.3, as well as mutations in the chromatin modifiers ATRX and DAXX. The functional significance and mechanistic details of how these mutations affect the tumors is currently under intensive investigation. The information gained from these studies will shed new light on normal brain development as well as increase our understanding of the tumorigenic processes that drive pediatric high-grade gliomas. PMID:24691963

  20. The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS).

    PubMed

    Menze, Bjoern H; Jakab, Andras; Bauer, Stefan; Kalpathy-Cramer, Jayashree; Farahani, Keyvan; Kirby, Justin; Burren, Yuliya; Porz, Nicole; Slotboom, Johannes; Wiest, Roland; Lanczi, Levente; Gerstner, Elizabeth; Weber, Marc-André; Arbel, Tal; Avants, Brian B; Ayache, Nicholas; Buendia, Patricia; Collins, D Louis; Cordier, Nicolas; Corso, Jason J; Criminisi, Antonio; Das, Tilak; Delingette, Hervé; Demiralp, Çağatay; Durst, Christopher R; Dojat, Michel; Doyle, Senan; Festa, Joana; Forbes, Florence; Geremia, Ezequiel; Glocker, Ben; Golland, Polina; Guo, Xiaotao; Hamamci, Andac; Iftekharuddin, Khan M; Jena, Raj; John, Nigel M; Konukoglu, Ender; Lashkari, Danial; Mariz, José Antonió; Meier, Raphael; Pereira, Sérgio; Precup, Doina; Price, Stephen J; Raviv, Tammy Riklin; Reza, Syed M S; Ryan, Michael; Sarikaya, Duygu; Schwartz, Lawrence; Shin, Hoo-Chang; Shotton, Jamie; Silva, Carlos A; Sousa, Nuno; Subbanna, Nagesh K; Szekely, Gabor; Taylor, Thomas J; Thomas, Owen M; Tustison, Nicholas J; Unal, Gozde; Vasseur, Flor; Wintermark, Max; Ye, Dong Hye; Zhao, Liang; Zhao, Binsheng; Zikic, Darko; Prastawa, Marcel; Reyes, Mauricio; Van Leemput, Koen

    2015-10-01

    In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource. PMID:25494501

  1. Absence of human cytomegalovirus infection in childhood brain tumors.

    PubMed

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors. PMID:26396923

  2. Absence of human cytomegalovirus infection in childhood brain tumors

    PubMed Central

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients’ neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors. PMID:26396923

  3. [Exchange reactions in brain tissue under chronic ethanol intoxication].

    PubMed

    Gil'miiarova, F N; Radomskaia, V M; Vinogradova, L N

    1982-01-01

    The paper deals with characterization of systems utilizing ethanol and reactions conjugated with its exchange in the brain tissue under chronic alcohol intoxication. The following is established: the absence of the alcoholdehydrogenase pathway of ethanol oxidation in rabbits, unbalanced splitting of carbohydrates under two-months ethanol load, disturbance of oxidative processes in the tricarboxylic acids cycle, a decrease in the pool of oxidized nicotin amide coenzymes. PMID:7036487

  4. Pharmacological mitigation of tissue damage during brain microdialysis.

    PubMed

    Nesbitt, Kathryn M; Jaquins-Gerstl, Andrea; Skoda, Erin M; Wipf, Peter; Michael, Adrian C

    2013-09-01

    Microdialysis sampling in the brain is employed frequently in the chemical analysis of neurological function and disease, but implanting the probes, which are substantially larger than the size and spacing of brain cells and blood vessels, is injurious and triggers ischemia, gliosis, and cell death at the sampling site. The nature of the interface between the brain and the microdialysis probe is critical to the use of microdialysis as a neurochemical analysis technique. The objective of the work reported here was to investigate the potential of two compounds, dexamethasone, a glucocorticoid anti-inflammatory agent, and XJB-5-131, a mitochondrially targeted reactive oxygen species scavenger, to mitigate the penetration injury. Measurements were performed in the rat brain striatum, which is densely innervated by axons that release dopamine, an electroactive neurotransmitter. We used voltammetry to measure electrically evoked dopamine release next to microdialysis probes during the retrodialysis of dexamethasone or XJB-5-131. After the in vivo measurements, the brain tissue containing the microdialysis probe tracks was examined by fluorescence microscopy using markers for ischemia, neuronal nuclei, macrophages, and dopamine axons and terminals. Dexamethasone and XJB-5-131 each diminished the loss of evoked dopamine activity, diminished ischemia, diminished the loss of neuronal nuclei, diminished the appearance of extravasated macrophages, and diminished the loss of dopamine axons and terminals next to the probes. Our findings confirm the ability of dexamethasone and XJB-5-131 to mitigate, but not eliminate, the effects of the penetration injury caused by implanting microdialysis probes into brain tissue. PMID:23927692

  5. Potassium Channel Complex Autoimmunity Induced by Inhaled Brain Tissue Aerosol

    PubMed Central

    Meeusen, Jeffrey W.; Klein, Christopher J.; Pirko, Istvan; Haselkorn, Keegan E.; Kryzer, Thomas J.; Pittock, Sean J.; Lachance, Daniel H.; Dyck, P. James; Lennon, Vanda A.

    2011-01-01

    Objective Test the hypothesis that autoimmunity induced by inhalation of aerosolized brain tissue caused outbreaks of sensory-predominant polyradiculoneuropathy among swine abattoir employees in Midwestern USA Methods Mice were exposed intranasally, 5 days weekly, to liquefied brain tissue. Serum from exposed mice, patients and unaffected abattoir employees were analyzed for clinically pertinent neural autoantibodies. Results Patients, coworkers and mice exposed to liquefied brain tissue had an autoantibody profile dominated by neural cation channel IgGs. The most compelling link between patients and exposed mice was MRI evidence of grossly swollen spinal nerve roots. Autoantibody responses in patients and mice were dose-dependent and declined after antigen exposure ceased. Autoantibodies detected most frequently, and at high levels, bound to detergent-solubilized macromolecular complexes containing neuronal voltage-gated potassium channels ligated with a high affinity Kv1 channel antagonist, 125I-α-dendrotoxin. Exposed mice exhibited a behavioral phenotype consistent with potassium channel dysfunction recognized in drosophila with mutant (“shaker”) channels: reduced sensitivity to isoflurane-induced anesthesia. Pathological and electrophysiological findings in patients supported peripheral nerve hyperexcitability over destructive axonal loss. The pain-predominant symptoms were consistent with sensory nerve hyperexcitability Interpretation Our observations establish that inhaled neural antigens readily induce neurological autoimmunity and identify voltage-gated potassium channel complexes as a major immunogen. PMID:22451206

  6. In vivo bubble nucleation probability in sheep brain tissue.

    PubMed

    Gateau, J; Aubry, J-F; Chauvet, D; Boch, A-L; Fink, M; Tanter, M

    2011-11-21

    Gas nuclei exist naturally in living bodies. Their activation initiates cavitation activity, and is possible using short ultrasonic excitations of high amplitude. However, little is known about the nuclei population in vivo, and therefore about the rarefaction pressure required to form bubbles in tissue. A novel method dedicated to in vivo investigations was used here that combines passive and active cavitation detection with a multi-element linear ultrasound probe (4-7 MHz). Experiments were performed in vivo on the brain of trepanated sheep. Bubble nucleation was induced using a focused single-element transducer (central frequency 660 kHz, f-number = 1) driven by a high power (up to 5 kW) electric burst of two cycles. Successive passive recording and ultrafast active imaging were shown to allow detection of a single nucleation event in brain tissue in vivo. Experiments carried out on eight sheep allowed statistical studies of the bubble nucleation process. The nucleation probability was evaluated as a function of the peak negative pressure. No nucleation event could be detected with a peak negative pressure weaker than -12.7 MPa, i.e. one order of magnitude higher than the recommendations based on the mechanical index. Below this threshold, bubble nucleation in vivo in brain tissues is a random phenomenon. PMID:22015981

  7. Tumor growth model for atlas based registration of pathological brain MR images

    NASA Astrophysics Data System (ADS)

    Moualhi, Wafa; Ezzeddine, Zagrouba

    2015-02-01

    The motivation of this work is to register a tumor brain magnetic resonance (MR) image with a normal brain atlas. A normal brain atlas is deformed in order to take account of the presence of a large space occupying tumor. The method use a priori model of tumor growth assuming that the tumor grows in a radial way from a starting point. First, an affine transformation is used in order to bring the patient image and the brain atlas in a global correspondence. Second, the seeding of a synthetic tumor into the brain atlas provides a template for the lesion. Finally, the seeded atlas is deformed combining a method derived from optical flow principles and a model for tumor growth (MTG). Results show that an automatic segmentation method of brain structures in the presence of large deformation can be provided.

  8. The modern brain tumor operating room: from standard essentials to current state-of-the-art.

    PubMed

    Barnett, Gene H; Nathoo, Narendra

    2004-01-01

    It is just over a century since successful brain tumor resection. Since then the diagnosis, imaging, and management of brain tumors have improved, in large part due to technological advances. Similarly, the operating room (OR) for brain tumor surgery has increased in complexity and specificity with multiple forms of equipment now considered necessary as technical adjuncts. It is evident that the theme of minimalism in combination with advanced image-guidance techniques and a cohort of sophisticated technologies (e.g., robotics and nanotechnology) will drive changes in the current OR environment for the foreseeable future. In this report we describe what may be regarded today as standard essentials in an operating room for the surgical management of brain tumors and what we believe to be the current 'state-of-the-art' brain tumor OR. Also, we speculate on the additional capabilities of the brain tumor OR of the near future. PMID:15527078

  9. Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors

    PubMed Central

    Stavrinou, Pantelis; Mavrogiorgou, Maria-Christina; Polyzoidis, Konstantinos; Kreft-Kerekes, Vincenzo; Timmer, Marco; Marselos, Marios; Pappas, Periklis

    2015-01-01

    Background Endogenous and exogenous compounds as well as carcinogens are metabolized and detoxified by phase I and II enzymes, the activity of which could be crucial to the inactivation and hence susceptibility to carcinogenic factors. The expression of these enzymes in human brain tumor tissue has not been investigated sufficiently. We studied the association between tumor pathology and the expression profile of seven phase I and II drug metabolizing genes (CYP1A1, CYP1B1, ALDH3A1, AOX1, GSTP1, GSTT1 and GSTM3) and some of their proteins. Methods Using qRT-PCR and western blotting analysis the gene and protein expression in a cohort of 77 tumors were investigated. The major tumor subtypes were meningioma, astrocytoma and brain metastases, -the later all adenocarcinomas from a lung primary. Results Meningeal tumors showed higher expression levels for AOX1, CYP1B1, GSTM3 and GSTP1. For AOX1, GSTM and GSTP1 this could be verified on a protein level as well. A negative correlation between the WHO degree of malignancy and the strength of expression was identified on both transcriptional and translational level for AOX1, GSTM3 and GSTP1, although the results could have been biased by the prevalence of meningiomas and glioblastomas in the inevitably bipolar distribution of the WHO grades. A correlation between the gene expression and the protein product was observed for AOX1, GSTP1 and GSTM3 in astrocytomas. Conclusions The various CNS tumors show different patterns of drug metabolizing gene expression. Our results suggest that the most important factor governing the expression of these enzymes is the histological subtype and to a far lesser extent the degree of malignancy itself. PMID:26580399

  10. [Untoward side effects of chemoradiotherapy in children with malignant brain tumors].

    PubMed

    Morozova, S K; Begun, I V; Spivak, L V; Radiuk, K A; Papkevich, I I; Savich, T V; Pershaĭ, E B; Vashkevich, T I; Aleĭnikova, O V

    2002-01-01

    Untoward side-effects of chemoradiotherapy were compared in 48 children treated for brain tumors and those in remission lasting from less than 12 months to 11 years. The investigation concerned disturbances in the neurologic, endocrine, cardiovascular, urinary, hepatobiliary and psychic systems; neurologic ones proved the most frequent. No cases of heart failure were reported among patients with brain tumors during remission. Hormonal study revealed inhibited thyroid function in brain tumor sufferers. PMID:12455363

  11. The New Kids on the Block: Recently Characterized Soft Tissue Tumors.

    PubMed

    Riddle, Nicole N; Gardner, Jerad M

    2015-09-01

    Soft tissue pathology is a rapidly changing subspecialty. New entities are described relatively often, and new molecular findings for soft tissue tumors are reported in the literature almost every month. This article summarizes the major features and diagnostic approach to several recently characterized entities: superficial CD34-positive fibroblastic tumor, fibrosarcoma-like lipomatous neoplasm, angiofibroma of soft tissue, low-grade sinonasal sarcoma with neural and myogenic features, malignant gastrointestinal neuroectodermal tumor, hemosiderotic fibrolipomatous tumor, and epithelioid inflammatory myofibroblastic sarcoma. Additionally, the article also provides a summary table of recent molecular findings in soft tissue tumors. PMID:26297066

  12. A benchmark analysis of radiation flux distribution for Boron Neutron Capture Therapy of canine brain tumors

    SciTech Connect

    Moran, J.M.

    1992-02-01

    Calculations of radiation flux and dose distributions for Boron Neutron Capture Therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly-heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This work describes a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador Retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador Retriever head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for the model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous tissue model. Comparison of the results showed that the peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.

  13. What's New in Research and Treatment for Brain Tumors in Children?

    MedlinePlus

    ... brain and spinal cord tumors in children What’s new in research and treatment for brain and spinal ... an investigational method, and studies are continuing. Other new treatment strategies Researchers are also testing some newer ...

  14. Nondestructive quantification of permeability of hyperosmotic agent in normal and tumor tissues

    NASA Astrophysics Data System (ADS)

    Xiong, Honglian; Guo, Zhouyi; Zeng, Changchun; Wang, Like; He, Yonghong; Liu, Songhao

    2008-12-01

    Noninvasive tumor imaging could lead to the early detection and timely treatment of cancer. Previous investigations have suggested that optical coherence tomography (OCT) is an ideal diagnostic tool distinguishing normal tissues from tumor tissues based on structural imaging because of the high resolution. In the study, the capability of OCT for functional imaging of normal and tumor tissues based on time and depth resolved quantification of the permeability of biomolecules through these tissues is investigated. An OCT system at 830 nm central wavelength was used in this study. Diffusion of 20% aqueous solution of glucose was monitored and quantified in normal stomach tissues and tumor tissues using OCT. The orthotopic graft model of gastric cancer in nude mice was used. Permeability coefficients were calculated as a function of time and tissue depth. The permeability coefficient was (9.44+/-0.42) ×10-6 cm/s in normal stomach tissues and (5.32+/-0.17)×10-5 cm/s in tumor tissues. The tumor tissues had a higher permeability coefficient compared to normal tissues. From the experimental results, it is found that the accurate and sensitive assessment of the permeability coefficients of normal and tumor tissues offer an effective OCT image method for clinical diagnosis and detection of tumor tissues.

  15. Updates on the cytogenetics and molecular cytogenetics of benign and intermediate soft tissue tumors

    PubMed Central

    NISHIO, JUN

    2013-01-01

    Soft tissue tumors are classified according to their histological resemblance to normal adult tissues and can be grouped into the following categories based on metastatic potential: benign, intermediate (locally aggressive), intermediate (rarely metastasizing) and malignant. Over the past two decades, considerable progress has been made in our understanding of the genetic background of soft tissue tumors. Traditional laboratory techniques, such as cytogenetic analysis and fluorescence in situ hybridization (FISH), can be used for diagnostic purposes in soft tissue pathology practice. Moreover, cytogenetic and molecular studies are often necessary for prognostics and follow-up of soft tissue sarcoma patients. This review provides updated information on the applicability of laboratory genetic testing in the diagnosis of benign and intermediate soft tissue tumors. These tumors include nodular fasciitis, chondroid lipoma, collagenous fibroma (desmoplastic fibroblastoma), giant cell tumor of tendon sheath (GCTTS)/pigmented villonodular synovitis (PVNS), angiofibroma of soft tissue, myxoinflammatory fibroblastic sarcoma (MIFS) and ossifying fibromyxoid tumor (OFMT). PMID:23255885

  16. Cryptococcal Brainstem Abscess Mimicking Brain Tumors in an Immunocompetent Patient

    PubMed Central

    Hur, Jong Hee; Kim, Jang-Hee; Park, Seoung Woo

    2015-01-01

    Usually fungal infections caused by opportunistic and pathogenic fungi had been an important cause of morbidity and mortality among immunocompromised patients. However clinical data and investigations for immunocompetent pathogenic fungal infections had been rare and neglected into clinical studies. Especially Cryptococcal brainstem abscess cases mimicking brain tumors were also much more rare. So we report this unusual case. This 47-year-old man presented with a history of progressively worsening headache and nausea for 1 month and several days of vomituritions before admission. Neurological and laboratory examinations performed demonstrated no abnormal findings. Previously he was healthy and did not have any significant medical illnesses. A CT and MRI scan revealed enhancing 1.8×1.7×2.0 cm mass lesion in the left pons having central necrosis and peripheral edema compressing the fourth ventricle. And also positron emission tomogram scan demonstrated a hot uptake of fluoro-deoxy-glucose on the brainstem lesion without any evidences of systemic metastasis. Gross total mass resection was achieved with lateral suboccipital approach with neuronavigation system. Postoperatively he recovered without any neurological deficits. Pathologic report confirmed Cryptococcus neoformans and he was successively treated with antifungal medications. This is a previously unreported rare case of brainstem Cryptococcal abscess mimicking brain tumors in immunocompetent host without having any apparent typical meningeal symptoms and signs with resultant good neurosurgical recovery. PMID:25674344

  17. Analgesic use and the risk of primary adult brain tumor.

    PubMed

    Egan, Kathleen M; Nabors, Louis B; Thompson, Zachary J; Rozmeski, Carrie M; Anic, Gabriella A; Olson, Jeffrey J; LaRocca, Renato V; Chowdhary, Sajeel A; Forsyth, Peter A; Thompson, Reid C

    2016-09-01

    Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma. PMID:26894804

  18. Is outpatient brain tumor surgery feasible in India?

    PubMed

    Turel, Mazda K; Bernstein, Mark

    2016-01-01

    The current trend in all fields of surgery is towards less invasive procedures with shorter hospital stays. The reasons for this change include convenience to patients, optimal resource utilization, and cost saving. Technological advances in neurosurgery, aided by improvements in anesthesia, have resulted in surgery that is faster, simpler, and safer with excellent perioperative recovery. As a result of improved outcomes, some centers are performing brain tumor surgery on an outpatient basis, wherein patients arrive at the hospital the morning of their procedure and leave the hospital the same evening, thus avoiding an overnight stay in the hospital. In addition to the medical benefits of the outpatient procedure, its impact on patient satisfaction is substantial. The economic benefits are extremely favorable for the patient, physician, as well as the hospital. In high volume centers, a day surgery program can exist alongside those for elective and emergency surgeries, providing another pathway for patient care. However, due to skepticism surrounding the medicolegal aspects, and how radical the concept at first sounds, these procedures have not gained widespread popularity. We provide an overview of outpatient brain tumor surgery in the western world, discussing the socioeconomic, medicolegal, and ethical issues related to its adaptability in a developing nation. PMID:27625225

  19. Microscopy and chemical imaging of Behcet brain tissue

    NASA Astrophysics Data System (ADS)

    Aranyosiova, Monika; Michalka, Miroslav; Kopani, Martin; Rychly, Boris; Jakubovsky, Jan; Velic, Dusan

    2008-12-01

    Chemical composition and distribution of molecules and elements in a human brain tissue of Behcet diseased patient are of interest. Behcet disease is a multi-system disorder of which pathogenesis and chemical causality are still uncertain. Time-of-flight secondary ion mass spectrometry is used along with scanning electron microscopy and energy dispersive X-ray analysis providing complex composition in Behcet disease and control tissues. Determined organic compounds are represented by fragments of carbohydrates, phospholipids, amino acids, and peptides. The distributions of inorganic species are well represented by heavy trace elements and by oxides in positive and negative polarities of time-of-flight secondary ion mass spectrometry, respectively. Organic and inorganic compounds are qualitatively determined in both samples, Behcet and control, providing complementary chemical images. The complementary chemical images interestingly change with the quantitative regression of organic compounds distribution, characteristic for the healthy control, towards inorganic compounds distribution, characteristic for Behcet tissue.

  20. Fetal brain tumors: Prenatal diagnosis by ultrasound and magnetic resonance imaging

    PubMed Central

    Milani, Hérbene José; Araujo Júnior, Edward; Cavalheiro, Sérgio; Oliveira, Patrícia Soares; Hisaba, Wagner Jou; Barreto, Enoch Quinderé Sá; Barbosa, Maurício Mendes; Nardozza, Luciano Marcondes; Moron, Antonio Fernandes

    2015-01-01

    Congenital central nervous system tumors diagnosed during pregnancy are rare, and often have a poor prognosis. The most frequent type is the teratoma. Use of ultrasound and magnetic resonance image allows the suspicion of brain tumors during pregnancy. However, the definitive diagnosis is only confirmed after birth by histology. The purpose of this mini-review article is to describe the general clinical aspects of intracranial tumors and describe the main fetal brain tumors. PMID:25628801

  1. Fetal brain tumors: Prenatal diagnosis by ultrasound and magnetic resonance imaging.

    PubMed

    Milani, Hérbene José; Araujo Júnior, Edward; Cavalheiro, Sérgio; Oliveira, Patrícia Soares; Hisaba, Wagner Jou; Barreto, Enoch Quinderé Sá; Barbosa, Maurício Mendes; Nardozza, Luciano Marcondes; Moron, Antonio Fernandes

    2015-01-28

    Congenital central nervous system tumors diagnosed during pregnancy are rare, and often have a poor prognosis. The most frequent type is the teratoma. Use of ultrasound and magnetic resonance image allows the suspicion of brain tumors during pregnancy. However, the definitive diagnosis is only confirmed after birth by histology. The purpose of this mini-review article is to describe the general clinical aspects of intracranial tumors and describe the main fetal brain tumors. PMID:25628801

  2. Patterns of MiB-1 staining of brain tumors: microwave-antigen retrieval as a tool in diagnostic pathology.

    PubMed

    Meera, G; Jo, H; Ravi, R

    1995-11-01

    MiB-1 antibody staining can be carried out on formalin fixed, paraffin embedded tissue only if microwave antigen retrieval is performed. This method was used to identify proliferating cells in archival paraffin sections of 137 cases of human brain tumors. The tumors concerned were astrocytomas (57), glioblastomas (16), oligodendrogliomas (11), mixed gliomas (8), ependymomas (9), subependymoma (2), medulloblastomas (4) and meningiomas (30). For the tumors which were histologically graded (the astrocytomas, oligodendrogliomas and ependymomas), generally the scores of MiB-1 staining were correlated with the tumor grade, although there were exceptions to this rule, for example, a few low grade tumors displayed high MiB-1 counts while some highly malignant brain tumors failed to display any positive staining for MiB-1, despite having high mitotic counts. This phenomenon was probably due to loss of proliferating antigens. In the MiB-1 positive sections, hot spots with a high mitotic activity could be identified with ease and the abnormal morphology of the tumor nuclei and of the atypical mitoses were highlighted by the contrasting intensily brown staining. In addition, the dividing cell type could be easily identified and differences in mitotic behavior of invasive and necrotic parts of tumors could be observed. PMID:8835134

  3. Stereotactic iodine-125 brachytherapy for brain tumors: temporary versus permanent implantation.

    PubMed

    Ruge, Maximilian I; Kickingereder, Philipp; Grau, Stefan; Treuer, Harald; Sturm, Volker; Voges, Juergen

    2012-01-01

    Stereotactic brachytherapy (SBT) has been described in several publications as an effective, minimal invasive and safe highly focal treatment option in selected patients with well circumscribed brain tumors <4 cm. However, a still ongoing discussion about indications and technique is hindering the definition of a clear legitimation of SBT in modern brain tumor treatment. These controversies encompass the question of how intense the irradiation should be delivered into the target volume (dose rate). For instance, reports about the use of high does rate (HDR) implantation schemes (>40 cGy/h) in combination with adjuvant external beam radiation and/or chemotherapy for the treatment of malignant gliomas and metastases resulted in increased rates of radiation induced adverse tissue changes requiring surgical intervention. Vice versa, such effects have been only minimally observed in numerous studies applying low dose rate (LDR) regiments (3-8 cGy/h) for low grade gliomas, metastases and other rare indications. Besides these observations, there are, however, no data available directly comparing the long term incidences of tissue changes after HDR and LDR and there is, furthermore, no evidence regarding a difference between temporary or permanent LDR implantation schemes. Thus, recommendations for effective and safe implantation schemes have to be investigated and compared in future studies. PMID:22713629

  4. Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS

    ClinicalTrials.gov

    2016-07-08

    Brain Injury; Central Nervous System Degenerative Disorder; Central Nervous System Infectious Disorder; Central Nervous System Vascular Malformation; Hemorrhagic Cerebrovascular Accident; Ischemic Cerebrovascular Accident; Primary Brain Neoplasm; Brain Cancer; Brain Tumors

  5. PDT-induced apoptosis: investigations using two malignant brain tumor models

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar D.; Menzies, Keir; Bisland, Stuart K.; Lin, Annie; Wilson, Brian C.

    2002-06-01

    PDT included necrosis in brain tissue and an intracranial tumor has been quantified for various photosensitizers, and it has been shown to be dependent on the sub-cellular localization of these photosensitizers. In quantifying non- necrotic biological endpoints, such as PDT induced apoptosis, the expression and translation of apoptosis inhibiting or promoting genes is of considerable importance. We studied the susceptibility of two glioblastoma cell lines to under go apoptotic cell death following photodynamic treatment with either Photofrin or delta-aminolevulinic acid (delta) ALA) in vivo. Murine 9L Gliosarcoma cells or human U87 Glioblastoma cells were implanted into the cortex of rats, and following 12 or 14 days of growth respectively, subjected to either Photofrin-mediated PDT or ALA-mediated PDT. 9L gliosarcoma cells express the phosphatase Tensin homologue (PTEN) tumor suppressor gene while in U87 cells PTEN is mutated. Differences in the Photofrin mediated PDT induced apoptosis were noted between the two different cell lines in vivo, suggesting that Photofrin mediated PDT may be dependent on apoptotic pathways. ALA induced PPIX showed higher selectivity towards 9L than Photofrin mediated PDT. These studies suggests that PDT could be used as an effective treatment for intracranial neoplasm. Endogenous photosensitizers such as ALA could be used to promote apoptosis in tumor cells due to PDT treatment and thereby minimize the extent of necrotic infarction in the surrounding normal brain.

  6. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors. Technical progress report No. 1, May 1, 1990--January 31, 1991

    SciTech Connect

    Soloway, A.H.; Barth, R.F.

    1990-12-31

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  7. Protective effects of some creatine derivatives in brain tissue anoxia.

    PubMed

    Perasso, Luisa; Lunardi, Gian Luigi; Risso, Federica; Pohvozcheva, Anna V; Leko, Maria V; Gandolfo, Carlo; Florio, Tullio; Cupello, Aroldo; Burov, Sergey V; Balestrino, Maurizio

    2008-05-01

    Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocreatine-Mg-complex (acetate) increased the latency to population spike disappearance during anoxia. Creatine and creatine-Mg-complex (acetate) also increased the latency of anoxic depolarization, while the delay induced by phosphocreatine-Mg-complex (acetate) was of borderline significance (P = 0.056). Phosphocreatine-Mg-complex (acetate) significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself) showed. For all parameters except reduced hyperexcitability the effects statistically correlated with tissue levels of creatine or phosphocreatine. Summing up, exogenous phosphocreatine and N-amidino piperidine are not useful for brain protection, while chelates of both creatine and phosphocreatine do replicate some of the known protective effects of creatine. In addition, phosphocreatine-Mg-complex (acetate) also reduced neuronal hyperexcitability during anoxia. PMID:17940889

  8. Diffusion MRI at 25: Exploring brain tissue structure and function

    PubMed Central

    Bihan, Denis Le; Johansen-Berg, Heidi

    2013-01-01

    Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state. PMID:22120012

  9. Memoirs of an amnesiac--two years with brain cancer, or the outer space of living with brain tumors.

    PubMed

    Dor-Ner, A D

    1991-11-01

    Alexandra Dane Dor-Ner ("Ali" to friends) was a photographer, writer, and a producer of programs on child development. In February 1989, at the age of 41, she was diagnosed with malignant brain cancer. During the following months she underwent brain surgery, radiation, and implant radiation. Throughout her treatment, she continued to work on a novel and write stores and literary criticism. A volunteer in hospitals before her illness, she now became very active in a support group of brain tumor patients and often served as a first resource and contact for others diagnosed with brain cancer. All was very accomplished; her award-winning photographs have been exhibited in the Smithsonian Institution in Washington, and her articles and pictures were published in books, periodicals, and newspapers around the world. A native of Boston, Ali lived for 17 years in Israel, where she joined a group of photographers documenting disappearing neighborhoods in Jerusalem. She was awarded first prize in the "Israel Through the Camera's Eye" competition in 1977. She also taught English and photography in Israeli high schools. Ali traveled extensively on photographic assignments. Early in their 22-year marriage, she and her husband circumnavigated the globe on a freighter, producing a documentary film of the voyage. "Memoirs of an Amnesiac" was written while Ali was a student at the Warren Wilson College Writers' Program in North Carolina; she intended to explore the compensatory aspects of her disease. In February 1991, within days of completing the piece, Ali had a third brain operation to remove a regrowth of cancerous tumor cells, as well as necrotic tissue. Two days later, she was again operated on to remove blood clots resulting from the previous surgery. For the next 12 weeks she fought to regain her ability to walk, talk, and write. In May, she underwent a fifth operation to relieve pressure in the brain. She was still in the hospital when she learned, to her great pleasure

  10. Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve.

    PubMed

    Davey, P G; Charter, M; Kelly, S; Varma, T R; Jacobson, I; Freeman, A; Precious, E; Lambert, J

    1994-06-01

    Patients undergoing elective surgery for removal of brain tumors, aneurysms, or other vascular malformations were administered a single oral dose of sparfloxacin (400 mg; 16 patients) or ciprofloxacin (750 mg; 5 patients