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Sample records for brain tumors developpements

  1. 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 ...

  2. 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

  3. 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 ...

  4. 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 ...

  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. 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 ...

  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. 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 ...

  9. 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 ...

  10. 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, ...

  11. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... Cancer Foundation joins the PBTF Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  12. American Brain Tumor Association

    MedlinePlus

    ... in the Ear Canals Read More ABTA News October 5, 2016 Largest American Brain Tumor Association Team Running in Bank of America Chicago Marathon Sunday, October 9 September 21, 2016 American Brain Tumor Association Awards 16 Grants to Support ...

  13. 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 ...

  14. Brain tumor - primary - adults

    MedlinePlus

    ... tumor, relieve symptoms, and improve brain function or comfort. Surgery is often needed for most primary brain ... and pressure Anticonvulsants to reduce seizures Pain medicines Comfort measures, safety measures, physical therapy, and occupational therapy ...

  15. Brain tumor - children

    MedlinePlus

    ... symptoms, and improve brain function or the child's comfort. Surgery is needed for most primary brain tumors. ... Anticonvulsants to reduce or prevent seizures Pain medicines Comfort measures, safety measures, physical therapy, occupational therapy, and ...

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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) ...

  1. 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

  2. [Chemotherapy of brain tumors].

    PubMed

    Kuratsu, J; Ushio, Y

    1994-10-01

    Despite recent attempts to improve chemotherapeutic approaches for the treatment of malignant gliomas, results remain limited and palliative. The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (B.B.B.) hampers the penetration of most drugs into the brain and cerebrospinal fluid. The factors governing delivery in the brain are the drug's molecular weight, lipophilicity and degree of ionization. Now the standard therapy for malignant glioma is maximal tumor resection followed by combination radiotherapy plus chemotherapy. Nitrosoureas are representative drugs which easily cross the B.B.B.. It has been shown that nitrosourea compounds have an additive effect to radiotherapy. The toxicity profile of nitrosoureas is leukocytopenia and thrombocytopenia as a dose-limiting factor. Furthermore, the great heterogeneity of malignant glioma tissues offered a rationale for the use of multiple drugs. Many studies were reported to show a substantial advantage for the multidrug regimen over control series utilizing single drugs alone. Despite clear examples of the effectiveness of chemotherapy, we are still far from improving the cure rate for the vast majority of patients with primary malignancies of the CNS. Further improvement in patient survival may depend upon understanding and manipulating the pathways that regulate aberrant growth in these tumors. The development of new anticancer agents, which are sensitive to malignant glioma and can reach a high concentration in glioma tissue, is warranted. PMID:7986118

  3. 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.

  4. 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

  5. Pediatric brain tumors and epilepsy.

    PubMed

    Wells, Elizabeth M; Gaillard, William D; Packer, Roger J

    2012-03-01

    Seizures are a common complication of pediatric brain tumors and their treatment. This article reviews the epidemiology, evaluation, and treatment of seizures in children with brain tumors. Seizures in known brain tumor patients may signify tumor progression or recurrence, or treatment-related brain damage, as well as other causes, including low drug levels and metabolic disturbances. Careful selection of antiepileptic medications is needed in this population. There are advantages to nonenzyme-inducing antiepileptic drugs including valproic acid, which has potential antitumoral properties as a histone deacetylase inhibitor. Tumor surgery cures many cases of pediatric tumor-associated seizures, and some children are controlled with anti-epileptic medication, however additional epilepsy surgery may be needed for refractory cases.

  6. 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

  7. 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

  8. 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 ...

  9. Metastatic brain tumor

    MedlinePlus

    ... be to relieve symptoms, improve functioning, or provide comfort. Radiation to the whole brain is often used ... symptoms. This is called palliative or supportive care. Comfort measures, safety measures, physical therapy, occupational therapy, and ...

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Gene therapy for brain tumors.

    PubMed

    Bansal, K; Engelhard, H H

    2000-09-01

    "Gene therapy" can be defined as the transfer of genetic material into a patient's cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug ("suicide gene") therapy, oncolytic therapy, replacement/therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.

  15. What underlies the diversity of brain tumors?

    PubMed Central

    Swartling, Fredrik J.; Hede, Sanna-Maria; Weiss, William A.

    2012-01-01

    Glioma and medulloblastoma represent the most commonly occurring malignant brain tumors in adults and in children respectively. Recent genomic and transcriptional approaches present a complex group of diseases, and delineate a number of molecular subgroups within tumors that share a common histopathology. Differences in cells of origin, regional niches, developmental timing and genetic events all contribute to this heterogeneity. In an attempt to recapitulate the diversity of brain tumors, an increasing array of genetically engineered mouse models (GEMMs) has been developed. These models often utilize promoters and genetic drivers from normal brain development, and can provide insight into specific cells from which these tumors originate. GEMMs show promise in both developmental biology and developmental therapeutics. This review describes numerous murine brain tumor models in the context of normal brain development, and the potential for these animals to impact brain tumor research. PMID:23085857

  16. Brain angiogenesis: Mechanism and Therapeutic Intervention in Brain Tumors

    PubMed Central

    Kim, Woo-Young; Lee, Ho-Young

    2010-01-01

    Summary Formation of new blood vessels is required for growth and metastasis of all solid tumors. New blood vessels are established in tumors mainly through angiogenesis. Brain tumors in particular are highly angiogenic. Therefore, interventions designed to prevent angiogenesis may be effective at controlling brain tumors. Indeed, many recent findings from preclinical and clinical studies of antiangiogenic therapy for brain tumors showed that it is a promising approach to managing this deadly disease, especially when combined with other cytotoxic treatments. In this review, we summarize the basic characteristics of brain tumor angiogenesis and role of known angiogenic factors in regulating this angiogenesis, which can be targets of antiangiogenic therapy. We also discuss the current status of antiangiogenic therapy for brain tumors, the suggested mechanisms of this therapy, and the limitations of this strategy. PMID:19664069

  17. 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.

  18. 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 ...

  19. 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

  20. 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

  1. 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 ...

  2. Three mutant genes cooperatively induce brain tumor formation in Drosophila malignant brain tumor.

    PubMed

    Riede, I

    1996-09-01

    The Drosophila melanogaster strain Malignant Brain Tumor reveals temperature-sensitive transformation of the larval brain tissue. Genetic analysis shows that three gene defects, spzMBT, yetiMBT, and tldMBT, cooperatively induce brain tumor formation. Whereas spz and tld belong to the genes inducing differentiation patterns in the embryo, yeti induces cell overgrowth. spzMBT-, yetiMBT-, and tldMBT-containing animals are larval lethal, whereas Malignant Brain Tumor is kept as a homozygous strain at a permissive temperature. This reveals that this tumor-forming strain is the result of a number of adaptive mutation events.

  3. Surgical Outcomes of Hemorrhagic Metastatic Brain Tumors

    PubMed Central

    Yoo, Heon; Jung, Eugene; Gwak, Ho Shin; Shin, Sang Hoon

    2011-01-01

    Purpose Hemorrhagic metastatic brain tumors are not rare, but little is known about the surgical outcome following treatment. We conducted this study to determine the result of the surgical outcome of hemorrhagic metastatic brain tumors. Materials and Methods From July 2001 to December 2008, 21 patients underwent surgery for hemorrhagic metastatic brain tumors at our institution. 15 patients had lung cancer, 3 had hepatocellular carcinoma, and the rest had rectal cancer, renal cell carcinoma, and sarcoma. 20 patients had macroscopic hemorrhage in the tumors, and one patient had intracerebral hemorrhage surrounding the tumor. A retrospective clinical review was conducted focusing on the patterns of presenting symptoms and signs, as well as local recurrence following surgery. Results Among 21 hemorrhagic brain metastases, local recurrence developed in two patients. The 12 month progression free survival rate was 86.1%. Mean time to progression was 20.8 months and median survival time after surgery was 11.7 months. Conclusion The results of our study showed that hemorrhagic metastatic brain tumors rarely recurred after surgery. Surgery should be considered as a good treatment option for hemorrhagic brain metastasis, especially in cases with increased intracranial pressure or severe neurologic deficits. PMID:21811426

  4. Brain tumor immunotherapy: an immunologist's perspective.

    PubMed

    Lampson, Lois A

    2003-01-01

    Key concepts in brain tumor immunotherapy are reviewed. "Immunotherapy" can refer to a fully-developed, tumor-specific immune response, or to its individual cellular or molecular mediators. The immune response is initiated most efficiently in organized lymphoid tissue. After initiation, antigen-specific T lymphocytes (T cells) survey the tissues--including the brain. If the T cells re-encounter their antigen at a tumor site, they can be triggered to carry out their effector functions. T cells can attack tumor in many ways, directly and indirectly, through cell-cell contact, secreted factors, and attraction and activation of other cells, endogenous or blood-borne. Recent work expands the list of candidate tumor antigens: they are not limited to cell surface proteins and need not be absolutely tumor-specific. Once identified, tumor antigens can be targeted immunologically, or in novel ways. The immune response is under complex regulatory control. Most current work aims to enhance initiation of the response (for example, with tumor vaccines), rather than enhancing the effector phase at the tumor site. The effector phase includes a rich, interactive set of cells and mediators; some that are not usually stressed are of particular interest against tumor in the brain. Within the brain, immune regulation varies from site to site, and local neurochemicals (such as substance P or glutamate) can contribute to local control. Given the complexity of a tumor, the brain, and the immune response, animal models are essential, but more emphasis should be given to their limitations and to step-by-step analysis, rather than animal "cures".

  5. Oncogenic extracellular vesicles in brain tumor progression.

    PubMed

    D'Asti, Esterina; Garnier, Delphine; Lee, Tae H; Montermini, Laura; Meehan, Brian; Rak, Janusz

    2012-01-01

    The brain is a frequent site of neoplastic growth, including both primary and metastatic tumors. The clinical intractability of many brain tumors and their distinct biology are implicitly linked to the unique microenvironment of the central nervous system (CNS) and cellular interactions within. Among the most intriguing forms of cellular interactions is that mediated by membrane-derived extracellular vesicles (EVs). Their biogenesis (vesiculation) and uptake by recipient cells serves as a unique mechanism of intercellular trafficking of complex biological messages including the exchange of molecules that cannot be released through classical secretory pathways, or that are prone to extracellular degradation. Tumor cells produce EVs containing molecular effectors of several cancer-related processes such as growth, invasion, drug resistance, angiogenesis, and coagulopathy. Notably, tumor-derived EVs (oncosomes) also contain oncogenic proteins, transcripts, DNA, and microRNA (miR). Uptake of this material may change properties of the recipient cells and impact the tumor microenvironment. Examples of transformation-related molecules found in the cargo of tumor-derived EVs include the oncogenic epidermal growth factor receptor (EGFRvIII), tumor suppressors (PTEN), and oncomirs (miR-520g). It is postulated that EVs circulating in blood or cerebrospinal fluid (CSF) of brain tumor patients may be used to decipher molecular features (mutations) of the underlying malignancy, reflect responses to therapy, or molecular subtypes of primary brain tumors [e.g., glioma or medulloblastoma (MB)]. It is possible that metastases to the brain may also emit EVs with clinically relevant oncogenic signatures. Thus, EVs emerge as a novel and functionally important vehicle of intercellular communication that can mediate multiple biological effects. In addition, they provide a unique platform to develop molecular biomarkers in brain malignancies. PMID:22934045

  6. 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) ...

  7. 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

  8. [A unusual brain cortical tumor: angiocentric glioma].

    PubMed

    Tauziède-Espariat, Arnault; Fohlen, Martine; Ferrand-Sorbets, Sarah; Polivka, Marc

    2015-04-01

    We report the case of an 11-year-old girl, who was admitted for surgery of an epilepsy-associated brain tumor. The radiological and clinical hypothesis was dysembryoplasic neuroepithelial tumor. Histopathological examination revealed a tumoral proliferation composed of spindle-shaped cells with palisade arrangements around vessels. Tumor cells have small, round and regular nuclei without atypia or mitosis. On immunohistochemistry, the neoplastic cells strongly expressed GFAP and showed a characteristic cytoplasmic dot-like staining with EMA (epithelial membrane antigen). Ki-67 labeling index was low. Molecular analysis failed to reveal the V600E mutation of BRAF gene. The patient was free of seizures after surgery. Angiocentric glioma is a rare brain tumor occuring preferably in children and young adults and is associated with seizures. The precise histogenesis remains debated. The treatment of choice is total resection. The prognosis is favorable if totally resected.

  9. 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).

  10. 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.

  11. 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

  12. Head, neck, and brain tumor embolization guidelines

    PubMed Central

    Duffis, E Jesus; Prestigiacomo, Charles Joseph; Abruzzo, Todd; Albuquerque, Felipe; Bulsara, Ketan R; Derdeyn, Colin P; Fraser, Justin F; Hirsch, Joshua A; Hussain, Muhammad Shazam; Do, Huy M; Jayaraman, Mahesh V; Meyers, Philip M; Narayanan, Sandra

    2012-01-01

    Background Management of vascular tumors of the head, neck, and brain is often complex and requires a multidisciplinary approach. Peri-operative embolization of vascular tumors may help to reduce intra-operative bleeding and operative times and have thus become an integral part of the management of these tumors. Advances in catheter and non-catheter based techniques in conjunction with the growing field of neurointerventional surgery is likely to expand the number of peri-operative embolizations performed. The goal of this article is to provide consensus reporting standards and guidelines for embolization treatment of vascular head, neck, and brain tumors. Summary This article was produced by a writing group comprised of members of the Society of Neurointerventional Surgery. A computerized literature search using the National Library of Medicine database (Pubmed) was conducted for relevant articles published between 1 January 1990 and 31 December 2010. The article summarizes the effectiveness and safety of peri-operative vascular tumor embolization. In addition, this document provides consensus definitions and reporting standards as well as guidelines not intended to represent the standard of care, but rather to provide uniformity in subsequent trials and studies involving embolization of vascular head and neck as well as brain tumors. Conclusions Peri-operative embolization of vascular head, neck, and brain tumors is an effective and safe adjuvant to surgical resection. Major complications reported in the literature are rare when these procedures are performed by operators with appropriate training and knowledge of the relevant vascular and surgical anatomy. These standards may help to standardize reporting and publication in future studies. PMID:22539531

  13. [Conformal radiotherapy of brain tumors].

    PubMed

    Haie-Meder, C; Beaudré, A; Breton, C; Biron, B; Cordova, A; Dubray, B; Mazeron, J J

    1999-01-01

    Conformal irradiation of brain tumours is based on the three-dimensional reconstruction of the targeted volumes and at-risk organ images, the three-dimensional calculation of the dose distribution and a treatment device (immobilisation, beam energy, collimation, etc.) adapted to the high precision required by the procedure. Each step requires an appropriate methodology and a quality insurance program. Specific difficulties in brain tumour management are related to GTV and CTV definition depending upon the histological type, the quality of the surgical resection and the medical team. Clinical studies have reported dose escalation trials, mostly in high-grade gliomas and tumours at the base of the skull. Clinical data are now providing a better knowledge of the tolerance of normal tissues. As for small tumours, the implementation of beam intensity modulation is likely to narrow the gap between conformal and stereotaxic radiotherapy. PMID:10572510

  14. The delivery of BCNU to brain tumors.

    PubMed

    Wang, C C; Li, J; Teo, C S; Lee, T

    1999-08-27

    This paper reports the development of three-dimensional simulations to study the effect of various factors on the delivery of 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to brain tumors. The study yields information on the efficacy of various delivery methods, and the optimal location of polymer implantation. Two types of drug deliveries, namely, systemic administration and controlled release from polymers, were simulated using fluid dynamics analysis package (FIDAP) to predict the temporal and spatial variation of drug distribution. Polymer-based delivery provides higher mean concentration, longer BCNU exposure time and reduced systemic toxicity than bolus injection. Polymer implanted in the core gives higher concentration of drug in both the core and viable zone than the polymer in the viable zone case. The penetration depth of BCNU is very short. This is because BCNU can get drained out of the system before diffusing to any appreciable distance. Since transvascular permeation is the dominant means of BCNU delivery, the interstitial convection has minor effect because of the extremely small transvascular Peclet number. The reaction of BCNU with brain tissues reduces the drug concentration in all regions and its effect increases with rate constant. The implantation of BCNU/ethylene-vinyl acetate copolymer (EVAc) matrix at the lumen of the viable zone immediately following the surgical removal of 80% of the tumor may be an effective treatment for the chemotherapy of brain tumors. The present study provides a quantitative examination on the working principle of Gliadel wafer for the treatment of brain tumors.

  15. [Differential infratentorial brain tumor diagnosis in children].

    PubMed

    Warmuth-Metz, M; Kühl, J; Rutkowski, S; Krauss, J; Solymosi, L

    2003-11-01

    With the exception of the first year of life, infratentorial brain tumors are more frequent in the first decade than tumors in the supratentorial compartment. In particular these are cerebellar low-grade astrocytomas, medulloblastomas, brainstem gliomas and ependymomas of the fourth ventricle. The morphology on MRI and CT and the mode of dissemination permit differential diagnosis in many cases. To allow correct stratification into different treatments in possibly disseminating malignant brain tumors, knowledge of the status of dissemination is essential, and therefore not only cranial but also spinal MRI is indispensable for staging. If the spinal MRI is performed in the immediate postoperative period, knowledge of the normal non-specific purely postoperative changes, often seen as enhancement in the subdural spinal spaces, is necessary in order to avoid misinterpretation as meningial seeding. The differential diagnosis of pediatric infratentorial brain tumors and the morphology of subdural enhancement are illustrated with typical images. The natural history of the most frequent tumors and its importance for treatment decisions is discussed in light of the literature.

  16. A Rare Malignant Fetal Brain Tumor.

    PubMed

    Iruretagoyena, Jesus Igor; Heiser, Timothy; Iskandar, Bermans; Shah, Dinesh

    2016-01-01

    A gravida 4, para 3 female at 37 weeks' gestation presented for a routine ultrasound. She had an otherwise uncomplicated low-risk pregnancy. The sonographic evaluation of the fetus revealed a macrocephaly and a deviation of the brain midline structures with a mass effect as well as a massively dilated left cerebral ventricular system with ill-defined echogenic ventricular delineation. Multiple free intracavitary echogenicities and disruptions of the brain mantle were visible. Our images were suggestive of either an intracranial bleed with the presence of an underlying tumor or a spontaneous bleed. A postnatal MRI was consistent with our prenatal findings of a possible tumor. The postnatal biopsy revealed an anaplastic astroblastoma within a hemorrhagic background. The infant received multiple courses of chemotherapy and further tumor debulking. At present, the infant is 18 months old. This is only the 4th case of an astrocytoma identified in the fetal period, and our case has the longest known survival yet. PMID:26044034

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    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

  3. 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

  4. 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.

  5. 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)

  6. 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

  7. Photodynamic therapy for implanted VX2 tumor in rabbit brains

    NASA Astrophysics Data System (ADS)

    Li, Fei; Feng, Hua; Lin, Jiangkai; Zhu, Gang; Chen, Zhi; Li, Cong-yan

    2005-07-01

    To evaluate the therapeutic effect and the safety of single photodynamic therapy (PDT) with hematoporphyrin derivative produced in China, 60 New Zealand adult rabbits with VX2 tumor implanted into the brain were divided randomly into non-PDT-group and PDT-group. 36 rabbits of the PDT-group were performed photodynamic therapy. The survival time, neurological deteriorations, intracranial pressure (ICP), histology, pathology, tumor volume and brain water content were measured. Other 12 rabbits were received hematoporphyrin derivative and light irradiation of the normal brain. The ICP, histology, pathology, and brain water content were measured. The result indicated that Simple PDT may elongate the average survival time of the rabbits with VX2 tumors significantly; kill tumor cells; cause transient brain edema and increase ICP, but it is safe to be used in treating brain tumor.

  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. Brain tumor resection guided by fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Leblond, Frederic; Fontaine, Kathryn M.; Valdes, Pablo; Ji, Songbai; Pogue, Brian W.; Hartov, Alex; Roberts, David W.; Paulsen, Keith D.

    2009-02-01

    We present the methods that are being used in the scope of an on-going clinical trial designed to assess the usefulness of ALA-PpIX fluorescence imaging when used in conjunction with pre-operative MRI. The overall objective is to develop imaging-based neuronavigation approaches to aid in maximizing the completeness of brain tumor resection, thereby improving patient survival rate. In this paper we present the imaging methods that are used, emphasizing technical aspects relating to the fluorescence optical microscope, including initial validation approaches based on phantom and small-animal experiments. The surgical workflow is then described in detail based on a high-grade glioma resection we performed.

  10. Increasing brain tumor rates: is there a link to aspartame?

    PubMed

    Olney, J W; Farber, N B; Spitznagel, E; Robins, L N

    1996-11-01

    In the past two decades brain tumor rates have risen in several industrialized countries, including the United States. During this time, brain tumor data have been gathered by the National Cancer Institute from catchment areas representing 10% of the United States population. In the present study, we analyzed these data from 1975 to 1992 and found that the brain tumor increases in the United States occurred in two distinct phases, an early modest increase that may primarily reflect improved diagnostic technology, and a more recent sustained increase in the incidence and shift toward greater malignancy that must be explained by some other factor(s). Compared to other environmental factors putatively linked to brain tumors, the artificial sweetener aspartame is a promising candidate to explain the recent increase in incidence and degree of malignancy of brain tumors. Evidence potentially implicating aspartame includes an early animal study revealing an exceedingly high incidence of brain tumors in aspartame-fed rats compared to no brain tumors in concurrent controls, the recent finding that the aspartame molecule has mutagenic potential, and the close temporal association (aspartame was introduced into US food and beverage markets several years prior to the sharp increase in brain tumor incidence and malignancy). We conclude that there is need for reassessing the carcinogenic potential of aspartame.

  11. 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

  12. 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

  13. Lassa-Vesicular Stomatitis Chimeric Virus Safely Destroys Brain Tumors

    PubMed Central

    Wollmann, Guido; Drokhlyansky, Eugene; Davis, John N.; Cepko, Connie

    2015-01-01

    ABSTRACT High-grade tumors in the brain are among the deadliest of cancers. Here, we took a promising oncolytic virus, vesicular stomatitis virus (VSV), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic VSV glycoprotein with the glycoprotein from one of five different viruses, including Ebola virus, Marburg virus, lymphocytic choriomeningitis virus (LCMV), rabies virus, and Lassa virus. Based on in vitro infections of normal and tumor cells, we selected two viruses to test in vivo. Wild-type VSV was lethal when injected directly into the brain. In contrast, a novel chimeric virus (VSV-LASV-GPC) containing genes from both the Lassa virus glycoprotein precursor (GPC) and VSV showed no adverse actions within or outside the brain and targeted and completely destroyed brain cancer, including high-grade glioblastoma and melanoma, even in metastatic cancer models. When mice had two brain tumors, intratumoral VSV-LASV-GPC injection in one tumor (glioma or melanoma) led to complete tumor destruction; importantly, the virus moved contralaterally within the brain to selectively infect the second noninjected tumor. A chimeric virus combining VSV genes with the gene coding for the Ebola virus glycoprotein was safe in the brain and also selectively targeted brain tumors but was substantially less effective in destroying brain tumors and prolonging survival of tumor-bearing mice. A tropism for multiple cancer types combined with an exquisite tumor specificity opens a new door to widespread application of VSV-LASV-GPC as a safe and efficacious oncolytic chimeric virus within the brain. IMPORTANCE Many viruses have been tested for their ability to target and kill cancer cells. Vesicular stomatitis virus (VSV) has shown substantial promise, but a key problem is that if it enters the brain, it can generate adverse neurologic consequences, including death. We

  14. Patients With Brain Tumors: Who Receives Postacute Occupational Therapy Services?

    PubMed

    Chan, Vincy; Xiong, Chen; Colantonio, Angela

    2015-01-01

    Data on the utilization of occupational therapy among patients with brain tumors have been limited to those with malignant tumors and small samples of patients outside North America in specialized palliative care settings. We built on this research by examining the characteristics of patients with brain tumors who received postacute occupational therapy services in Ontario, Canada, using health care administrative data. Between fiscal years 2004-2005 and 2008-2009, 3,199 patients with brain tumors received occupational therapy services in the home care setting after hospital discharge; 12.4% had benign brain tumors, 78.2% had malignant brain tumors, and 9.4% had unspecified brain tumors. However, patients with benign brain tumors were older (mean age=63.3 yr), and a higher percentage were female (65.2%). More than 90% of patients received in-home occupational therapy services. Additional research is needed to examine the significance of these differences and to identify factors that influence access to occupational therapy services in the home care setting.

  15. Multifractal texture estimation for detection and segmentation of brain tumors.

    PubMed

    Islam, Atiq; Reza, Syed M S; Iftekharuddin, Khan M

    2013-11-01

    A stochastic model for characterizing tumor texture in brain magnetic resonance (MR) images is proposed. The efficacy of the model is demonstrated in patient-independent brain tumor texture feature extraction and tumor segmentation in magnetic resonance images (MRIs). Due to complex appearance in MRI, brain tumor texture is formulated using a multiresolution-fractal model known as multifractional Brownian motion (mBm). Detailed mathematical derivation for mBm model and corresponding novel algorithm to extract spatially varying multifractal features are proposed. A multifractal feature-based brain tumor segmentation method is developed next. To evaluate efficacy, tumor segmentation performance using proposed multifractal feature is compared with that using Gabor-like multiscale texton feature. Furthermore, novel patient-independent tumor segmentation scheme is proposed by extending the well-known AdaBoost algorithm. The modification of AdaBoost algorithm involves assigning weights to component classifiers based on their ability to classify difficult samples and confidence in such classification. Experimental results for 14 patients with over 300 MRIs show the efficacy of the proposed technique in automatic segmentation of tumors in brain MRIs. Finally, comparison with other state-of-the art brain tumor segmentation works with publicly available low-grade glioma BRATS2012 dataset show that our segmentation results are more consistent and on the average outperforms these methods for the patients where ground truth is made available. PMID:23807424

  16. Distinctive responses of brain tumor cells to TLR2 ligands.

    PubMed

    Yoon, Hee Jung; Jeon, Sae-Bom; Koh, Han Seok; Song, Jae-Young; Kim, Sang Soo; Kim, In-Hoo; Park, Eun Jung

    2015-05-01

    Malignant brain tumor mass contains significant numbers of infiltrating glial cells that may intimately interact with tumor cells and influence cancer treatments. Understanding of characteristic discrepancies between normal GLIA and tumor cells would, therefore, be valuable for improving anticancer therapeutics. Here, we report distinct differences in toll-like receptors (TLR)-2-mediated responses between normal glia and primary brain tumor cell lines. We found that tyrosine phosphorylation of STAT1 by TLR2 ligands and its downstream events did not occur in mouse, rat, or human brain tumor cell lines, but were markedly induced in normal primary microglia and astrocytes. Using TLR2-deficient, interferon (IFN)-γ-deficient, and IFNγ-receptor-1-deficient mice, we revealed that the impaired phosphorylation of STAT1 might be linked with defective TLR2 system in tumor cells, and that a TLR2-dependent pathway, not IFNγ-receptor machinery, might be critical for tyrosine STAT1 phosphorylation by TLR2 ligands. We also found that TLR2 and its heterodimeric partners, TLR1 and 6, on brain tumor cells failed to properly respond to TLR2 ligands, and representative TLR2-dependent cellular events, such as inflammatory responses and cell death, were not detected in brain tumor cells. Similar results were obtained in in vitro and in vivo experiments using orthotopic mouse and rat brain tumor models. Collectively, these results suggest that primary brain tumor cells may exhibit a distinctive dysfunction of TLR2-associated responses, resulting in abnormal signaling and cellular events. Careful targeting of this distinctive property could serve as the basis for effective therapeutic approaches against primary brain tumors.

  17. Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

    SciTech Connect

    Yuan Jiankui; Wang, Jian Z. Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

    2008-10-01

    Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The {alpha}/{beta} ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible {alpha}/{beta} ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens.

  18. Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

    PubMed

    Fontebasso, Adam M; Jabado, Nada

    2015-01-01

    Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

  19. 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

  20. 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

  1. Computational modeling of brain tumors: discrete, continuum or hybrid?

    NASA Astrophysics Data System (ADS)

    Wang, Zhihui; Deisboeck, Thomas S.

    In spite of all efforts, patients diagnosed with highly malignant brain tumors (gliomas), continue to face a grim prognosis. Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models have the potential to provide experimental tumor biologists with such quantitative and cost-efficient tools to generate and test hypotheses on tumor progression, and to infer fundamental operating principles governing bidirectional signal propagation in multicellular cancer systems. This review highlights the modeling objectives of and challenges with developing such in silico brain tumor models by outlining two distinct computational approaches: discrete and continuum, each with representative examples. Future directions of this integrative computational neuro-oncology field, such as hybrid multiscale multiresolution modeling are discussed.

  2. Radiosurgery-induced brain tumor. Case report.

    PubMed

    Kaido, T; Hoshida, T; Uranishi, R; Akita, N; Kotani, A; Nishi, N; Sakaki, T

    2001-10-01

    The authors describe a case of glioblastoma multiforme (GBM) associated with previous gamma knife radiosurgery for a cerebral arteriovenous malformation (AVM). A 14-year-old boy had undergone radiosurgery for an AVM, which was performed using a 201-source 60Co gamma knife system at another institution. The maximum and margin radiation doses used in the procedure were 40 and 20 Gy, respectively. One year after radiosurgery, the patient noticed onset of mild left hemiparesis due to radiation necrosis. Six and one-half years after radiosurgery, at the age of 20 years, the patient experienced an attack of generalized tonic-clonic seizure. Magnetic resonance (MR) imaging revealed the existence of a brain tumor in the right parietal lobe. The patient underwent an operation and the histological diagnosis of the lesion was GBM. Ten months following the operation, that is, 99 months postradiosurgery, this patient died. To the best of the authors' knowledge, this is the first reported case of a neoplasm induced by radiosurgery for an AVM and the second case in which it occurred following radiosurgery for intracranial disease.

  3. 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

  4. 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.

  5. 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 ...

  6. 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 ...

  7. [Tumor Cells and Micro-environment in Brain Metastases].

    PubMed

    Zhong, Wen; Hu, Chengping

    2016-09-20

    Improvements in survival and quality of life of patients with lung cancer had been achieved due to the progression of early diagnosis and precision medicine at recent years, however, until now, treatments targeted at lesions in central nervous system are far from satisfying, thus threatening livelihood of patients involved. After all, in the issue of prophylaxis and therapeutics of brain metastases, it is crucial to learn about the biological behavior of tumor cells in brain metastases and its mechanism underlying, and the hypothesis "seed and soil", that is, tumor cells would generate series of adaptive changes to fit in the new environment, is liable to help explain this process well. In this assay, we reviewed documents concerning tumor cells, brain micro-environments and their interactions in brain metastases, aiming to provide novel insight into the treatments of brain metastases. PMID:27666556

  8. 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

  9. Automated segmentation of MR images of brain tumors.

    PubMed

    Kaus, M R; Warfield, S K; Nabavi, A; Black, P M; Jolesz, F A; Kikinis, R

    2001-02-01

    An automated brain tumor segmentation method was developed and validated against manual segmentation with three-dimensional magnetic resonance images in 20 patients with meningiomas and low-grade gliomas. The automated method (operator time, 5-10 minutes) allowed rapid identification of brain and tumor tissue with an accuracy and reproducibility comparable to those of manual segmentation (operator time, 3-5 hours), making automated segmentation practical for low-grade gliomas and meningiomas. PMID:11161183

  10. Radiation therapy options for management of the brain tumor patient.

    PubMed

    Lamb, S A

    1995-03-01

    Radiation therapy rarely cures malignant brain tumors; however, it is the best treatment available at present. Refinement of radiation delivery systems must continue in order to minimize normal tissue injury and to maximize the quality of life. Multimodal therapy designed to attack cancer at its genetic makeup holds great promise. Radiation therapy will always remain one of the forms of therapy used to treat malignant brain tumors.

  11. FDTD analysis of a noninvasive hyperthermia system for brain tumors

    PubMed Central

    2012-01-01

    Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors. PMID:22891953

  12. Emerging insights into barriers to effective brain tumor therapeutics.

    PubMed

    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

  13. 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

  14. 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 ( ...

  15. Infant brain tumors: a neuropathologic population-based institutional reappraisal.

    PubMed

    Dunham, Christopher; Pillai, Shibu; Steinbok, Paul

    2012-10-01

    The factors that impact the long-term functional outcome for infants with brain tumor are unclear. The clinicopathologic features of all infant brain tumors occurring at our institution (1982-2005) were reexamined to explore the factors influencing prognosis. The details of the neuropathologic review are reported herein. Thirty-five cases were identified and included 7 astrocytomas (6 low grade and 1 glioblastoma), 6 atypical teratoid rhabdoid tumors, 5 choroid plexus papillomas, 4 ependymomas (3 anaplastic), 4 teratomas (3 immature), 2 supratentorial primitive neuroectodermal tumors, 2 gangliogliomas, 2 desmoplastic tumors of infancy, and 1 each of "medulloblastoma with extensive nodularity," adamantinomatous craniopharyngioma, and 1 "malignancy not otherwise specified." The original diagnosis was changed in 8 cases (23%), and atypical teratoid rhabdoid tumors was the most common revision (n = 5). Case 9 was unusual in that both the patient and her 2-year-old sister displayed INI-1 immunonegative posterior fossa tumors and extended survival. Tumor grade was altered in 6 cases (17%), the most significant instance being the downgrading from the World Health Organization grade IV to I (case 18: supratentorial primitive neuroectodermal tumors to desmoplastic tumors of infancy). As opposed to other reports in the literature, our cohort contained a substantially higher frequency of atypical teratoid rhabdoid tumors and a lower frequency of medulloblastoma. Changes in the histologic diagnosis/grade in a significant subset of cases most likely reflect the continual evolution of brain tumor classification schemes. INI-1 immunohistochemistry was instrumental in the pathologic assessment of select cases and raised the possibility that atypical teratoid rhabdoid tumors may be the most common infant brain malignancy.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Measles may be a Risk Factor for Malignant Brain Tumors

    PubMed Central

    Green, Sheryl; Rendo, Angela; Rosenzweig, Kenneth E.

    2015-01-01

    Background A possible risk factor for brain tumor might be measles, since late neurologic sequelae are part of measles pathology. Subacute sclerosing panencephalitis, a devastating neurologic illness, is prone to develop years after measles infection. Methods Because measles damage to the brain might increase the risk of brain tumor, we examined the relationship of measles incidence in 1960 and brain tumor incidence in 50 US States and the District of Columbia, 2004-2007. Data on number of cases of measles by state in 1960 are from the Morbidity and Mortality Weekly Report. In 1960 measles was a childhood illness. We calculated measles incidence by obtaining the population of each state from the 1960 US Census and then age adjusting our results to the cumulative percent of the state population under age 21, since this would have been the measles-infected group. Data on the percentage white population by state are from the US Census (www.census.gov). Age-adjusted incidence (to the 2000 US standard population) of brain tumors is from the Central Brain Tumor Registry of the United States 2011 report. Results There was a significant correlation between 1960 measles incidence and incidence of malignant brain tumors in persons 20 and older in 2004-2007 (r=0.321, p=0.026). Because glioblastoma is more frequent in whites and males, multivariate linear regression was performed with tumor incidence as the dependent variable, measles incidence, percent white population, and sex ratio by state as independent variables. Measles incidence was significantly correlated with malignant brain tumor incidence (β=0.361, p<0.001) and independent of the effect of race (β=0.734, p<0.001) and sex ratio m/f (β=-0.478, p<0.001). There was no correlation of measles incidence with brain tumor incidence in persons younger than 20. Conclusion Inflammation is a critical component of tumor development. The inflammation of measles-induced subacute sclerosing panencephalitis, even subclinical

  2. 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

  3. Multiclass feature selection for improved pediatric brain tumor segmentation

    NASA Astrophysics Data System (ADS)

    Ahmed, Shaheen; Iftekharuddin, Khan M.

    2012-03-01

    In our previous work, we showed that fractal-based texture features are effective in detection, segmentation and classification of posterior-fossa (PF) pediatric brain tumor in multimodality MRI. We exploited an information theoretic approach such as Kullback-Leibler Divergence (KLD) for feature selection and ranking different texture features. We further incorporated the feature selection technique with segmentation method such as Expectation Maximization (EM) for segmentation of tumor T and non tumor (NT) tissues. In this work, we extend the two class KLD technique to multiclass for effectively selecting the best features for brain tumor (T), cyst (C) and non tumor (NT). We further obtain segmentation robustness for each tissue types by computing Bay's posterior probabilities and corresponding number of pixels for each tissue segments in MRI patient images. We evaluate improved tumor segmentation robustness using different similarity metric for 5 patients in T1, T2 and FLAIR modalities.

  4. Rapid and automatic detection of brain tumors in MR images

    NASA Astrophysics Data System (ADS)

    Wang, Zhengjia; Hu, Qingmao; Loe, KiaFock; Aziz, Aamer; Nowinski, Wieslaw L.

    2004-04-01

    An algorithm to automatically detect brain tumors in MR images is presented. The key concern is speed in order to process efficiently large brain image databases and provide quick outcomes in clinical setting. The method is based on study of asymmetry of the brain. Tumors cause asymmetry of the brain, so we detect brain tumors in 3D MR images using symmetry analysis of image grey levels with respect to the midsagittal plane (MSP). The MSP, separating the brain into two hemispheres, is extracted using our previously developed algorithm. By removing the background pixels, the normalized grey level histograms are calculated for both hemispheres. The similarity between these two histograms manifests the symmetry of the brain, and it is quantified by using four symmetry measures: correlation coefficient, root mean square error, integral of absolute difference (IAD), and integral of normalized absolute difference (INAD). A quantitative analysis of brain normality based on 42 patients with tumors and 55 normals is presented. The sensitivity and specificity of IAD and INAD were 83.3% and 89.1%, and 85.7% and 83.6%, respectively. The running time for each symmetry measure for a 3D 8bit MR data was between 0.1 - 0.3 seconds on a 2.4GHz CPU PC.

  5. 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

  6. 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.

  7. PDE5 inhibitors enhance tumor permeability and efficacy of chemotherapy in a rat brain tumor model.

    PubMed

    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; Irvin, Dwain K; Shu, Yan

    2008-09-16

    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 (K(Ca)) 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 enhances anti-tumor efficacy for a chemotherapeutic agent. These findings have significant implications for improving delivery of anti-tumor agents to brain tumors. PMID:18674521

  8. 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

  9. 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

  10. Incidence of brain tumors in rats fed aspartame.

    PubMed

    Ishii, H

    1981-03-01

    The brain tumorigenicity of aspartame (APM) and of its diketopiperazine (DKP) was studied in 860 SCL Wistar rats. APM at dietary levels of 1 g/kg, 2 gK/, 4 g/kg or APM + DKP (3:1) 4 g/kg was fed for 104 weeks. One atypical astrocytoma was found in a control rat and 2 astrocytomas, 2 oligodendrogliomas and 1 ependymoma were scattered among the 4 test groups. There was no significant difference in the incidence of brain tumors between control and test groups. It is concluded that neither AMP nor DKP caused brain tumors in rats in this study.

  11. Tumor-like lesions of the brain

    PubMed Central

    2009-01-01

    Abstract Differentiation between tumors and tumor-like lesions of the central nervous system is essential for planning adequate treatment and for estimating outcome and future prognosis. Neuroimaging fulfills an essential role in the correct differentiation between both entities. The radiologist should be aware of all non-neoplastic pathologies and diseases that may mimic tumors. High-end anatomic and functional neuroimaging tools integrating multiple modalities and clinical correlation is mandatory. In the current review, frequent tumor-like lesions are discussed. PMID:19965288

  12. An evaluative tool for preoperative planning of brain tumor resection

    NASA Astrophysics Data System (ADS)

    Coffey, Aaron M.; Garg, Ishita; Miga, Michael I.; Thompson, Reid C.

    2010-02-01

    A patient specific finite element biphasic brain model has been utilized to codify a surgeon's experience by establishing quantifiable biomechanical measures to score orientations for optimal planning of brain tumor resection. When faced with evaluating several potential approaches to tumor removal during preoperative planning, the goal of this work is to facilitate the surgeon's selection of a patient head orientation such that tumor presentation and resection is assisted via favorable brain shift conditions rather than trying to allay confounding ones. Displacement-based measures consisting of area classification of the brain surface shifting in the craniotomy region and lateral displacement of the tumor center relative to an approach vector defined by the surgeon were calculated over a range of orientations and used to form an objective function. The objective function was used in conjunction with Levenberg-Marquardt optimization to find the ideal patient orientation. For a frontal lobe tumor presentation the model predicts an ideal orientation that indicates the patient should be placed in a lateral decubitus position on the side contralateral to the tumor in order to minimize unfavorable brain shift.

  13. Optical detection of brain tumors using quantum dots

    NASA Astrophysics Data System (ADS)

    Toms, Steven A.; Daneshvar, Hamid; Muhammad, Osman; Jackson, Heather; Vogelbaum, Michael A.; Bruchez, Marcel

    2005-11-01

    Introduction: Brain tumor margin detection remains a challenging problem in the operative resection of gliomas. A novel nanoparticle, a PEGylated quantum dot, has been shown to be phagocytized by macrophages in vivo. This feature may allow quantum dots to co-localize with brain tumors and serve as an optical aid in the surgical resection of brain tumors. Methods: Sprague-Daly rats were injected intracranially with C6 gliosarcoma cell lines to establish tumors. Two weeks after implantation of brain tumors, PEGylated quantum dots emitting at 705 nm (PEG-705 QD) were injected via the tail vein. Twenty-four hours post PEG-705 QD injection, the animals were sacrificed and their tissues examined. Results: PEGylated quantum dots are avidly phagocytized by macrophages and are taken up by liver, spleen and lymph nodes. Macrophages and microglia co-localize with glioma cells, carrying the optical nanoparticle, the quantum dot. Excitation of the PEG-705 quantum dots gives off a deep red fluorescence detectable with charge coupled device (CCD) cameras, optical spectroscopy units, and in dark field fluorescence microscopy. Conclusions: PEG-705QDs co-localize with brain tumors and may serve as an optical adjunct to aid in the operative resection of gliomas. The particles may be visualized in surgery with CCD cameras or detected by optical spectroscopy.

  14. Possibilities of new therapeutic strategies in brain tumors.

    PubMed

    Bouffet, Eric; Tabori, Uri; Huang, Annie; Bartels, Ute

    2010-06-01

    Advances in the management of pediatric brain tumors have been less successful than in other areas of pediatric oncology. This gap in outcome is essentially related to specific aspects of these tumors in this age group such as the fact that the surrounding brain is still developing, vital structures limit aggressive attempts at removing infiltrating lesions, drug penetration into the central nervous system is often poor and short and long term toxicities of some treatments to the surrounding brain are significant. This review describes new therapeutic strategies and their impact in the pediatric neuro-oncology practice. Although the number of new active antineoplastic agents has been limited during the last decade, significant improvements in the chemotherapeutic management of pediatric brain tumors have been observed. These relate to the optimization of chemotherapy protocols, the development of new schedules of administration such as metronomic schedules, sequential high dose chemotherapy, concomitant administration of chemotherapy and radiation, or the introduction of intrathecal or intraventricular chemotherapy in specific protocols. Technological advances in radiotherapy allow delivering optimal doses to the target volume while decreasing the volume of normal surrounding tissue receiving radiation. As a consequence, conformal radiation therapy currently plays a major role in the management of several pediatric brain tumors, including in infants where radiation has been traditionally avoided. The role of molecularly targeted agents is still unclear and a number of phase I and II trials are ongoing to better define the future of these new therapies in pediatric brain tumors.

  15. 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.

  16. 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.

  17. Factors affecting intellectual outcome in pediatric brain tumor patients

    SciTech Connect

    Ellenberg, L.; McComb, J.G.; Siegel, S.E.; Stowe, S.

    1987-11-01

    A prospective study utilizing repeated intellectual testing was undertaken in 73 children with brain tumors consecutively admitted to Childrens Hospital of Los Angeles over a 3-year period to determine the effect of tumor location, extent of surgical resection, hydrocephalus, age of the child, radiation therapy, and chemotherapy on cognitive outcome. Forty-three patients were followed for at least two sequential intellectual assessments and provide the data for this study. Children with hemispheric tumors had the most general cognitive impairment. The degree of tumor resection, adequately treated hydrocephalus, and chemotherapy had no bearing on intellectual outcome. Age of the child affected outcome mainly as it related to radiation. Whole brain radiation therapy was associated with cognitive decline. This was especially true in children below 7 years of age, who experienced a very significant loss of function after whole brain radiation therapy.

  18. Neuromorphometry of primary brain tumors by magnetic resonance imaging.

    PubMed

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

    2015-04-01

    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 [Formula: see text], whereas oligodendrogliomas exhibit a mean of [Formula: see text]. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of [Formula: see text], and the necrotic region presented a mean of [Formula: see text]. 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

  19. 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

  20. Rho GTPases in primary brain tumor malignancy and invasion.

    PubMed

    Khalil, Bassem D; El-Sibai, Mirvat

    2012-07-01

    Gliomas are the most common type of malignant primary brain tumor in humans, accounting for 80 % of malignant cases. Expression and activity of Rho GTPases, which coordinate several cellular processes including cell-cycle progression and cell migration, are commonly altered in many types of primary brain tumor. Here we review the suggested effects of deregulated Rho GTPase signaling on brain tumor malignancy, highlighting the controversy in the field. For instance, whereas expression of RhoA and RhoB has been found to be significantly reduced in astrocytic tumors, other studies have reported Rho-dependent LPA-induced migration in glioma cells. Moreover, whereas the Rac1 expression level has been found to be reduced in astrocytic tumor, it was overexpressed and induced invasion in medulloblastoma tumors. In addition to the Rho GTPases themselves, several of their downstream effectors (including ROCK, mDia, and N-WASP) and upstream regulators (including GEFs, GAPs, PI3K, and PTEN) have also been implicated in primary brain tumors.

  1. Neuromorphometry of primary brain tumors by magnetic resonance imaging.

    PubMed

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

    2015-04-01

    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 [Formula: see text], whereas oligodendrogliomas exhibit a mean of [Formula: see text]. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of [Formula: see text], and the necrotic region presented a mean of [Formula: see text]. 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.

  2. Orthotopic models of pediatric brain tumors in zebrafish.

    PubMed

    Eden, C J; Ju, B; Murugesan, M; Phoenix, T N; Nimmervoll, B; Tong, Y; Ellison, D W; Finkelstein, D; Wright, K; Boulos, N; Dapper, J; Thiruvenkatam, R; Lessman, C A; Taylor, M R; Gilbertson, R J

    2015-03-26

    High-throughput screens (HTS) of compound toxicity against cancer cells can identify thousands of potential new drug-leads. But only limited numbers of these compounds can progress to expensive and labor-intensive efficacy studies in mice, creating a 'bottle neck' in the drug development pipeline. Approaches that triage drug-leads for further study are greatly needed. Here we provide an intermediary platform between HTS and mice by adapting mouse models of pediatric brain tumors to grow as orthotopic xenografts in the brains of zebrafish. Freshly isolated mouse ependymoma, glioma and choroid plexus carcinoma cells expressing red fluorescence protein were conditioned to grow at 34 °C. Conditioned tumor cells were then transplanted orthotopically into the brains of zebrafish acclimatized to ambient temperatures of 34 °C. Live in vivo fluorescence imaging identified robust, quantifiable and reproducible brain tumor growth as well as spinal metastasis in zebrafish. All tumor xenografts in zebrafish retained the histological characteristics of the corresponding parent mouse tumor and efficiently recruited fish endothelial cells to form a tumor vasculature. Finally, by treating zebrafish harboring ERBB2-driven gliomas with an appropriate cytotoxic chemotherapy (5-fluorouracil) or tyrosine kinase inhibitor (erlotinib), we show that these models can effectively assess drug efficacy. Our data demonstrate, for the first time, that mouse brain tumors can grow orthotopically in fish and serve as a platform to study drug efficacy. As large cohorts of brain tumor-bearing zebrafish can be generated rapidly and inexpensively, these models may serve as a powerful tool to triage drug-leads from HTS for formal efficacy testing in mice. PMID:24747973

  3. The therapy of infantile malignant brain tumors: current status?

    PubMed

    Kalifa, Chantal; Grill, Jacques

    2005-12-01

    Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood [1]. Genetic predisposition to infantile malignant brain tumors are known in Gorlin syndrome for example who present with desmoplastic medulloblastoma in about 5% of the affected patients. In addition, sequelae from tumor and its treatment are more severe at this age [2]. Thus, malignant brain tumors represent a true therapeutic challenge in neuro-oncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group. Since the end of the 80s, noninvasive imaging procedures produce accurate diagnosis of brain tumors and improvement in neurosurgery, neuroanesthesia and perioperative intensive care permit safe tumor resections or at least biopsies. Consequently, the pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications [3]. At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors [4]. Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors

  4. 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.

  5. 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

  6. Pediatric brain tumor treatment: growth consequences and their management.

    PubMed

    Mostoufi-Moab, Sogol; Grimberg, Adda

    2010-09-01

    Tumors of the central nervous system, the most common solid tumors of childhood, are a major source of cancer-related morbidity and mortality in children. Survival rates have improved significantly following treatment for childhood brain tumors, with this growing cohort of survivors at high risk of adverse medical and late effects. Endocrine morbidities are the most prominent disorder among the spectrum of longterm conditions, with growth hormone deficiency the most common endocrinopathy noted, either from tumor location or after cranial irradiation and treatment effects on the hypothalamic/pituitary unit. Deficiency of other anterior pituitary hormones can contribute to negative effects on growth, body image and composition, sexual function, skeletal health, and quality of life. Pediatric and adult endocrinologists often provide medical care to this increasing population. Therefore, a thorough understanding of the epidemiology and pathophysiology of growth failure as a consequence of childhood brain tumor, both during and after treatment, is necessary and the main focus of this review.

  7. 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

  8. 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.

  9. 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

  10. Primary brain tumors, delta 24 and tumor metabolism. Interview by Rona Williamson.

    PubMed

    Gilbert, Mark R

    2013-04-01

    Interview by Rona Williamson, Commissioning Editor Mark R Gilbert studied medicine at the Johns Hopkins School of Medicine in Baltimore (MD, USA). He completed residency training in internal medicine and neurology at the Johns Hopkins Hospital, then was named the first Keck Foundation Fellow in Neuro-Oncology at Johns Hopkins. After 2 years on the faculty at Johns Hopkins, he moved to the University of Pittsburgh to head the Brain Tumor Program. During his tenure at Pittsburgh (PA, USA), he was named Chair of the Brain Tumor Committee of the Eastern Cooperative Oncology Group. In 1996, Dr Gilbert moved to the Emory University in Atlanta (GA, USA) to lead the Medical Neuro-Oncology Program and successfully competed for the program's membership in the New Approaches to Brain Tumor Treatment consortium. Dr Gilbert moved to the MD Anderson Cancer Center in Houston (TX, USA) in 2000 as Deputy Chair of the Department of Neuro-Oncology. During his tenure at MD Anderson, he has created two brain tumor consortia. The Collaborative Ependymoma Research Network is an international effort that is focusing research efforts on patients, both adult and pediatric, with this uncommon central nervous system tumor. The Brain Tumor Trials Collaborative is a 23-institution consortium that focuses on innovative clinical trials for primary glial malignancies. In addition, Dr Gilbert holds a leadership position in the Radiation Therapy Oncology Group and has served as the principal investigator on several large randomized brain tumor clinical trials. His research focus has been in the area of clinical and translational research for primary brain tumors. This includes novel clinical trial designs and the integration of correlative tumor biology with these clinical studies.

  11. HFE polymorphisms affect survival of brain tumor patients.

    PubMed

    Lee, Sang Y; Slagle-Webb, Becky; Sheehan, Jonas M; Zhu, Junjia; Muscat, Joshua E; Glantz, Michael; Connor, James R

    2015-03-01

    The HFE (high iron) protein plays a key role in the regulation of body iron. HFE polymorphisms (H63D and C282Y) are the common genetic variants in Caucasians. Based on frequency data, both HFE polymorphisms have been associated with increased risk in a number of cancers. The prevalence of the two major HFE polymorphisms in a human brain tumor patient populations and the impact of HFE polymorphisms on survival have not been studied. In the present study, there is no overall difference in survival by HFE genotype. However, male GBM patients with H63D HFE (H63D) have poorer overall survival than wild type HFE (WT) male GBM (p = 0.03). In GBM patients with the C282Y HFE polymorphism (C282Y), female patients have poorer survival than male patients (p = 0.05). In addition, female metastatic brain tumor patients with C282Y have shorter survival times post diagnosis than WT patients (p = 0.02) or male metastatic brain tumor patients with C282Y (p = 0.02). There is a tendency toward a lower proportion of H63D genotype in GBM patients than a non-tumor control group (p = 0.09) or other subtypes of brain tumors. In conclusion, our study suggests that HFE genotype impacts survival of brain tumor patients in a gender specific manner. We previously reported that glioma and neuroblastoma cell lines with HFE polymorphisms show greater resistance to chemo and radiotherapy. Taken together, these data suggest HFE genotype is an important consideration for evaluating and planning therapeutic strategies in brain tumor patients.

  12. 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.

  13. Diagnosis and surgical treatment of childhood brain tumors.

    PubMed

    Wilson, C B

    1975-03-01

    As the most frequent solid tumor occurring in childhood, brain tumors constitute an important segment of pediatric oncology. Neurologic manifestations may be deceptively mild and easily overlooked or misinterpreted, particularly in the very young, because of the remarkable resiliency of the immature central nervous system and the skull's ability to expand throughout the pre-adolescent years. The majority of childhood tumors produce increased intracranial pressure, usually the consequence of obstructive hydrocephalus. Specific neurologic deficits correspond to the tumor's location. The posterior fossa harbors two-thirds of childhood tumors, and each of the four common tumors in this location produces a characteristic syndrome. Supratentorial tumors occupy the cerebral hemisphere, the suprasellar area, and the pineal gland. Diagnostic studies have reached a state of great sophistication and precise anatomical localization. Surgery, either alone or with adjuvant radiotherapy, cures no more than one-third of all tumors; for the remainder, it has a diagnostic and palliative role. The introduction of operative microsurgery has advanced the art, particularly in the surgical treatment of craniopharyngiomas and pinealomas, but any significant improvement in the treatment of brain tumors as a group seems unlikely to be achieved by surgery alone.

  14. 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

  15. Circulating biomarker panels for targeted therapy in brain tumors.

    PubMed

    Tanase, Cristiana; Albulescu, Radu; Codrici, Elena; Popescu, Ionela Daniela; Mihai, Simona; Enciu, Ana Maria; Cruceru, Maria Linda; Popa, Adrian Claudiu; Neagu, Ana Iulia; Necula, Laura Georgiana; Mambet, Cristina; Neagu, Monica

    2015-01-01

    An important goal of oncology is the development of cancer risk-identifier biomarkers that aid early detection and target therapy. High-throughput profiling represents a major concern for cancer research, including brain tumors. A promising approach for efficacious monitoring of disease progression and therapy could be circulating biomarker panels using molecular proteomic patterns. Tailoring treatment by targeting specific protein-protein interactions and signaling networks, microRNA and cancer stem cell signaling in accordance with tumor phenotype or patient clustering based on biomarker panels represents the future of personalized medicine for brain tumors. Gathering current data regarding biomarker candidates, we address the major challenges surrounding the biomarker field of this devastating tumor type, exploring potential perspectives for the development of more effective predictive biomarker panels.

  16. Novel Magnetic Resonance Imaging Techniques in Brain Tumors.

    PubMed

    Nechifor, Ruben E; Harris, Robert J; Ellingson, Benjamin M

    2015-06-01

    Magnetic resonance imaging is a powerful, noninvasive imaging technique with exquisite sensitivity to soft tissue composition. Magnetic resonance imaging is primary tool for brain tumor diagnosis, evaluation of drug response assessment, and clinical monitoring of the patient during the course of their disease. The flexibility of magnetic resonance imaging pulse sequence design allows for a variety of image contrasts to be acquired, including information about magnetic resonance-specific tissue characteristics, molecular dynamics, microstructural organization, vascular composition, and biochemical status. The current review highlights recent advancements and novel approaches in MR characterization of brain tumors.

  17. 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

  18. 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

  19. Dysphagia outcomes in patients with brain tumors undergoing inpatient rehabilitation.

    PubMed

    Wesling, Michele; Brady, Susan; Jensen, Mary; Nickell, Melissa; Statkus, Donna; Escobar, Nelson

    2003-01-01

    The purpose of this retrospective study was to compare functional dysphagia outcomes following inpatient rehabilitation for patients with brain tumors with that of patients following a stroke. Group 1 (n = 24) consisted of consecutive admissions to the brain injury program with the diagnosis of brain tumor and dysphagia. Group 2 (n = 24) consisted of matched, consecutive admissions, with the diagnosis of acute stroke and dysphagia. Group 2 was matched for age, site of lesion, and initial composite cognitive FIM score. The main outcome measures for this study included the American Speech-Language-Hearing Association (ASHA) National Outcome Measurement System (NOMS) swallowing scale, length of stay, hospital charges, and medical complications. Results showed that swallowing gains made by both groups as evaluated by the admission and discharge ASHA NOMS levels were considered to be statistically significant. The differences for length of stay, total hospital charges, and speech charges between the two groups were not considered to be statistically significant. Three patients in the brain tumor group (12.5%) demonstrated dysphagia complications of either dehydration or pneumonia during their treatment course as compared to 0% in the stroke group. This study confirms that functional dysphagia gains can be achieved for patients with brain tumors undergoing inpatient rehabilitation and that they should be afforded the same type and intensity of rehabilitation for their swallowing that is provided to patients following a stroke.

  20. Agnosias: recognition disorders in patients with brain tumors.

    PubMed

    Gainotti, Guido

    2012-06-01

    Two main varieties of recognition disorders are distinguished in neuropsychology: agnosias and semantic disorders. The term agnosias is generally used to denote recognition defects limited to a single perceptual modality (which is itself apparently intact), whereas the term semantic disorders is used to denote recognition defects involving all the sensory modalities in a roughly similar manner. Brain tumors can be one of the aetiologies underlying agnosias and semantic disorders. However, due to the heterogeneity and the rarity of recognition disorders, their investigation can be useful only to suggest or exclude the oncological nature of a brain lesion, but not to systematically monitor the clinical outcome in tumor patients. Furthermore, the relevance of recognition disorders as a hint toward a diagnosis of brain tumor varies according to the type of agnosia and of semantic disorder and the localization of the underlying brain pathology. The hypothesis that a variety of agnosia (or of semantic disorder) may be due to a neoplastic lesion can, therefore, be advanced if it is consistent with our knowledge about the usual localization and the growing patterns of different types of brain tumors.

  1. Tumor-infiltrating lymphocytes expressing IOT-10 marker. An immunohistochemical study of a series of 185 brain tumors.

    PubMed

    Zurita, M; Vaquero, J; Coca, S; Oya, S; Garcia, N

    1993-04-01

    The presence of IOT-10-positive lymphocytes among the tumor-infiltrating-lymphocyte (TIL) population was studied in a series of 185 brain tumors. In most of the tumors, IOT-10-positive lymphocytes were identified, but generally they were scarce and masked among the tumor cells, suggesting that NK-cells exercise a poor participation in the tissular response against brain tumors. Isolated tumor cells showing IOT-10-positivity were found in low-grade astrocytomas, neurinomas and medulloblastomas. IOT-10-positivity on both tumor neuropil and tumor cells was considered a characteristic finding in oligodendrogliomas. The number of IOT-10-positive NK-cells in brain metastases and in cerebellar hemangioblastomas was comparatively greater than in other types of brain tumor. Since in brain metastases, the presence of IOT-10-positive NK-cells can be related to the tissular response to an extracerebral malignancy, their considerable presence in cerebellar hemangioblastomas is an enigmatic finding that deserves further attention.

  2. 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

  3. A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies.

    PubMed

    Chadwick, Emily J; Yang, David P; Filbin, Mariella G; Mazzola, Emanuele; Sun, Yu; Behar, Oded; Pazyra-Murphy, Maria F; Goumnerova, Liliana; Ligon, Keith L; Stiles, Charles D; Segal, Rosalind A

    2015-11-07

    Brain tumors are a major cause of cancer-related morbidity and mortality. Developing new therapeutics for these cancers is difficult, as many of these tumors are not easily grown in standard culture conditions. Neurosphere cultures under serum-free conditions and orthotopic xenografts have expanded the range of tumors that can be maintained. However, many types of brain tumors remain difficult to propagate or study. This is particularly true for pediatric brain tumors such as pilocytic astrocytomas and medulloblastomas. This protocol describes a system that allows primary human brain tumors to be grown in culture. This quantitative assay can be used to investigate the effect of microenvironment on tumor growth, and to test new drug therapies. This protocol describes a system where fluorescently labeled brain tumor cells are grown on an organotypic brain slice from a juvenile mouse. The response of tumor cells to drug treatments can be studied in this assay, by analyzing changes in the number of cells on the slice over time. In addition, this system can address the nature of the microenvironment that normally fosters growth of brain tumors. This brain tumor organotypic slice co-culture assay provides a propitious system for testing new drugs on human tumor cells within a brain microenvironment.

  4. 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

  5. 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.

  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. 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.

  8. 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 ...

  9. 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…

  10. Life satisfaction in adult survivors of childhood brain tumors.

    PubMed

    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, lifelong 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 suggest 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 that 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.

  11. Gene Therapy for Brain Tumors: Basic Developments and Clinical Implementation

    PubMed Central

    Assi, Hikmat; Candolfi, Marianela; Baker, Gregory; Mineharu, Yohei; Lowenstein, Pedro R; Castro, Maria G

    2012-01-01

    Glioblastoma multiforme (GBM) is the most common and deadliest of adult primary brain tumors. Due to its invasive nature and sensitive location, complete resection remains virtually impossible. The resistance of GBM against chemotherapy and radiotherapy necessitate the development of novel therapies. Gene therapy is proposed for the treatment of brain tumors and has demonstrated pre-clinical efficacy in animal models. Here we review the various experimental therapies that have been developed for GBM including both cytotoxic and immune stimulatory approaches. We also review the combined conditional cytotoxic immune stimulatory therapy that our lab has developed which is dependent on the adenovirus mediated expression of the conditional cytotoxic gene, Herpes Simplex Type 1 Thymidine Kinase (TK) and the powerful DC growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Combined delivery of these vectors elicits tumor cell death and an anti-tumor adaptive immune response that requires TLR2 activation. The implications of our studies indicate that the combined cytotoxic and immunotherapeutic strategies are effective strategies to combat deadly brain tumors and warrant their implementation in human Phase I clinical trials for GBM. PMID:22906921

  12. Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers

    PubMed Central

    Zhang, Fan; Mastorakos, Panagiotis; Mishra, Manoj K.; Mangraviti, Antonella; Hwang, Lee; Zhou, Jinyuan; Hanes, Justin; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Kannan, Rangaramanujam M.

    2015-01-01

    Effective blood–brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (~6 mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma. PMID:25818456

  13. Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers.

    PubMed

    Zhang, Fan; Mastorakos, Panagiotis; Mishra, Manoj K; Mangraviti, Antonella; Hwang, Lee; Zhou, Jinyuan; Hanes, Justin; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Kannan, Rangaramanujam M

    2015-06-01

    Effective blood-brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (∼6 mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma.

  14. 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.

  15. 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.

  16. 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.

  17. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    PubMed Central

    Klinger, Neil V.

    2016-01-01

    Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors. PMID:27807473

  18. Clinical considerations for neutron capture therapy of brain tumors

    SciTech Connect

    Madoc-Jones, H.; Wazer, D.E.; Zamenhof, R.G.; Harling, O.K.; Bernard, J.A. Jr. )

    1990-01-01

    The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the United States in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should now be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam causes gamma rays to be generated when it interacts with tissue, we think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue. I look forward to the remainder of this Workshop, which will detail recent progress in the development of epithermal, as well as thermal, beams and new methods for tracking and measuring the uptake of boron in normal and tumor tissues. 10 references.

  19. Why does Jack, and not Jill, break his crown? Sex disparity in brain tumors

    PubMed Central

    2012-01-01

    It is often reported that brain tumors occur more frequently in males, and that males suffer a worse outcome from brain tumors than females. If correct, these observations suggest that sex plays a fundamental role in brain tumor biology. The following review of the literature regarding primary and metastatic brain tumors, reveals that brain tumors do occur more frequently in males compared to females regardless of age, tumor histology, or region of the world. Sexually dimorphic mechanisms that might control tumor cell biology, as well as immune and brain microenvironmental responses to cancer, are explored as the basis for this sex disparity. Elucidating the mechanisms by which sex chromosomes and sex hormones impact on brain tumorigenesis and progression will advance our understanding of basic cancer biology and is likely to be essential for optimizing the care of brain tumor patients. PMID:22277186

  20. Multiscale modeling for image analysis of brain tumor studies.

    PubMed

    Bauer, Stefan; May, Christian; Dionysiou, Dimitra; Stamatakos, Georgios; Büchler, Philippe; Reyes, Mauricio

    2012-01-01

    Image-based modeling of tumor growth combines methods from cancer simulation and medical imaging. In this context, we present a novel approach to adapt a healthy brain atlas to MR images of tumor patients. In order to establish correspondence between a healthy atlas and a pathologic patient image, tumor growth modeling in combination with registration algorithms is employed. In a first step, the tumor is grown in the atlas based on a new multiscale, multiphysics model including growth simulation from the cellular level up to the biomechanical level, accounting for cell proliferation and tissue deformations. Large-scale deformations are handled with an Eulerian approach for finite element computations, which can operate directly on the image voxel mesh. Subsequently, dense correspondence between the modified atlas and patient image is established using nonrigid registration. The method offers opportunities in atlas-based segmentation of tumor-bearing brain images as well as for improved patient-specific simulation and prognosis of tumor progression. PMID:21813362

  1. 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

  2. Mitochondrial control by DRP1 in brain tumor initiating cells.

    PubMed

    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

    2015-04-01

    Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells. 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 targeting AMPK rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca(2+)-calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTIC tumor cells, suggesting that tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlated with poor prognosis in glioblastoma, suggesting that mitochondrial dynamics may represent a therapeutic target for BTICs. PMID:25730670

  3. 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.

  4. 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.

  5. 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

  6. Emerging techniques and technologies in brain tumor imaging.

    PubMed

    Ellingson, Benjamin M; Bendszus, Martin; Sorensen, A Gregory; Pope, Whitney B

    2014-10-01

    The purpose of this report is to describe the state of imaging techniques and technologies for detecting response of brain tumors to treatment in the setting of multicenter clinical trials. Within currently used technologies, implementation of standardized image acquisition and the use of volumetric estimates and subtraction maps are likely to help to improve tumor visualization, delineation, and quantification. Upon further development, refinement, and standardization, imaging technologies such as diffusion and perfusion MRI and amino acid PET may contribute to the detection of tumor response to treatment, particularly in specific treatment settings. Over the next few years, new technologies such as 2(3)Na MRI and CEST imaging technologies will be explored for their use in expanding the ability to quantitatively image tumor response to therapies in a clinical trial setting.

  7. 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

    the brain tumor microenvironment, revealing novel aspects for adjuvant approaches and new clinical assessment criteria when applied to brain tumor patients. PMID:25458015

  8. 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.

  9. Pros and cons of current brain tumor imaging

    PubMed Central

    Ellingson, Benjamin M.; Wen, Patrick Y.; van den Bent, Martin J.; Cloughesy, Timothy F.

    2014-01-01

    Over the past 20 years, very few agents have been approved for the treatment of brain tumors. Recent studies have highlighted some of the challenges in assessing activity in novel agents for the treatment of brain tumors. This paper reviews some of the key challenges related to assessment of tumor response to therapy in adult high-grade gliomas and discusses the strengths and limitations of imaging-based endpoints. Although overall survival is considered the “gold standard” endpoint in the field of oncology, progression-free survival and response rate are endpoints that hold great value in neuro-oncology. Particular focus is given to advancements made since the January 2006 Brain Tumor Endpoints Workshop, including the development of Response Assessment in Neuro-Oncology criteria, the value of T2/fluid-attenuated inversion recovery, use of objective response rates and progression-free survival in clinical trials, and the evaluation of pseudoprogression, pseudoresponse, and inflammatory response in radiographic images. PMID:25313235

  10. 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

  11. Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

    PubMed

    Pietilä, Sari; Lenko, Hanna L; Oja, Sakari; Koivisto, Anna-Maija; Pietilä, Timo; Mäkipernaa, Anne

    2016-07-01

    This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment.

  12. Pediatric Brain Tumor Treatment: Growth Consequences and their Management

    PubMed Central

    Mostoufi-Moab, Sogol; Grimberg, Adda

    2014-01-01

    Tumors of the central nervous system, the most common solid tumors of childhood, are a major source of cancer-related morbidity and mortality in children. Survival rates have improved significantly following treatment for childhood brain tumors, with this growing cohort of survivors at high risk of adverse medical and late effects. Endocrine morbidities are the most prominent disorder among the spectrum of long-term conditions, with growth hormone deficiency the most common endocrinopathy noted, either from tumor location or after cranial irradiation and treatment effects on the hypothalamic/pituitary unit. Deficiency of other anterior pituitary hormones can contribute to negative effects on growth, body image and composition, sexual function, skeletal health, and quality of life. Pediatric and adult endocrinologists often provide medical care to this increasing population. Therefore, a thorough understanding of the epidemiology and pathophysiology of growth failure as a consequence of childhood brain tumor, both during and after treatment, is necessary and the main focus of this review. PMID:21037539

  13. 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

  14. Numerical simulations of MREIT conductivity imaging for brain tumor detection.

    PubMed

    Meng, Zi Jun; Sajib, Saurav Z K; Chauhan, Munish; Sadleir, Rosalind J; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2013-01-01

    Magnetic resonance electrical impedance tomography (MREIT) is a new modality capable of imaging the electrical properties of human body using MRI phase information in conjunction with external current injection. Recent in vivo animal and human MREIT studies have revealed unique conductivity contrasts related to different physiological and pathological conditions of tissues or organs. When performing in vivo brain imaging, small imaging currents must be injected so as not to stimulate peripheral nerves in the skin, while delivery of imaging currents to the brain is relatively small due to the skull's low conductivity. As a result, injected imaging currents may induce small phase signals and the overall low phase SNR in brain tissues. In this study, we present numerical simulation results of the use of head MREIT for brain tumor detection. We used a realistic three-dimensional head model to compute signal levels produced as a consequence of a predicted doubling of conductivity occurring within simulated tumorous brain tissues. We determined the feasibility of measuring these changes in a time acceptable to human subjects by adding realistic noise levels measured from a candidate 3 T system. We also reconstructed conductivity contrast images, showing that such conductivity differences can be both detected and imaged. PMID:23737862

  15. Numerical Simulations of MREIT Conductivity Imaging for Brain Tumor Detection

    PubMed Central

    Meng, Zi Jun; Sajib, Saurav Z. K.; Chauhan, Munish; Sadleir, Rosalind J.; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2013-01-01

    Magnetic resonance electrical impedance tomography (MREIT) is a new modality capable of imaging the electrical properties of human body using MRI phase information in conjunction with external current injection. Recent in vivo animal and human MREIT studies have revealed unique conductivity contrasts related to different physiological and pathological conditions of tissues or organs. When performing in vivo brain imaging, small imaging currents must be injected so as not to stimulate peripheral nerves in the skin, while delivery of imaging currents to the brain is relatively small due to the skull's low conductivity. As a result, injected imaging currents may induce small phase signals and the overall low phase SNR in brain tissues. In this study, we present numerical simulation results of the use of head MREIT for brain tumor detection. We used a realistic three-dimensional head model to compute signal levels produced as a consequence of a predicted doubling of conductivity occurring within simulated tumorous brain tissues. We determined the feasibility of measuring these changes in a time acceptable to human subjects by adding realistic noise levels measured from a candidate 3 T system. We also reconstructed conductivity contrast images, showing that such conductivity differences can be both detected and imaged. PMID:23737862

  16. 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

  17. Brain tumor segmentation in MRI based on fuzzy aggregators

    NASA Astrophysics Data System (ADS)

    Zhu, Yan; Liao, Qingmin; Dou, Weibei; Ruan, Su

    2005-07-01

    Magnetic Resonance Image (MRI) is widely used in radiology diagnosis, especially in pathology detection in human brain. Most of the methods now applied to automatically segment brain tumors rely on T1-weighted sequences exclusively despite the fact that the imaging agent is multi-spectral. The work focuses on the integration or fusion of information provided by each sequence, i.e. T1, T2 and PD. Based on the fuzzy aggregators proposed in fuzzy theory, a system integrating all these information is established. The paper discusses some famous operators, their properties and application in tumor segmentation. In particular, Davies-Bouldin index is used to determine the parameters of the parametric operations. The result shows the importance of data fusion in segmentation process, discovers that T-norms are less robust to noise compared with mean operators. Meanwhile, weights allocated illustrate the order of importance of each spectrum in pathology detection, and are in agreement with their characteristic.

  18. Use of chlorotoxin for targeting of primary brain tumors.

    PubMed

    Soroceanu, L; Gillespie, Y; Khazaeli, M B; Sontheimer, H

    1998-11-01

    Gliomas are primary brain tumors that arise from differentiated glial cells through a poorly understood malignant transformation. Although glioma cells retain some genetic and antigenic features common to glial cells, they show a remarkable degree of antigenic heterogeneity and variable mutations in their genome. Glioma cells have recently been shown to express a glioma-specific chloride ion channel (GCC) that is sensitive to chlorotoxin (CTX), a small peptide purified from Leiurus quinquestriatus scorpion venom [N. Ullrich et al, Neuroreport, 7: 1020-1024, 1996; and N. Ullrich and H. Sontheimer, Am. J. Physiol. (Cell Physiol.), 270: C1511-C1521, 1996]. Using native and recombinant 125I-labeled CTX, we show that toxin binding to glioma cells is specific and involves high affinity [dissociation constant (Kd)=4.2 nM] and low affinity (Kd=660 nml) binding sites. In radioreceptor assays, 125I-labeled CTX binds to a protein with Mr=72,000, presumably GCC or a receptor that modulates GCC activity. In vivo targeting and biodistribution experiments were obtained using 125I- and (131)I-labeled CTX injected into severe combined immunodeficient mice bearing xenografted gliomas. CTX selectively accumulated in the brain of tumor-bearing mice with calculated brain: muscle ratios of 36.4% of injected dose/g (ID/g), as compared to 12.4% ID/g in control animals. In the tumor-bearing severe combined immunodeficient mice, the vast majority of the brain-associated radioactivity was localized within the tumor (tumor:muscle ratio, 39.13% ID/g; contralateral brain:muscle ratio, 6.68%ID/g). Moreover, (131)I-labeled CTX distribution, visualized through in vivo imaging by gamma ray camera scans, demonstrates specific and persistent intratumoral localization of the radioactive ligand. Immunohistochemical studies using biotinylated and fluorescently tagged CTX show highly selective staining of glioma cells in vitro, in situ, and in sections of patient biopsies. Comparison tissues including

  19. Drosophila neural stem cells in brain development and tumor formation.

    PubMed

    Jiang, Yanrui; Reichert, Heinrich

    2014-01-01

    Neuroblasts, the neural stem cells in Drosophila, generate the complex neural structure of the central nervous system. Significant progress has been made in understanding the mechanisms regulating the self-renewal, proliferation, and differentiation in Drosophila neuroblast lineages. Deregulation of these mechanisms can lead to severe developmental defects and the formation of malignant brain tumors. Here, the authors review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system.

  20. Liposomally formulated phospholipid-conjugated indocyanine green for intra-operative brain tumor detection and resection.

    PubMed

    Suganami, Akiko; Iwadate, Yasuo; Shibata, Sayaka; Yamashita, Masamichi; Tanaka, Tsutomu; Shinozaki, Natsuki; Aoki, Ichio; Saeki, Naokatsu; Shirasawa, Hiroshi; Okamoto, Yoshiharu; Tamura, Yutaka

    2015-12-30

    Some tumor-specific near-infrared (NIR) fluorescent dyes such as indocyanine green (ICG), IDRye800CW, and 5-aminolevulinic acid have been used clinically for detecting tumor margins or micro-cancer lesions. In this study, we evaluated the physicochemical properties of liposomally formulated phospholipid-conjugated ICG, denoted by LP-iDOPE, as a clinically translatable NIR imaging nanoparticle for brain tumors. We also confirmed its brain-tumor-specific biodistribution and its characteristics as the intra-operative NIR imaging nanoparticles for brain tumor surgery. These properties of LP-iDOPE may enable neurosurgeons to achieve more accurate identification and more complete resection of brain tumor.

  1. 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

  2. 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.

  3. The p53 gene and protein in human brain tumors

    SciTech Connect

    Louis, D.N. )

    1994-01-01

    Because p53 gene alterations are commonplace in human tumors and because p53 protein is involved in a number of important cellular pathways, p53 has become a topic of intensive investigation, both by basic scientists and clinicians. p53 was initially identified by two independent laboratories in 1979 as a 53 kilodalton (kD) protein that complexes with the large T antigen of SV40 virus. Shortly thereafter, it was shown that the E1B oncoprotein of adenovirus also binds p53. The binding of two different oncogenic viral tumor proteins to the same cellular protein suggested that p53 might be integral to tumorigenesis. The human p53 cDNA and gene were subsequently cloned in the mid-1980s, and analysis of p53 gene alterations in human tumors followed a few year later. During these 10 years, researchers grappling with the vagaries of p53 first characterized the gene as an oncogene, then as a tumor suppressor gene, and most recently as both a tumor suppressor gene and a so-called [open quotes]dominant negative[close quotes] oncogene. The last few years have seen an explosion in work on this single gene and its protein product. A review of a computerized medical database revealed approximately 650 articles on p53 in 1992 alone. p53 has assumed importance in neuro-oncology because p53 mutations and protein alterations are frequent in the common diffuse, fibrillary astrocytic tumors of adults. p53 mutations in astrocytomas were first described in 1989 and were followed by more extensive analyses of gene mutations and protein alterations in adult astrocytomas. The gene has also been studied in less common brain tumors. Elucidating the role of p53 in brain tumorigenesis will not only enhance understanding of brain tumor biology but may also contribute to improved diagnosis and therapy. This discussion reviews key aspects of the p53 gene and protein, and describe their emerging roles in central nervous system neoplasia. 102 refs., 6 figs., 1 tab.

  4. Prospective study of neuropsychological sequelae in children with brain tumors

    SciTech Connect

    Bordeaux, J.D.; Dowell, R.E. Jr.; Copeland, D.R.; Fletcher, J.M.; Francis, D.J.; van Eys, J.

    1988-01-01

    Surgery and radiotherapy are the primary modalities of treatment for pediatric brain tumors. Despite the widespread use of these treatments, little is known of their acute effects (within one year posttreatment) on neuropsychological functions. An understanding of acute treatment effects may provide valuable feedback to neurosurgeons and a baseline against which delayed sequelae may be evaluated. This study compares pre- and posttherapy neuropsychological test performance of pediatric brain tumor patients categorized into two groups on the basis of treatment modalities: surgery (n = 7) and radiotherapy (n = 7). Treatment groups were composed of children aged 56 to 196 months at the time of evaluation with heterogeneous tumor diagnoses and locations. Comparisons of pretherapy findings with normative values using confidence intervals indicated that both groups performed within the average range on most measures. Outstanding deficits at baseline were observed on tests of fine-motor, psychomotor, and timed language skills, and are likely to be attributable to tumor-related effects. Comparisons of pre- versus posttherapy neuropsychological test findings indicated no significant interval changes for either group. Results suggest that surgery and radiotherapy are not associated with acute effects on neuropsychological functions.

  5. Radiosurgery in the management of pediatric brain tumors.

    PubMed

    Raco, A; Raimondi, A J; D'Alonzo, A; Esposito, V; Valentino, V

    2000-05-01

    A total of 114 patients with benign and malignant intracranial tumors were treated by Valentino at the Flaminia Radiosurgical Center using a Philips 6-MeV linear accelerator between 1987 and 1995. The tumor locations break down as follows: 36 in the cerebral hemispheres, 14 in the region of the hypothalamus/optic chiasm, 21 in the III ventricle/pineal region, 3 in the basal ganglia, 27 in the posterior fossa, 13 in the brain stem. Seventy-nine patients had multivariate/combined treatment consisting of surgery or biopsy followed by chemotherapy, radiotherapy and/or radiosurgery. Thirty-five were not operated on or biopsied but were treated primarily by radiosurgery, which was associated with chemotherapy and conventional radiotherapy. The short- and long-term results were evaluated separately for each pathology in an attempt to derive guidelines for future treatment. For tumors of the pineal region, we are of the opinion that radiosurgery is the treatment of choice in children and that more than one-third of patients can be cured by this means. The remaining patients require surgery and/or chemotherapy in addition. For medulloblastomas radiosurgery may be useful to control local recurrence if coupled with chemotherapy. In the case of ependymomas, partly because of the extreme malignancy of the lesions in our series, radiosurgery did not succeed in controlling local recurrence. We fear that limiting treatment to radiosurgery, rather than prescribing conventional radiotherapy when indicated, could permit CNS seeding. For craniopharyngiomas radiosurgery proved useful for controlling solid remnants. In glial tumors radiosurgery helped either to "sterilize" the tumor bed after removal or to treat remnants of the lesions in critical areas; for diffuse brain stem gliomas it should be considered the treatment of choice.

  6. Image updating for brain deformation compensation in tumor resection

    NASA Astrophysics Data System (ADS)

    Fan, Xiaoyao; Ji, Songbai; Olson, Jonathan D.; Roberts, David W.; Hartov, Alex; Paulsen, Keith D.

    2016-03-01

    Preoperative magnetic resonance images (pMR) are typically used for intraoperative guidance in image-guided neurosurgery, the accuracy of which can be significantly compromised by brain deformation. Biomechanical finite element models (FEM) have been developed to estimate whole-brain deformation and produce model-updated MR (uMR) that compensates for brain deformation at different surgical stages. Early stages of surgery, such as after craniotomy and after dural opening, have been well studied, whereas later stages after tumor resection begins remain challenging. In this paper, we present a method to simulate tumor resection by incorporating data from intraoperative stereovision (iSV). The amount of tissue resection was estimated from iSV using a "trial-and-error" approach, and the cortical shift was measured from iSV through a surface registration method using projected images and an optical flow (OF) motion tracking algorithm. The measured displacements were employed to drive the biomechanical brain deformation model, and the estimated whole-brain deformation was subsequently used to deform pMR and produce uMR. We illustrate the method using one patient example. The results show that the uMR aligned well with iSV and the overall misfit between model estimates and measured displacements was 1.46 mm. The overall computational time was ~5 min, including iSV image acquisition after resection, surface registration, modeling, and image warping, with minimal interruption to the surgical flow. Furthermore, we compare uMR against intraoperative MR (iMR) that was acquired following iSV acquisition.

  7. Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy

    PubMed Central

    Wankhede, Mamta; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Costas G

    2012-01-01

    Magnetic nanoparticles (MNPs) represent a promising nanomaterial for the targeted therapy and imaging of malignant brain tumors. Conjugation of peptides or antibodies to the surface of MNPs allows direct targeting of the tumor cell surface and potential disruption of active signaling pathways present in tumor cells. Delivery of nanoparticles to malignant brain tumors represents a formidable challenge due to the presence of the blood–brain barrier and infiltrating cancer cells in the normal brain. Newer strategies permit better delivery of MNPs systemically and by direct convection-enhanced delivery to the brain. Completion of a human clinical trial involving direct injection of MNPs into recurrent malignant brain tumors for thermotherapy has established their feasibility, safety and efficacy in patients. Future translational studies are in progress to understand the promising impact of MNPs in the treatment of malignant brain tumors. PMID:22390560

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Adaptive Intuitionistic Fuzzy Enhancement of Brain Tumor MR Images

    PubMed Central

    Deng, He; Deng, Wankai; Sun, Xianping; Ye, Chaohui; Zhou, Xin

    2016-01-01

    Image enhancement techniques are able to improve the contrast and visual quality of magnetic resonance (MR) images. However, conventional methods cannot make up some deficiencies encountered by respective brain tumor MR imaging modes. In this paper, we propose an adaptive intuitionistic fuzzy sets-based scheme, called as AIFE, which takes information provided from different MR acquisitions and tries to enhance the normal and abnormal structural regions of the brain while displaying the enhanced results as a single image. The AIFE scheme firstly separates an input image into several sub images, then divides each sub image into object and background areas. After that, different novel fuzzification, hyperbolization and defuzzification operations are implemented on each object/background area, and finally an enhanced result is achieved via nonlinear fusion operators. The fuzzy implementations can be processed in parallel. Real data experiments demonstrate that the AIFE scheme is not only effectively useful to have information from images acquired with different MR sequences fused in a single image, but also has better enhancement performance when compared to conventional baseline algorithms. This indicates that the proposed AIFE scheme has potential for improving the detection and diagnosis of brain tumors. PMID:27786240

  13. 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

  14. 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

  15. 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.

  16. Spatial organization and correlations of cell nuclei in brain tumors.

    PubMed

    Jiao, Yang; Berman, Hal; Kiehl, Tim-Rasmus; Torquato, Salvatore

    2011-01-01

    Accepting the hypothesis that cancers are self-organizing, opportunistic systems, it is crucial to understand the collective behavior of cancer cells in their tumorous heterogeneous environment. In the present paper, we ask the following basic question: Is this self-organization of tumor evolution reflected in the manner in which malignant cells are spatially distributed in their heterogeneous environment? We employ a variety of nontrivial statistical microstructural descriptors that arise in the theory of heterogeneous media to characterize the spatial distributions of the nuclei of both benign brain white matter cells and brain glioma cells as obtained from histological images. These descriptors, which include the pair correlation function, structure factor and various nearest neighbor functions, quantify how pairs of cell nuclei are correlated in space in various ways. We map the centroids of the cell nuclei into point distributions to show that while commonly used local spatial statistics (e.g., cell areas and number of neighboring cells) cannot clearly distinguish spatial correlations in distributions of normal and abnormal cell nuclei, their salient structural features are captured very well by the aforementioned microstructural descriptors. We show that the tumorous cells pack more densely than normal cells and exhibit stronger effective repulsions between any pair of cells. Moreover, we demonstrate that brain gliomas are organized in a collective way rather than randomly on intermediate and large length scales. The existence of nontrivial spatial correlations between the abnormal cells strongly supports the view that cancer is not an unorganized collection of malignant cells but rather a complex emergent integrated system.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

    PubMed Central

    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 António; 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

    2016-01-01

    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

  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. 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.

  4. 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.

  5. Tumor treating fields: a novel treatment modality and its use in brain tumors.

    PubMed

    Hottinger, Andreas F; Pacheco, Patricia; Stupp, Roger

    2016-10-01

    Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200kHz), which have been demonstrated to block cell division and interfere with organelle assembly. This novel treatment modality has shown promise in a variety of tumor types. It has been evaluated in randomized phase 3 trials in glioblastoma (GBM) and demonstrated to prolong progression-free survival (PFS) and overall survival (OS) when administered together with standard maintenance temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM. TTFields are continuously delivered by 4 transducer arrays consisting each of 9 insulated electrodes that are placed on the patient's shaved scalp and connected to a portable device. Here we summarize the preclinical data and mechanism of action, the available clinical data, and further outlook of this treatment modality in brain tumors and other cancer indications. PMID:27664860

  6. Tumor treating fields: a novel treatment modality and its use in brain tumors

    PubMed Central

    Pacheco, Patricia

    2016-01-01

    Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200kHz), which have been demonstrated to block cell division and interfere with organelle assembly. This novel treatment modality has shown promise in a variety of tumor types. It has been evaluated in randomized phase 3 trials in glioblastoma (GBM) and demonstrated to prolong progression-free survival (PFS) and overall survival (OS) when administered together with standard maintenance temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM. TTFields are continuously delivered by 4 transducer arrays consisting each of 9 insulated electrodes that are placed on the patient’s shaved scalp and connected to a portable device. Here we summarize the preclinical data and mechanism of action, the available clinical data, and further outlook of this treatment modality in brain tumors and other cancer indications. PMID:27664860

  7. 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.

  8. 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.

  9. Bystander effect-mediated therapy of experimental brain tumor by genetically engineered tumor cells.

    PubMed

    Namba, H; Tagawa, M; Iwadate, Y; Kimura, M; Sueyoshi, K; Sakiyama, S

    1998-01-01

    Transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene, followed by administration of ganciclovir (GCV), generates the "bystander effect," in which HSV-tk-negative wild-type cells, as well as HSV-tk-expressing cells, are killed by GCV. To eradicate an intracranial tumor by this bystander effect, we injected the tumor cells transduced with the HSV-tk gene (TK cells) in the vicinity of the preimplanted wild-type tumor and then administered GCV. Wild-type 9L-gliosarcoma cells (1 x 10[5]) were implanted into the brain of syngeneic Fisher rats. On the next day, rats were injected with TK cells (1 x 10(5) or 3 x 10[5]) or medium alone at the same brain coordinate and then treated with GCV or saline. Administration of GCV significantly prolonged the survival of the rats injected with TK cells compared with that injected with medium alone (p < 0.01). Reduction in tumor size and retardation of tumor growth were observed by serial magnetic resonance imaging in the rats that received the combination of TK cells and GCV. The results show that the bystander effect is also achieved in vivo even when TK cells and wild-type cells are not simultaneously implanted. This treatment modality circumvents potential risks accompanied with in vivo gene transfer. Because there remained substantially no HSV-tk-positive cells in the recurrent tumors, this modality offers a "safe" therapeutic strategy against human malignant gliomas. PMID:9458237

  10. 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

  11. Blood-tissue barrier of human brain tumors: correlation of scintigraphic and ultrastructural finding: concise communication

    SciTech Connect

    Front, D.; Israel, O.; Kohn, S.; Nir, I.

    1984-04-01

    Through the first 2 hr, uptake of (Tc-99m)pertechnetate and of Co-57 bleomycin were assessed in 29 brain tumors and were correlated with the ultrastructure of the tumor's capillary endothelium. No difference in uptake was found between the two tracers. Permeability of brain tumors to these agents was found to be governed by the same ultrastructural features that determine permeability in experimental brain tumors: the type of junction between contiguous endothelial cells in the capillaries. That uptake of (Tc-99m)pertechnetate and of Co-57 bleomycin depends on tumor capillary ultrastructure (which determines the permeability) suggests the possibility of the use of radiopharmaceuticals as in vivo indicators of tumor permeability. Brain scintigraphy may help to assess brain-tumor availability to non-lipid-soluble chemotherapeutic drugs.

  12. 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.

  13. 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

  14. Consensus Conference on Brain Tumor Definition for registration. November 10, 2000.

    PubMed Central

    McCarthy, Bridget J.; Surawicz, Tanya; Bruner, Janet M.; Kruchko, Carol; Davis, Faith

    2002-01-01

    The Consensus Conference on Brain Tumor Definition was facilitated by the Central Brain Tumor Registry of the United States and held on November 10, 2000, in Chicago, Illinois, to reach multidisciplinary agreement on a standard definition of brain tumors for collecting and comparing data in the U.S. The Brain Tumor Working Group, convened in 1998 to determine the status of brain tumor collection in the U.S., outlined 4 recommendations of which the first 2 guided the discussion for the Consensus Conference: (1) standardization of a definition of primary brain tumors that is based on site alone, rather than on site and behavior, and that can be used by surveillance organizations in collecting these tumors; and (2) development of a reporting scheme that can be used for comparing estimates of primary brain tumors across registries. Consensus was reached on the collection of all primary brain tumor histologies found and reported in the brain or CNS ICD-O site codes (C70.0-C72.9 and C75.1-C75.3), including those coded benign and uncertain as well as those coded malignant. In addition, a comprehensive listing of histologies occurring in the brain and CNS, based on the CBTRUS grouping scheme, was formulated to provide a template for reporting in accordance with the second recommendation of the Brain Tumor Working Group. With consensus achieved on the first 2 recommendations, the stage is set to move forward in estimating additional resources necessary for the collection of these tumors, including funding, training for cancer registrars, identifying quality control measures, and developing computerized edit checks, as outlined in the last 2 recommendations of the Brain Tumor Working Group. PMID:11916506

  15. 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 ...

  16. 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

  17. Gene Therapy and Virotherapy: Novel Therapeutic Approaches for Brain Tumors

    PubMed Central

    Kroeger, Kurt M.; Ghulam Muhammad, A.K.M.; Baker, Gregory J.; Assi, Hikmat; Wibowo, Mia K.; Xiong, Weidong; Yagiz, Kader; Candolfi, Marianela; Lowenstein, Pedro R.; Castro, Maria G.

    2010-01-01

    Glioblastoma multiforme (GBM) is a deadly primary brain tumor in adults, with a median survival of ~12–18 months post-diagnosis. Despite recent advances in conventional therapeutic approaches, only modest improvements in median survival have been achieved; GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are desperately needed. Our group and others are pursuing virotherapy and gene therapy strategies for the treatment of GBM. In this review, we will discuss various virotherapy and gene therapy approaches for GBM currently under preclinical and clinical evaluation including direct or conditional cytotoxic, and/or immunostimulatory approaches. We also discuss cutting-edge technologies for drug/gene delivery and targeting brain tumors, including the use of stem cells as delivery platforms, the use of targeted immunotoxins, and the therapeutic potential of using GBM microvesicles to deliver therapeutic siRNAs or virotherapies. Finally, various animal models available to test novel GBM therapies are discussed. PMID:21034670

  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. 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

  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. 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.

  2. 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

  3. Brain Magnetic Resonance Imaging After High-Dose Chemotherapy and Radiotherapy for Childhood Brain Tumors

    SciTech Connect

    Spreafico, Filippo Gandola, Lorenza; Marchiano, Alfonso; Simonetti, Fabio; Poggi, Geraldina; Adduci, Anna; Clerici, Carlo Alfredo; Luksch, Roberto; Biassoni, Veronica; Meazza, Cristina; Catania, Serena; Terenziani, Monica; Musumeci, Renato; Fossati-Bellani, Franca; Massimino, Maura

    2008-03-15

    Purpose: Brain necrosis or other subacute iatrogenic reactions has been recognized as a potential complication of radiotherapy (RT), although the possible synergistic effects of high-dose chemotherapy and RT might have been underestimated. Methods and Materials: We reviewed the clinical and radiologic data of 49 consecutive children with malignant brain tumors treated with high-dose thiotepa and autologous hematopoietic stem cell rescue, preceded or followed by RT. The patients were assessed for neurocognitive tests to identify any correlation with magnetic resonance imaging (MRI) anomalies. Results: Of the 49 children, 18 (6 of 25 with high-grade gliomas and 12 of 24 with primitive neuroectodermal tumors) had abnormal brain MRI findings occurring a median of 8 months (range, 2-39 months) after RT and beginning to regress a median of 13 months (range, 2-26 months) after onset. The most common lesion pattern involved multiple pseudonodular, millimeter-size, T{sub 1}-weighted unevenly enhancing, and T{sub 2}-weighted hyperintense foci. Four patients with primitive neuroectodermal tumors also had subdural fluid leaks, with meningeal enhancement over the effusion. One-half of the patients had symptoms relating to the new radiographic findings. The MRI lesion-free survival rate was 74% {+-} 6% at 1 year and 57% {+-} 8% at 2 years. The number of marrow ablative courses correlated significantly to the incidence of radiographic anomalies. No significant difference was found in intelligent quotient scores between children with and without radiographic changes. Conclusion: Multiple enhancing cerebral lesions were frequently seen on MRI scans soon after high-dose chemotherapy and RT. Such findings pose a major diagnostic challenge in terms of their differential diagnosis vis-a-vis recurrent tumor. Their correlation with neurocognitive results deserves further investigation.

  4. The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor.

    PubMed Central

    Criscuolo, G. R.

    1993-01-01

    Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors. They contribute to the mass effect imposed by the primary tumor and are often responsible for a patient's signs and symptoms. Cerebral edema significantly increases the morbidity associated with tumor biopsy, excision, radiation therapy, and chemotherapy. Both edema and cyst formation are thought to result from a deficiency in the blood-brain barrier, with consequent extravasation of water, electrolytes, and plasma proteins from altered tumor microvessels. The resultant expansion of the cerebral interstitial space contributes to the elevated intracranial pressure observed with brain tumors. Departure from the typical blood-brain barrier microvascular architecture may only partially explain the occurrence of edema and tumor cyst formation. Biochemical mediators have also been implicated in vascular extravasation. Vascular permeability factor or vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been isolated from a variety of tumors including human brain tumors. VPFb is an extraordinarily potent inducer of both microvascular extravasation (edemagenesis) and the formation of new blood vessels (angiogenesis). Its role in tumor growth and progression would therefore appear pivotal. Herein, the author presents an updated account of the investigation of VPF. Historical and clinical perspectives of the study and treatment of tumor associated edema are provided. The efficacy of high-dose dexamethasone in the treatment of neoplastic brain edema is discussed. A hypothetical role for VPF in edemagenesis is presented and discussed. It is hoped that an expanded understanding of the mechanisms responsible for the genesis of edema will ultimately facilitate therapeutic intervention. Images Figure 1 Figure 2 Figure 3 PMID:7516104

  5. Significant predictors of patients' uncertainty in primary brain tumors.

    PubMed

    Lin, Lin; Chien, Lung-Chang; Acquaye, Alvina A; Vera-Bolanos, Elizabeth; Gilbert, Mark R; Armstrong, Terri S

    2015-05-01

    Patients with primary brain tumors (PBT) face uncertainty related to prognosis, symptoms and treatment response and toxicity. Uncertainty is correlated to negative mood states and symptom severity and interference. This study identified predictors of uncertainty during different treatment stages (newly-diagnosed, on treatment, followed-up without active treatment). One hundred eighty six patients with PBT were accrued at various points in the illness trajectory. Data collection tools included: a clinical checklist/a demographic data sheet/the Mishel Uncertainty in Illness Scale-Brain Tumor Form. The structured additive regression model was used to identify significant demographic and clinical predictors of illness-related uncertainty. Participants were primarily white (80 %) males (53 %). They ranged in age from 19-80 (mean = 44.2 ± 12.6). Thirty-two of the 186 patients were newly-diagnosed, 64 were on treatment at the time of clinical visit with MRI evaluation, 21 were without MRI, and 69 were not on active treatment. Three subscales (ambiguity/inconsistency; unpredictability-disease prognoses; unpredictability-symptoms and other triggers) were different amongst the treatment groups (P < .01). However, patients' uncertainty during active treatment was as high as in newly-diagnosed period. Other than treatment stages, change of employment status due to the illness was the most significant predictor of illness-related uncertainty. The illness trajectory of PBT remains ambiguous, complex, and unpredictable, leading to a high incidence of uncertainty. There was variation in the subscales of uncertainty depending on treatment status. Although patients who are newly diagnosed reported the highest scores on most of the subscales, patients on treatment felt more uncertain about unpredictability of symptoms than other groups. Due to the complexity and impact of the disease, associated symptoms, and interference with functional status, comprehensive assessment of patients

  6. Cognitive dysfunction in children with brain tumors at diagnosis

    PubMed Central

    Studer, Martina; Ritter, Barbara Catherine; Steinlin, Maja; Leibundgut, Kurt; Heinks, Theda

    2015-01-01

    Background Survivors of brain tumors have a high risk for a wide range of cognitive problems. These dysfunctions are caused by the lesion itself and its surgical removal, as well as subsequent treatments (chemo‐ and/or radiation therapy). Multiple recent studies have indicated that children with brain tumors (BT) might already exhibit cognitive problems at diagnosis, i.e., before the start of any medical treatment. The aim of the present study was to investigate the baseline neuropsychological profile in children with BT compared to children with an oncological diagnosis not involving the central nervous system (CNS). Methods Twenty children with BT and 27 children with an oncological disease without involvement of the CNS (age range: 6.1–16.9 years) were evaluated with an extensive battery of neuropsychological tests tailored to the patient's age. Furthermore, the child and his/her parent(s) completed self‐report questionnaires about emotional functioning and quality of life. In both groups, tests were administered before any therapeutic intervention such as surgery, chemotherapy, or irradiation. Groups were comparable with regard to age, gender, and socioeconomic status. Results Compared to the control group, patients with BTs performed significantly worse in tests of working memory, verbal memory, and attention (effect sizes between 0.28 and 0.47). In contrast, the areas of perceptual reasoning, processing speed, and verbal comprehension were preserved at the time of measurement. Conclusion Our results highlight the need for cognitive interventions early in the treatment process in order to minimize or prevent academic difficulties as patients return to school. Pediatr Blood Cancer 2015;62:1805–1812. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc. PMID:26053691

  7. Household pesticides and risk of pediatric brain tumors.

    PubMed Central

    Pogoda, J M; Preston-Martin, S

    1997-01-01

    A follow-up to a population-based case-control study of pediatric brain tumors in Los Angeles County, California, involving mothers of 224 cases and 218 controls, investigated the risk of household pesticide use from pregnancy to diagnosis. Risk was significantly elevated for prenatal exposure to flea/tick pesticides -odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.1-2.6-, particularly among subjects less than 5 years old at diagnosis (OR = 2.5; CI, 1. 2-5.5). Prenatal risk was highest for mothers who prepared, applied, or cleaned up flea/tick products themselves (OR = 2.2; CI, 1.1-4.2; for subjects <5 years of age, OR = 5.4; CI, 1.3-22.3). A significant trend of increased risk with increased exposure was observed for number of pets treated (p = 0.04). Multivariate analysis of types of flea/tick products indicated that sprays/foggers were the only products significantly related to risk (OR =10.8; CI, 1.3-89.1). Elevated risks were not observed for termite or lice treatments, pesticides for nuisance pests, or yard and garden insecticides, herbicides, fungicides, or snail killer. Certain precautions,if ignored, were associated with significant increased risk: evacuating the house after spraying or dusting for pests (OR = 1.6; CI, 1.0-2.6), delaying the harvest of food after pesticide treatment (OR = 3.6; CI, 1.0-13.7), and following instructions on pesticide labels (OR = 3. 7;CI, 1.5-9.6). These findings indicate that chemicals used in flea/tick products may increase risk of pediatric brain tumors and suggest that further research be done to pinpoint specific chemicals involved. PMID:9370522

  8. Drug-Resistant Brain Metastases: A Role for Pharmacology, Tumor Evolution, and Too-Late Therapy.

    PubMed

    Stricker, Thomas; Arteaga, Carlos L

    2015-11-01

    Two recent studies report deep molecular profiling of matched brain metastases and primary tumors. In both studies, somatic alterations in the brain metastases were frequently discordant with those in the primary tumor, suggesting divergent evolution at metastatic sites and raising questions about the use of biomarkers in patients in clinical trials with targeted therapies.

  9. 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

    2011-03-01

    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. In the first set of experiments, cell migration away from a tumor spheroid was investigated. The second set of experiments was performed in a typical wound-healing geometry: Cells were placed on a substrate, a scratch was made, and cell migration into the gap was investigated. Experiments show a surprising result: 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.

  10. Donepezil in Treating Young Patients With Primary Brain Tumors Previously Treated With Radiation Therapy to the Brain

    ClinicalTrials.gov

    2016-07-26

    Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Children; Neurotoxicity; Psychosocial Effects of Cancer and Its Treatment; Radiation Toxicity

  11. Occupational exposure to electromagnetic fields and the occurrence of brain tumors. An analysis of possible associations

    SciTech Connect

    Lin, R.S.; Dischinger, P.C.; Conde, J.; Farrell, K.P.

    1985-06-01

    To explore the association between occupation and the occurrence of brain tumor, an epidemiologic study was conducted using data from the death certificates of 951 adult white male Maryland residents who died of brain tumor during the period 1969 through 1982. Compared with the controls, men employed in electricity-related occupations, such as electrician, electric or electronic engineer, and utility company serviceman, were found to experience a significantly higher proportion of primary brain tumors. An increase in the odds ratio for brain tumor was found to be positively related to electromagnetic (EM) field exposure levels. Furthermore, the mean age at death was found to be significantly younger among cases in the presumed high EM-exposure group. These findings suggest that EM exposure may be associated with the pathogenesis of brain tumors, particularly in the promoting stage.

  12. Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy.

    PubMed

    Morrone, Fernanda B; Gehring, Marina P; Nicoletti, Natália F

    2016-09-01

    Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calcium-permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca(2+) activity plays an important role in the regulation of cell proliferation, and Ca(2+) signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca(2+) by modulating the driving force for Ca(2+) entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca(2+)-influx and an indirect activator of voltage-gated Ca(2+)-channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca(2+), and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas. PMID:27418672

  13. Magnetic resonance spectroscopy for detection of choline kinase inhibition in the treatment of brain tumors

    PubMed Central

    Kumar, Manoj; Arlauckas, Sean P.; Saksena, Sona; Verma, Gaurav; Ittyerah, Ranjit; Pickup, Stephen; Popov, Anatoliy V.; Delikatny, Edward J.; Poptani, Harish

    2015-01-01

    Abnormal choline metabolism is a hallmark of cancer and is associated with oncogenesis and tumor progression. Increased choline is consistently observed in both pre-clinical tumor models and in human brain tumors by proton magnetic resonance spectroscopy (MRS). Thus, inhibition of choline metabolism using specific choline kinase inhibitors such as MN58b may be a promising new strategy for treatment of brain tumors. We demonstrate the efficacy of MN58b in suppressing phosphocholine production in three brain tumor cell lines. In vivo MRS studies of rats with intra-cranial F98-derived brain tumors showed a significant decrease in tumor total choline concentration after treatment with MN58b. High resolution MRS of tissue extracts confirmed that this decrease was due to a significant reduction in phosphocholine. Concomitantly, a significant increase in poly-unsaturated lipid resonances was also observed in treated tumors, indicating apoptotic cell death. Magnetic resonance imaging (MRI) based volume measurements demonstrated a significant growth arrest in the MN58b-treated tumors in comparison to saline-treated controls. Histologically, MN58b-treated tumors showed decreased cell density, as well as increased apoptotic cells. These results suggest that inhibition of choline kinase can be used as an adjuvant to chemotherapy in the treatment of brain tumors and that decreases in total choline observed by MRS can be used as an effective phamacodynamic biomarker of treatment response. PMID:25657334

  14. 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

  15. Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

    ClinicalTrials.gov

    2013-05-01

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac 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; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  16. Invited review--neuroimaging response assessment criteria for brain tumors in veterinary patients.

    PubMed

    Rossmeisl, John H; Garcia, Paulo A; Daniel, Gregory B; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos; Klahn, Shawna

    2014-01-01

    The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria. PMID:24219161

  17. INVITED REVIEW – NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

    PubMed Central

    Rossmeisl, John H.; Garcia, Paulo A.; Daniel, Gregory B.; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos; Klahn, Shawna

    2013-01-01

    The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the Response Evaluation Criteria in Solid Tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and Response Assessment in Neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR-imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria. PMID:24219161

  18. A multicenter study of primary brain tumor incidence in Australia (2000–2008)

    PubMed Central

    Dobes, Martin; Shadbolt, Bruce; Khurana, Vini G.; Jain, Sanjiv; Smith, Sarah F.; Smee, Robert; Dexter, Mark; Cook, Raymond

    2011-01-01

    There are conflicting reports from Europe and North America regarding trends in the incidence of primary brain tumor, whereas the incidence of primary brain tumors in Australia is currently unknown. We aimed to determine the incidence in Australia with age-, sex-, and benign-versus-malignant histology-specific analyses. A multicenter study was performed in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), which has a combined population of >7 million with >97% rate of population retention for medical care. We retrospectively mined pathology databases servicing neurosurgical centers in NSW and ACT for histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008. Data were weighted for patient outflow and data completeness. Incidence rates were age standardized and trends analyzed using joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed. The overall US-standardized incidence of primary brain tumors was 11.3 cases 100 000 person-years (±0.13; 95% confidence interval, 9.8–12.3) during the study period with no significant linear increase. A significant increase in primary malignant brain tumors from 2000 to 2008 was observed; this appears to be largely due to an increase in malignant tumor incidence in the ≥65-year age group. This collection represents the most contemporary data on primary brain tumor incidence in Australia. Whether the observed increase in malignant primary brain tumors, particularly in persons aged ≥65 years, is due to improved detection, diagnosis, and care delivery or a true change in incidence remains undetermined. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence that can be independent of multiple interstate cancer registries. PMID:21727214

  19. Penetration of intra-arterially administered vincristine in experimental brain tumor1,2

    PubMed Central

    Boyle, Frances M.; Eller, Susan L.; Grossman, Stuart A.

    2004-01-01

    Vincristine is an integral part of the “PCV” regimen that is commonly administered to treat primary brain tumors. The efficacy of vincristine as a single agent in these tumors has been poorly studied. This study was designed to determine whether vincristine enters normal rat brain or an intracranially or subcutaneously implanted glioma and to assess the presence of the efflux pump P-glycoprotein (P-gp) on tumor and vascular endothelial cells. The 9L rat gliosarcoma was implanted intracranially and subcutaneously in three Fischer 344 rats. On day 7, [3H]vincristine (50 μCi, 4.8 μg) was injected into the carotid artery, and the animals were euthanized 10 or 20 min later. Quantitative autoradiography revealed that vincristine levels in the liver were 6- to 11-fold greater than in the i.c. tumor, and 15- to 37-fold greater than in normal brain, the reverse of the expected pattern with intra-arterial delivery. Vincristine levels in the s.c. tumor were 2-fold higher than levels in the i.c. tumor. P-gp was detected with JSB1 antibody in vascular endothelium of both normal brain and the i.c. tumor, but not in the tumor cells in either location, or in endothelial cells in the s.c. tumor. These results demonstrate that vincristine has negligible penetration of normal rat brain or i.c. 9L glioma despite intra-arterial delivery and the presence of blood-brain barrier dysfunction as demonstrated by Evan’s blue. Furthermore, this study suggests that P-gp-mediated efflux from endothelium may explain these findings. The lack of penetration of vincristine into brain tumor and the paucity of single-agent activity studies suggest that vincristine should not be used in the treatment of primary brain tumors. PMID:15494097

  20. Regional blood-to-tissue transport in RT-9 brain tumors.

    PubMed

    Molnar, P; Blasberg, R G; Horowitz, M; Smith, B; Fenstermacher, J

    1983-06-01

    Regional blood-to-tissue transport, expressed as a unidirectional transfer rate constant (K), was measured in experimental RT-9 brain tumors using 14C-alpha-aminoisobutyric acid (AIB) and quantitative autoradiographic techniques. The magnitude of K depends on the permeability, surface area, and blood flow of the tissue capillaries. The transfer rate constant was variable within tumor tissue (range 0.001 to 0.178 ml/gm/min) and depended on tumor size, location (intraparenchymal, meningeal, or choroid plexus associated), and to a lesser extent on necrosis and cyst formation. Brain adjacent to tumor had higher K values, particularly around larger tumors (0.004 to 0.014 ml/gm/min), than corresponding brain regions in the contralateral hemisphere (0.001 to 0.002 ml/gm/min). Estimates of the fractional extraction of AIB by intraparenchymal tumors were between 0.008 and 0.4 ml/gm/min. Values of fractional extraction in this range indicate that tumor capillaries are not freely permeable to this solute. The values of K measured with AIB in this study, for the most part, approximate the permeability-surface area product of tumor and brain capillaries. The experimental data suggest that the permeability-surface area characteristics of the microvasculature in small RT-9 tumors are similar to those of the host tissue, whereas the microvasculature of larger RT-9 tumors is influenced more by intrinsic tumor factors.

  1. 18F-FDG PET and MR Imaging Associations Across a Spectrum of Pediatric Brain Tumors: A Report from the Pediatric Brain Tumor Consortium

    PubMed Central

    Zukotynski, Katherine; Fahey, Frederic; Kocak, Mehmet; Kun, Larry; Boyett, James; Fouladi, Maryam; Vajapeyam, Sridhar; Treves, Ted; Poussaint, Tina Y.

    2014-01-01

    The purpose of this study was to describe 18F-FDG uptake across a spectrum of pediatric brain tumors and correlate 18F-FDG PET with MR imaging variables, progression-free survival (PFS), and overall survival (OS). Methods A retrospective analysis was conducted of children enrolled in phase I/II clinical trials through the Pediatric Brain Tumor Consortium from August 2000 to June 2010. PET variables were summarized within diagnostic categories using descriptive statistics. Associations of PET with MR imaging variables and PFS and OS by tumor types were evaluated. Results Baseline 18F-FDG PET was available in 203 children; 66 had newly diagnosed brain tumors, and 137 had recurrent/refractory brain tumors before enrolling in a Pediatric Brain Tumor Consortium trial. MR imaging was performed within 2 wk of PET and before therapy in all cases. The 18F-FDG uptake pattern and MR imaging contrast enhancement (CE) varied by tumor type. On average, glioblastoma multiforme and medulloblastoma had uniform, intense uptake throughout the tumor, whereas brain stem gliomas (BSGs) had low uptake in less than 50% of the tumor and ependymoma had low uptake throughout the tumor. For newly diagnosed BSG, correlation of 18F-FDG uptake with CE portended reduced OS (P = 0.032); in refractory/recurrent BSG, lack of correlation between 18F-FDG uptake and CE suggested decreased PFS (P = 0.023). In newly diagnosed BSG for which more than 50% of the tumor had 18F-FDG uptake, there was a suggestion of lower apparent diffusion coefficient (P = 0.061) and decreased PFS (P = 0.065). Conclusion 18F-FDG PET and MR imaging showed a spectrum of patterns depending on tumor type. In newly diagnosed BSG, the correlation of 18F-FDG uptake and CE suggested decreased OS, likely related to more aggressive disease. When more than 50% of the tumor had 18F-FDG uptake, the apparent diffusion coefficient was lower, consistent with increased cellularity. In refractory/recurrent BSG, poor correlation between 18F

  2. Neonatal vitamin D and childhood brain tumor risk.

    PubMed

    Bhatti, Parveen; Doody, David R; Mckean-Cowdin, Roberta; Mueller, Beth A

    2015-05-15

    Vitamin D deficiency among pregnant women is common. Compelling animal evidence suggests carcinogenic effects of vitamin D deficiency on the brains of offspring; however, the impact of circulating vitamin D [25(OH)D] on childhood brain tumor (CBT) risk has not been previously evaluated. Using linked birth-cancer registry data in Washington State, 247 CBT cases (<15 years at diagnosis; born 1991 or later) were identified. A total of 247 birth year-, sex- and race-matched controls were selected from the remaining birth certificates. Liquid chromatography-tandem mass spectrometry was used to measure circulating levels of vitamin D3 [25(OH)D3] in neonatal dried blood spots. Overall, no significant associations were observed. However, when stratified by median birth weight (3,458 g), there was evidence of increasing risk of CBT with increasing 25(OH)D3 among children in the higher birth weight category. Compared to the lowest quartile (2.8-7.7 ng/mL), odds ratios (ORs) and 95% confidence intervals (CIs) for the second (7.7-<11.0 ng/mL), third (11.0-<14.7 ng/mL) and fourth (14.7-37.0) quartiles of 25(OH)D3 were 1.7 (1.0-3.3), 2.4 (1.2-4.8) and 2.6 (1.2-5.6), respectively. Among children in the lower birth weight category, there was suggestive evidence of a protective effect: ORs and 95% CIs for the second, third and fourth quartiles were 0.9 (0.4-1.9), 0.7 (0.3-1.4) and 0.6 (0.3-1.3), respectively. Any associations of neonatal vitamin D with CBT may be birth weight-specific, suggesting the possible involvement of insulin-like growth factor 1, circulating levels of which have been associated with vitamin D and accelerated fetal growth.

  3. Preclinical impact of bevacizumab on brain and tumor distribution of irinotecan and temozolomide.

    PubMed

    Goldwirt, Lauriane; Beccaria, Kevin; Carpentier, Alexandre; Idbaih, Ahmed; Schmitt, Charlotte; Levasseur, Camille; Labussiere, Marianne; Milane, Aline; Farinotti, Robert; Fernandez, Christine

    2015-04-01

    Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Prognosis of GBM patients is poor with median overall survival around 15 months. Temozolomide is the chemotherapeutic agent used in the standard of care of newly diagnosed GBM patients relying on radiotherapy with concurrent chemotherapy followed by chemotherapy alone. Irinotecan has shown some efficacy in recurrent malignant gliomas. Bevacizumab has been combined with irinotecan in the treatment of recurrent GBM and with temozolomide in newly diagnosed GBM. As the efficacy of GBM treatments relies on their brain distribution through the blood brain barrier, the aim of the present preclinical work was to study, in in vivo models, the impact of bevacizumab on brain and tumor distribution of temozolomide and irinotecan. Our results show that bevacizumab pre-treatment was associated with a reduced temozolomide brain distribution in tumor-free mice. In tumor bearing mice, bevacizumab increased temozolomide tumor distribution, although not statistically significant. In both tumor-free and tumor-bearing mice, bevacizumab does not modify brain distribution of irinotecan and its metabolite SN-38. Bevacizumab impacts brain distribution of some anti-tumor drugs and potentially their efficacy in GBM. Further studies are warranted to investigate other therapeutic combination.

  4. Molecular imaging of brain tumors with 18F-DOPA PET and PET/CT.

    PubMed

    Calabria, Ferdinando; Chiaravalloti, Agostino; Di Pietro, Barbara; Grasso, Cristina; Schillaci, Orazio

    2012-06-01

    The objective of this study was to give an overview of the potential clinical utility of [18F]-L-dihydroxyphenylalanine (18F-DOPA) PET and PET/CT for imaging of brain tumors. Review articles and reference lists were used to supplement the search findings. 18F-DOPA has been investigated as a PET tracer for primary brain tumors, metastases of somatic cancer, and evaluation of relapse of pathology in patients with brain tumor after surgery and/or radiotherapy on the basis of enhanced cell proliferation. Available studies have provided encouraging preliminary results for diagnosis of brain tumors and relapse after surgery/radiotherapy. In the brain, excellent discrimination between tumor and normal tissue can be achieved because of the low physiological uptake of 18F-DOPA and the high ratio between tumor and normal hemispheric tissue. Information on evaluation of brain metastases is limited but encouraging. PET and PET/CT with 18F-DOPA are useful in diagnosing primary brain tumors and should be recommended in the diagnosis of relapse of disease after surgical treatment and/or radiotherapy. Semiquantitative analysis could improve diagnosis while correlative imaging with MRI is essential. Limits are due to low knowledge of potential pitfalls.

  5. Awake brain tumor resection during pregnancy: Decision making and technical nuances.

    PubMed

    Meng, Lingzhong; Han, Seunggu J; Rollins, Mark D; Gelb, Adrian W; Chang, Edward F

    2016-02-01

    The co-occurrence of primary brain tumor and pregnancy poses unique challenges to the treating physician. If a rapidly growing lesion causes life-threatening mass effect, craniotomy for tumor debulking becomes urgent. The choice between awake craniotomy versus general anesthesia becomes complicated if the tumor is encroaching on eloquent brain because considerations pertinent to both patient safety and oncological outcome, in addition to fetal wellbeing, are involved. A 31-year-old female at 30 weeks gestation with twins presented to our hospital seeking awake craniotomy to resect a 7 × 6 × 5 cm left frontoparietal brain tumor with 7 mm left-to-right subfalcine herniation on imaging that led to word finding difficulty, dysfluency, right upper extremity paralysis, and right lower extremity weakness. She had twice undergone tumor debulking under general anesthesia during the same pregnancy at an outside hospital at 16 weeks and 28 weeks gestation. There were considerations both for and against awake brain tumor resection over surgery under general anesthesia. The decision-making process and the technical nuances related to awake brain tumor resection in this neurologically impaired patient are discussed. Awake craniotomy benefits the patient who harbors a tumor that encroaches on the eloquent brain by allowing a greater extent of resection while preserving the language and sensorimotor function. It can be successfully done in pregnant patients who are neurologically impaired. The patient should be motivated and well informed of the details of the process. A multidisciplinary and collaborative effort is also crucial.

  6. 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.

  7. The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor.

    PubMed

    Valvona, Cara J; Fillmore, Helen L; Nunn, Peter B; Pilkington, Geoffrey J

    2016-01-01

    There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations. Lactate dehydrogenase A (LDHA) is a cytosolic enzyme, predominantly involved in anaerobic and aerobic glycolysis (the Warburg effect); however, it has multiple additional functions in non-neoplastic and neoplastic tissues, which are not commonly known or discussed. This review summarizes what is currently known about the function of LDHA and identifies areas that would benefit from further exploration. The current knowledge of the role of LDHA in the brain and its potential as a therapeutic target for brain tumors will also be highlighted. The Warburg effect appears to be universal in tumors, including primary brain tumors, and LDHA (because of its involvement with this process) has been identified as a potential therapeutic target. Currently, there are, however, no suitable LDHA inhibitors available for tumor therapies in the clinic.

  8. Awake brain tumor resection during pregnancy: Decision making and technical nuances.

    PubMed

    Meng, Lingzhong; Han, Seunggu J; Rollins, Mark D; Gelb, Adrian W; Chang, Edward F

    2016-02-01

    The co-occurrence of primary brain tumor and pregnancy poses unique challenges to the treating physician. If a rapidly growing lesion causes life-threatening mass effect, craniotomy for tumor debulking becomes urgent. The choice between awake craniotomy versus general anesthesia becomes complicated if the tumor is encroaching on eloquent brain because considerations pertinent to both patient safety and oncological outcome, in addition to fetal wellbeing, are involved. A 31-year-old female at 30 weeks gestation with twins presented to our hospital seeking awake craniotomy to resect a 7 × 6 × 5 cm left frontoparietal brain tumor with 7 mm left-to-right subfalcine herniation on imaging that led to word finding difficulty, dysfluency, right upper extremity paralysis, and right lower extremity weakness. She had twice undergone tumor debulking under general anesthesia during the same pregnancy at an outside hospital at 16 weeks and 28 weeks gestation. There were considerations both for and against awake brain tumor resection over surgery under general anesthesia. The decision-making process and the technical nuances related to awake brain tumor resection in this neurologically impaired patient are discussed. Awake craniotomy benefits the patient who harbors a tumor that encroaches on the eloquent brain by allowing a greater extent of resection while preserving the language and sensorimotor function. It can be successfully done in pregnant patients who are neurologically impaired. The patient should be motivated and well informed of the details of the process. A multidisciplinary and collaborative effort is also crucial. PMID:26498092

  9. Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape.

    PubMed

    Gajjar, Amar; Bowers, Daniel C; Karajannis, Matthias A; Leary, Sarah; Witt, Hendrik; Gottardo, Nicholas G

    2015-09-20

    Pediatric neuro-oncology has undergone an exciting and dramatic transformation during the past 5 years. This article summarizes data from collaborative group and institutional trials that have advanced the science of pediatric brain tumors and survival of patients with these tumors. Advanced genomic analysis of the entire spectrum of pediatric brain tumors has heralded an era in which stakeholders in the pediatric neuro-oncology community are being challenged to reconsider their current research and diagnostic and treatment strategies. The incorporation of this new information into the next-generation treatment protocols will unleash new challenges. This review succinctly summarizes the key advances in our understanding of the common pediatric brain tumors (ie, medulloblastoma, low- and high-grade gliomas, diffuse intrinsic pontine glioma, and ependymoma) and some selected rare tumors (ie, atypical teratoid/rhabdoid tumor and CNS primitive neuroectodermal tumor). The potential impact of this new information on future clinical protocols also is discussed. Cutting-edge genomics technologies and the information gained from such studies are facilitating the identification of molecularly defined subgroups within patients with particular pediatric brain tumors. The number of evaluable patients in each subgroup is small, particularly in the subgroups of rare diseases. Therefore, international collaboration will be crucial to draw meaningful conclusions about novel approaches to treating pediatric brain tumors.

  10. Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape.

    PubMed

    Gajjar, Amar; Bowers, Daniel C; Karajannis, Matthias A; Leary, Sarah; Witt, Hendrik; Gottardo, Nicholas G

    2015-09-20

    Pediatric neuro-oncology has undergone an exciting and dramatic transformation during the past 5 years. This article summarizes data from collaborative group and institutional trials that have advanced the science of pediatric brain tumors and survival of patients with these tumors. Advanced genomic analysis of the entire spectrum of pediatric brain tumors has heralded an era in which stakeholders in the pediatric neuro-oncology community are being challenged to reconsider their current research and diagnostic and treatment strategies. The incorporation of this new information into the next-generation treatment protocols will unleash new challenges. This review succinctly summarizes the key advances in our understanding of the common pediatric brain tumors (ie, medulloblastoma, low- and high-grade gliomas, diffuse intrinsic pontine glioma, and ependymoma) and some selected rare tumors (ie, atypical teratoid/rhabdoid tumor and CNS primitive neuroectodermal tumor). The potential impact of this new information on future clinical protocols also is discussed. Cutting-edge genomics technologies and the information gained from such studies are facilitating the identification of molecularly defined subgroups within patients with particular pediatric brain tumors. The number of evaluable patients in each subgroup is small, particularly in the subgroups of rare diseases. Therefore, international collaboration will be crucial to draw meaningful conclusions about novel approaches to treating pediatric brain tumors. PMID:26304884

  11. NI-78LABEL-FREE MULTIPHOTON MICROSCOPY: A NOVEL TOOL FOR THE IMAGING OF BRAIN TUMORS

    PubMed Central

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

    2014-01-01

    Changes in tissue composition caused by brain tumor growth involve a series of complex biochemical alterations which can be imaged on unstained native tissue using multiphoton microscopy: We used coherent anti-Stokes Raman scattering (CARS) imaging that resonantly excites the symmetric stretching vibration of CH2 groups at 2850 cm−1 and visualizes lipid content in combination with imaging of endogenous two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) to discern different types of tumors from normal tissue in unstained, native brain samples. Experimental brain tumors were induced in nude mice NMRI nu/nu (n = 25) by stereotactic implantation of glioblastoma (U87), melanoma (A375) and breast cancer (MCF-7) cell lines. Label-free multiphoton microscopy of brain cryosections provided exhaustive information of the tumor morphochemistry. The tumor border was defined with cellular resolution by a strong reduction of CARS signal intensity to 61% (glioblastoma), 71% (melanoma) and 68% (breast cancer). This reduction of lipid content within the tumor was confirmed by Raman spectroscopy. Micrometastases infiltrating normal tissue (size 50 - 200 µm) were identified in glioblastoma and melanoma. Additionally, multiphoton microscopy proved a reduction of CARS signal intensity in all human glioblastoma samples analyzed (to 72%, n = 6). Additionally, relevant SHG and TPEF signals were detected in human primary and secondary brain tumor samples and enabled to image variations in tumor associated vasculature, fibrosis, necrosis and nuclear size and density. All primary or secondary brain tumors investigated were characterized by a lower intensity of the CARS signal, therefore offering a simple tool for objective tumor detection and delineation. The combination of techniques allows retrieving a quantity of information on native unstained tissue which is comparable to H&E staining. Therefore, label-free multiphoton microscopy has the potential to become a

  12. Determination of intra-axial brain tumors cellularity through the analysis of T2 Relaxation time of brain tumors before surgery using MATLAB software

    PubMed Central

    Abdolmohammadi, Jamil; Shafiee, Mohsen; Faeghi, Fariborz; Arefan, Douman; Zali, Alireza; Motiei-Langroudi, Rouzbeh; Farshidfar, Zahra; Nazarlou, Ali Kiani; Tavakkoli, Ali; Yarham, Mohammad

    2016-01-01

    Introduction Timely diagnosis of brain tumors could considerably affect the process of patient treatment. To do so, para-clinical methods, particularly MRI, cannot be ignored. MRI has so far answered significant questions regarding tumor characteristics, as well as helping neurosurgeons. In order to detect the tumor cellularity, neuro-surgeons currently have to sample specimens by biopsy and then send them to the pathology unit. The aim of this study is to determine the tumor cellularity in the brain. Methods In this cross-sectional study, 32 patients (18 males and 14 females from 18–77 y/o) were admitted to the neurosurgery department of Shohada-E Tajrish Hospital in Tehran, Iran from April 2012 to February 2014. In addition to routine pulse sequences, T2W Multi echo pulse sequences were taken and the images were analyzed using the MATLAB software to determine the brain tumor cellularity, compared with the biopsy Results These findings illustrate the need for more T2 relaxation time decreases, the higher classes of tumors will stand out in the designed table. In this study, the results show T2 relaxation time with a 85% diagnostic weight, compared with the biopsy, to determine the brain tumor cellularity (p<0.05). Conclusion Our results indicate that the T2 relaxation time feature is the best method to distinguish and present the degree of intra-axial brain tumors cellularity (85% accuracy compared to biopsy). The use of more data is recommended in order to increase the percent accuracy of this techniques. PMID:27757181

  13. [A brain tumor automatic assisted-diagnostic system based on medical image shape analysis].

    PubMed

    Wang, Li-Li; Yang, Jie

    2005-03-01

    This paper covers a brain tumor assisted diagnosis system based on medical image analysis. The system supplements the PACS functions such as display of medical images and database inquiry, segments slice in real-time using the algorithm of fuzzy region competition, extracts shape feature factors such as contour label, compactness, moment, Fourier Descriptor, chord length, radius and other medical data on the brain tumor image with irregular contour feature after segmentation and then feeds to Bayesian network in order to sort the brain tumor for the implementation of automatic assisted diagnosis. PMID:16011110

  14. [Graph-based interactive three-dimensional segmentation of magnetic resonance images of brain tumors].

    PubMed

    Li, Wei; Chen, Wu-fan

    2009-01-01

    We propose a graph-based three-dimensional (3D) algorithm to automatically segment brain tumors from magnetic resonance images (MRI). The algorithm uses minimum s/t cut criteria to obtain a global optimal result of objective function formed according to Markov Random Field Model and Maximum a posteriori (MAP-MRF) theory, and by combining the expectation-maximization (EM) algorithm to estimate the parameters of mixed Gaussian model for normal brain and tumor tissues. 3D segmentation results of brain tumors are fast achieved by our algorithm. The validation of the algorithm was tested and showed good accuracy and adaptation under simple interactions with the physicians. PMID:19218135

  15. [Two Surgical Techniques for Metastatic Brain Tumors:Minimum Resection and Removal with Safety Margin].

    PubMed

    Nakasu, Yoko; Mitsuya, Koichi; Hayashi, Nakamasa; Ito, Ichiro

    2016-03-01

    Successful resection of cerebral metastases is based on good basic neurosurgical techniques, in conjunction with technologies for tumor localization. A clear understanding about the border zone pathology of metastatic lesions leads to two different techniques for safe and effective tumor removal. There is no capsule or pseudocapsule around the metastatic brain tumors. The border zone is widely heterogeneous, especially in lesions after stereotactic irradiation. Resection can be performed in a circumferential and en bloc fashion with sufficient safety margin of the normal brain in non-eloquent area. However, enucleation should be done without surrounding brain damage in and near eloquent areas.

  16. 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.

  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. Cellular microenvironment modulates the galvanotaxis of brain tumor initiating cells

    PubMed Central

    Huang, Yu-Ja; Hoffmann, Gwendolyn; Wheeler, Benjamin; Schiapparelli, Paula; Quinones-Hinojosa, Alfredo; Searson, Peter

    2016-01-01

    Galvanotaxis is a complex process that represents the collective outcome of various contributing mechanisms, including asymmetric ion influxes, preferential activation of voltage-gated channels, and electrophoretic redistribution of membrane components. While a large number of studies have focused on various up- and downstream signaling pathways, little is known about how the surrounding microenvironment may interact and contribute to the directional response. Using a customized galvanotaxis chip capable of carrying out experiments in both two- and three-dimensional microenvironments, we show that cell-extracellular matrix (ECM) interactions modulate the galvanotaxis of brain tumor initiating cells (BTICs). Five different BTICs across three different glioblastoma subtypes were examined and shown to all migrate toward the anode in the presence of a direct-current electric field (dcEF) when cultured on a poly-L-ornithine/laminin coated surface, while the fetal-derived neural progenitor cells (fNPCs) migrated toward the cathode. Interestingly, when embedded in a 3D ECM composed of hyaluronic acid and collagen, BTICs exhibited opposite directional response and migrated toward the cathode. Pharmacological inhibition against a panel of key molecules involved in galvanotaxis further revealed the mechanistic differences between 2- and 3D galvanotaxis in BTICs. Both myosin II and phosphoinositide 3-kinase (PI3K) were found to hold strikingly different roles in different microenvironments. PMID:26898606

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

    PubMed

    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

    2016-05-01

    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.

  20. [Cognitive functions and personality traits in patients with brain tumors: the role of lesion localization].

    PubMed

    Razumnikova, O M; Perfil'ev, A M; Stupak, V V

    2014-01-01

    Personality traits and cognitive functions were studied depending on a tumor localization in the brain in 21 neurosurgical patients and the results were compared with a control group. In patients with brain damage, mostly affected were personality traits associated with emotion regulation and social interaction (neuroticism, psychoticism and social conformity). Increases in psychoticism and decreases in neuroticism were more expressed in patients with a left-hemisphere localization of tumors. The tumor-induced decrease in cognitive abilities was more presented in performing figurative tasks and less in verbal ones. Verbal functions were more decreased in the group with frontal localization of tumor compared to that with parietal localization.

  1. 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

  2. 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

  3. Selective ablation of rat brain tumors by boron neutron capture therapy

    SciTech Connect

    Coderre, J.; Joel, D. ); Rubin, P.; Freedman, A.; Hansen, J.; Wooding, T.S. Jr.; Gash, D. )

    1994-03-30

    Damage to the surrounding normal brain tissue limits the amount of radiation that can be delivered to intracranial tumors. Boron neutron capture therapy (BNCT) is a binary treatment that allows selective tumor irradiation. This study evaluates the damage imparted to the normal brain during BNCT or x-irradiation. The brains of rats with implanted 9L gliosarcomas were examined 1 year after tumor-curative doses of either 250 kV X-rays or BNCT. Histopathologic techniques included hematoxylin and eosin staining, horseradish peroxidase perfusion, and electron microscopy. Longterm X-ray survivors showed extensive cortical atrophy, loss of neurons, and widespread leakage of the blood-brain barrier (BBB), particularly around the tumor scar. In contrast, the brains and the BBB of longterm BNCT survivors appeared relatively normal under both light- and electron-microscopic examination. Intact blood vessels were observed running directly through the avascular, collagenous tumor scar. The selective therapeutic effect of BNCT is evident in comparison to x-irradiation. Both groups of animals showed no evidence of residual tumor at 1 year. However, with x-irradiation there is no therapeutic ratio and tumor eradication severely injuries the remaining brain parenchyma. These observations indicate a substantial therapeutic gain for BNCT. 50 refs., 8 figs., 1 tab.

  4. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival

    PubMed Central

    Wainwright, Derek A.; Balyasnikova, Irina V.; Chang, Alan L.; Ahmed, Atique U.; Moon, Kyung-Sub; Auffinger, Brenda; Tobias, Alex L.; Han, Yu; Lesniak, Maciej S.

    2012-01-01

    Purpose Glioblastoma multiforme (GBM) is an aggressive adult brain tumor with a poor prognosis. One hallmark of GBM is the accumulation of immunosuppressive and tumor-promoting CD4+FoxP3+GITR+ regulatory T cells (Tregs). Here, we investigated the role of indoleamine 2,3 dioxygenase (IDO) in brain tumors and the impact on Treg recruitment. Experimental Design To determine the clinical relevance of IDO expression in brain tumors, we first correlated patient survival to the level of IDO expression from resected glioma specimens. We also used novel orthotopic and transgenic models of glioma to study how IDO affects Tregs. The impact of tumor-derived and peripheral IDO expression on Treg recruitment, GITR expression and long-term survival was determined. Results Downregulated IDO expression in glioma predicted a significantly better prognosis in patients. Co-incidently, both IDO -competent and -deficient mice showed a survival advantage bearing IDO-deficient brain tumors, when compared to IDO-competent brain tumors. Moreover, IDO-deficiency was associated with a significant decrease in brain-resident Tregs, both in orthotopic and transgenic mouse glioma models. IDO-deficiency was also associated with lower GITR expression levels on Tregs. Interestingly, the long-term survival advantage conferred by IDO-deficiency was lost in T cell-deficient mice. Conclusions These clinical and pre-clinical data confirm that IDO expression increases the recruitment of immunosuppressive Tregs which leads to tumor outgrowth. In contrast, IDO deficiency decreases Treg recruitment and enhances T cell-mediated tumor rejection. Thus, the data suggest a critical role for IDO-mediated immunosuppression in glioma and supports the continued investigation of IDO-Treg interactions in the context of brain tumors. PMID:22932670

  5. Molecular genetics of pediatric brain stem gliomas. Application of PCR techniques to small and archival brain tumor specimens

    SciTech Connect

    Louis, D.N.; Rubio, M.P.; Correa, K.M.; Gusella, J.F.; Deimling, A. von )

    1993-09-01

    Brain stem gliomas are pediatric astrocytomas that histologically resemble adult supratentorial astrocytomas such as gliobastomas multiforme (GBM). The molecular genetic studies have suggested that adult GBM can be divided into two genetic subsets: Tumors with p53 tumor suppressor gene mutations and chromosome 17p loss that occur more commonly in younger patients; and tumors with epidermal growth factor receptor (EGFR) gene amplification that occur more commonly in older patients. Brain stem gliomas have not been studied since biopsies of these tumors are rare and extremely small. The authors investigated the molecular genetic composition of seven brain stem glioblastomas (two small biopsies, five autopsies) using polymerase chain reaction (PCR) assays for chromosomal loss, gene mutation and gene amplification. Four cases lost portions of chromosome 17p that included the 53p gene. These four cases and one additional case had mutations in the p53 gene. None of the cases showed amplification of the EGFR gene. Allelic losses of the long arm of chromosome 10 were noted in four cases. These results suggest similarities between pediatric brain stem glioblastomas and those GBM that occur in younger adult patients, and confirm the utility of PCR-based means of studying small and archival brain tumor specimens. 47 refs., 7 figs., 2 tabs.

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

    PubMed

    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. PMID:23743802

  7. Emerging Techniques in Brain Tumor Imaging: What Radiologists Need to Know.

    PubMed

    Kim, Minjae; Kim, Ho Sung

    2016-01-01

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response.

  8. What Are the Risk Factors for Brain and Spinal Cord Tumors in Children?

    MedlinePlus

    ... associated with cranial or spinal nerve schwannomas, especially vestibular schwannomas (acoustic neuromas), which almost always occur on ... possible increased risk of brain tumors or of vestibular schwannomas in adults with cell phone use, but ...

  9. Emerging Techniques in Brain Tumor Imaging: What Radiologists Need to Know.

    PubMed

    Kim, Minjae; Kim, Ho Sung

    2016-01-01

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response. PMID:27587949

  10. Combining microbubbles and ultrasound for drug delivery to brain tumors: current progress and overview.

    PubMed

    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.

  11. 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

  12. Emerging Techniques in Brain Tumor Imaging: What Radiologists Need to Know

    PubMed Central

    Kim, Minjae

    2016-01-01

    Among the currently available brain tumor imaging, advanced MR imaging techniques, such as diffusion-weighted MR imaging and perfusion MR imaging, have been used for solving diagnostic challenges associated with conventional imaging and for monitoring the brain tumor treatment response. Further development of advanced MR imaging techniques and postprocessing methods may contribute to predicting the treatment response to a specific therapeutic regimen, particularly using multi-modality and multiparametric imaging. Over the next few years, new imaging techniques, such as amide proton transfer imaging, will be studied regarding their potential use in quantitative brain tumor imaging. In this review, the pathophysiologic considerations and clinical validations of these promising techniques are discussed in the context of brain tumor characterization and treatment response. PMID:27587949

  13. Neonatal Vitamin D and Childhood Brain Tumor Risk

    PubMed Central

    Bhatti, Parveen; Doody, David R.; Mckean-Cowdin, Roberta; Mueller, Beth A.

    2014-01-01

    Vitamin D deficiency among pregnant women is common. Compelling animal evidence suggests carcinogenic effects of vitamin D deficiency on the brains of offspring; however the impact of circulating vitamin D [25(OH)D] on childhood brain tumor (CBT) risk has not been previously evaluated. Using linked birth-cancer registry data in Washington State, 247 CBT cases (< 15 years at diagnosis; born 1991 or later) were identified. 247 birth year, sex and race-matched controls were selected from the remaining birth certificates. Liquid chromatography-tandem mass spectrometry was used to measure circulating levels of vitamin D3 [25-(OH)D3] in neonatal dried blood spots. Overall, no significant associations were observed. However, when stratified by median birth weight (3,458 grams), there was evidence of increasing risk of CBT with increasing 25-(OH)D3 among children in the higher birth weight category. Compared to the lowest quartile (2.8-7.7 ng/mL), odds ratios (OR) and 95% Confidence Intervals (CI) for the 2nd (7.7-< 11.0 ng/mL), 3rd (11.0-<14.7 ng/mL) and 4th (14.7-37.0) quartiles of 25-(OH)D3 were 1.7 (1.0-3.3), 2.4 (1.2-4.8) and 2.6 (1.2-5.6), respectively. Among children in the lower birth weight category, there was suggestive evidence of a protective effect: ORs and 95% CI for the 2nd, 3rd and 4th quartiles were 0.9 (0.4-1.9), 0.7 (0.3-1.4) and 0.6 (0.3-1.3), respectively. Any associations of neonatal vitamin D with CBT may be birth weight-specific, suggesting the possible involvement of insulin-like growth factor 1 (IGF-1), circulating levels of which have been associated with vitamin D and accelerated fetal growth. PMID:25348494

  14. Multimodality Brain Tumor Imaging: MR Imaging, PET, and PET/MR Imaging.

    PubMed

    Fink, James R; Muzi, Mark; Peck, Melinda; Krohn, Kenneth A

    2015-10-01

    Standard MR imaging and CT are routinely used for anatomic diagnosis in brain tumors. Pretherapy planning and posttreatment response assessments rely heavily on gadolinium-enhanced MR imaging. Advanced MR imaging techniques and PET imaging offer physiologic, metabolic, or functional information about tumor biology that goes beyond the diagnostic yield of standard anatomic imaging. With the advent of combined PET/MR imaging scanners, we are entering an era wherein the relationships among different elements of tumor metabolism can be simultaneously explored through multimodality MR imaging and PET imaging. The purpose of this review is to provide a practical and clinically relevant overview of current anatomic and physiologic imaging of brain tumors as a foundation for further investigations, with a primary focus on MR imaging and PET techniques that have demonstrated utility in the current care of brain tumor patients.

  15. 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

  16. A versatile ex vivo technique for assaying tumor angiogenesis and microglia in the brain

    PubMed Central

    Ghoochani, Ali; Yakubov, Eduard; Sehm, Tina; Fan, Zheng; Hock, Stefan; Buchfelder, Michael

    2016-01-01

    Primary brain tumors are hallmarked for their destructive activity on the microenvironment and vasculature. However, solely few experimental techniques exist to access the tumor microenvironment under anatomical intact conditions with remaining cellular and extracellular composition. Here, we detail an ex vivo vascular glioma impact method (VOGIM) to investigate the influence of gliomas and chemotherapeutics on the tumor microenvironment and angiogenesis under conditions that closely resemble the in vivo situation. We generated organotypic brain slice cultures from rats and transgenic mice and implanted glioma cells expressing fluorescent reporter proteins. In the VOGIM, tumor-induced vessels presented the whole range of vascular pathologies and tumor zones as found in human primary brain tumor specimens. In contrast, non-transformed cells such as primary astrocytes do not alter the vessel architecture. Vascular characteristics with vessel branching, junctions and vessel length are quantitatively assessable as well as the peritumoral zone. In particular, the VOGIM resembles the brain tumor microenvironment with alterations of neurons, microglia and cell survival. Hence, this method allows live cell monitoring of virtually any fluorescence-reporter expressing cell. We further analyzed the vasculature and microglia under the influence of tumor cells and chemotherapeutics such as Temozolamide (Temodal/Temcad®). Noteworthy, temozolomide normalized vasculare junctions and branches as well as microglial distribution in tumor-implanted brains. Moreover, VOGIM can be facilitated for implementing the 3Rs in experimentations. In summary, the VOGIM represents a versatile and robust technique which allows the assessment of the brain tumor microenvironment with parameters such as angiogenesis, neuronal cell death and microglial activity at the morphological and quantitative level. PMID:26673818

  17. Preclinical studies of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in pediatric brain tumors.

    PubMed

    Morfouace, Marie; Nimmervoll, Birgit; Boulos, Nidal; Patel, Yogesh T; Shelat, Anang; Freeman, Burgess B; Robinson, Giles W; Wright, Karen; Gajjar, Amar; Stewart, Clinton F; Gilbertson, Richard J; Roussel, Martine F

    2016-01-01

    Chemotherapies active in preclinical studies frequently fail in the clinic due to lack of efficacy, which limits progress for rare cancers since only small numbers of patients are available for clinical trials. Thus, a preclinical drug development pipeline was developed to prioritize potentially active regimens for pediatric brain tumors spanning from in vitro drug screening, through intracranial and intra-tumoral pharmacokinetics to in vivo efficacy studies. Here, as an example of the pipeline, data are presented for the combination of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in three pediatric brain tumor models. The in vitro activity of nine novel therapies was tested against tumor spheres derived from faithful mouse models of Group 3 medulloblastoma, ependymoma, and choroid plexus carcinoma. Agents with the greatest in vitro potency were then subjected to a comprehensive series of in vivo pharmacokinetic (PK) and pharmacodynamic (PD) studies culminating in preclinical efficacy trials in mice harboring brain tumors. The nucleoside analog 5-fluoro-2'-deoxycytidine (FdCyd) markedly reduced the proliferation in vitro of all three brain tumor cell types at nanomolar concentrations. Detailed intracranial PK studies confirmed that systemically administered FdCyd exceeded concentrations in brain tumors necessary to inhibit tumor cell proliferation, but no tumor displayed a significant in vivo therapeutic response. Despite promising in vitro activity and in vivo PK properties, FdCyd is unlikely to be an effective treatment of pediatric brain tumors, and therefore was deprioritized for the clinic. Our comprehensive and integrated preclinical drug development pipeline should reduce the attrition of drugs in clinical trials. PMID:26518542

  18. 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

  19. 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.

  20. 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

  1. 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

  2. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents.

    PubMed

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors. PMID:23208215

  3. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents

    NASA Astrophysics Data System (ADS)

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

  4. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents.

    PubMed

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

  5. Plasmonics-enhanced and optically modulated delivery of gold nanostars into brain tumor

    PubMed Central

    Yuan, Hsiangkuo; Wilson, Christy M.; Xia, Jun; Doyle, Sarah L.; Li, Shuqin; Fales, Andrew M; Liu, Yang; Ozaki, Ema; Mulfaul, Kelly; Hanna, Gabi; Palmer, Gregory M.; Wang, Lihong V.; Grant, Gerald A.

    2014-01-01

    Plasmonics-active gold nanostars exhibiting strong imaging contrast and efficient photothermal transduction were synthesized for a novel pulsed laser-modulated plasmonics-enhanced brain tumor microvascular permeabilization. We demonstrate a selective, optically modulated delivery of nanoprobes into the tumor parenchyma with minimal off-target distribution. PMID:24619405

  6. Bioluminescence imaging of invasive intracranial xenografts: implications for translational research and targeted therapeutics of brain tumors.

    PubMed

    Dinca, Eduard B; Voicu, Ramona V; Ciurea, Alexandru V

    2010-10-01

    Despite decades of study, the etiology of brain cancer remains elusive. However, extensive molecular characterization of primary brain tumors has been accomplished, outlining recurrent features that are proving useful for devising targeted therapies. There are far too few patients available for comparing the efficacy of therapeutic combinations, especially when variations in dosing, frequency, and sequencing are taken into account. Consequently, there is a substantial need for increasing preclinical testing throughput using clinically relevant models. We review luminescent optical imaging for its potential in facilitating in vivo assessment of intracranial tumor growth and response to therapy in rodent orthotopic xenograft models of primary brain malignancies. We review the rationale behind the need of an in vivo model, why orthotopic tumor models displaying an invasive phenotype may be a superior choice when compared to flank-implanted tumors, and what advantages may be drawn from the use of modified cells, suitable for sequential monitoring by in vivo optical imaging. Studies show that luminescent signal correlates highly both with tumor burden and Kaplan-Meier survival curves of rodents bearing intracranial xenografts. We conclude that bioluminescent imaging is a highly sensitive technique for assessment of tumor burden, response to therapy, tumor recurrence, and behavior to salvage therapy, making it a superior option for longitudinal monitoring in intracranial rodent models of primary brain tumors.

  7. Plasmonics-enhanced and optically modulated delivery of gold nanostars into brain tumor.

    PubMed

    Yuan, Hsiangkuo; Wilson, Christy M; Xia, Jun; Doyle, Sarah L; Li, Shuqin; Fales, Andrew M; Liu, Yang; Ozaki, Ema; Mulfaul, Kelly; Hanna, Gabi; Palmer, Gregory M; Wang, Lihong V; Grant, Gerald A; Vo-Dinh, Tuan

    2014-04-21

    Plasmonics-active gold nanostars exhibiting strong imaging contrast and efficient photothermal transduction were synthesized for a novel pulsed laser-modulated plasmonics-enhanced brain tumor microvascular permeabilization. We demonstrate a selective, optically modulated delivery of nanoprobes into the tumor parenchyma with minimal off-target distribution.

  8. Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain metastasis.

    PubMed

    Zhang, Yong; Miwa, Shinji; Zhang, Nan; Hoffman, Robert M; Zhao, Ming

    2015-02-20

    Brain metastasis is a morbid, treatment-resistant, end-stage frequent occurrence in breast cancer patients. The aim of this study was to evaluate the efficacy of tumor-targeting Salmonella typhimurium A1-R on breast cancer brain metastases. High brain-metastatic variants of murine 4T1 breast cancer cells expressing red fluorescent protein (RFP) were injected orthotopically in the mammary fat pad in non-transgenic nude mice or in the left ventricle of non-transgenic nude mice and transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP). ND-GFP mice express GFP in nascent blood vessels. In the orthotopically-injected mice, the primary tumor was surgically-resected in order to allow brain metastasis to develop. At various time points, the tumors and vasculature in the brain were imaged by confocal and stereo fluorescence microscopy. Some of the breast cancer cells that reached the brain extravasated and grew perivascularly and some of the cells proliferated within the vasculature. S. typhimurium A1-R significantly inhibited brain metastasis in both metastatic models and increased survival of the orthotopically-transplanted, primary-tumor-resected mice (p<0.05). The results of the present study suggest the clinical potential of bacterial therapy of breast cancer brain metastasis.

  9. The Relationship between Parkinson Disease and Brain Tumor: A Meta-Analysis

    PubMed Central

    Ye, Rong; Shen, Ting; Jiang, Yasi; Xu, Lingjia; Si, Xiaoli; Zhang, Baorong

    2016-01-01

    Objective Epidemiological studies have investigated the association between Parkinson disease (PD) occurrence and the risk of brain tumors, while the results remain controversial. We performed a meta-analysis to clarify the exact relationship between PD and brain tumors. Methods A systematic literature search was conducted using PubMed, Embase, ScienceDirect and CBM (China Biology Medicine Disc) before February 2016. Eligible studies were those that reported risk estimates of brain tumors among patients with PD or vice versa. A random-effects model was used to calculate the pooled odds ratio (OR) of the outcomes. Subgroup analyses and sensitivity analysis were conducted to explore the potential sources of heterogeneity. Results In total, eight studies involving 329,276 participants met our inclusion criteria. The pooled OR was 1.51 (95%CI 1.21–1.89), indicating that PD carried a higher risk of brain tumor. Analyses by temporal relationship found that the occurrence of brain tumor was significantly higher after the diagnosis of PD (OR 1.55, 95% CI 1.18–2.05), but not statistically significant before PD diagnosis (OR 1.21, 95%CI 0.93–1.58). Subgroup analysis showed that gender differences, ethnicity differences and the characteristic of the tumor (benign or malignant) did not make much change in the association between brain tumor and PD. Conclusions Our meta-analysis collecting epidemiological studies suggested a positive association of PD with brain tumors, while the influence of anti-parkinson drugs and ascertainment bias could not be excluded. Further studies with larger sample size and more strict inclusion criteria should be conducted in the future. PMID:27764145

  10. Location of brain tumor intersecting white matter tracts predicts patient prognosis.

    PubMed

    Mickevicius, Nikolai J; Carle, Alexander B; Bluemel, Trevor; Santarriaga, Stephanie; Schloemer, Fallon; Shumate, Derrick; Connelly, Jennifer; Schmainda, Kathleen M; LaViolette, Peter S

    2015-11-01

    Brain tumor cells invade adjacent normal brain along white matter (WM) bundles of axons. We therefore hypothesized that the location of tumor intersecting WM tracts would be associated with differing survival. This study introduces a method, voxel-wise survival analysis (VSA), to determine the relationship between the location of brain tumor intersecting WM tracts and patient prognosis. 113 primary glioblastoma (GBM) patients were retrospectively analyzed for this study. Patient specific tumor location, defined by contrast-enhancement, was combined with diffusion tensor imaging derived tractography to determine the location of axons intersecting tumor enhancement (AXITEs). VSA was then used to determine the relationship between the AXITE location and patient survival. Tumors intersecting the right anterior thalamic radiation (ATR), right inferior fronto-occipital fasciculus (IFOF), right and left cortico-spinal tract (CST), and corpus callosum (CC) were associated with decreased overall survival. Tumors intersecting the CST, body of the CC, right ATR, posterior IFOF, and inferior longitudinal fasciculus are associated with decreased progression-free survival (PFS), while tumors intersecting the right genu of the CC and anterior IFOF are associated with increased PFS. Patients with tumors intersecting the ATR, IFOF, CST, or CC had significantly improved survival prognosis if they were additionally treated with bevacizumab. This study demonstrates the usefulness of VSA by locating AXITEs associated with poor prognosis in GBM patients. This information should be included in patient-physician conversations, therapeutic strategy, and clinical trial design.

  11. Location of brain tumor intersecting white matter tracts predicts patient prognosis.

    PubMed

    Mickevicius, Nikolai J; Carle, Alexander B; Bluemel, Trevor; Santarriaga, Stephanie; Schloemer, Fallon; Shumate, Derrick; Connelly, Jennifer; Schmainda, Kathleen M; LaViolette, Peter S

    2015-11-01

    Brain tumor cells invade adjacent normal brain along white matter (WM) bundles of axons. We therefore hypothesized that the location of tumor intersecting WM tracts would be associated with differing survival. This study introduces a method, voxel-wise survival analysis (VSA), to determine the relationship between the location of brain tumor intersecting WM tracts and patient prognosis. 113 primary glioblastoma (GBM) patients were retrospectively analyzed for this study. Patient specific tumor location, defined by contrast-enhancement, was combined with diffusion tensor imaging derived tractography to determine the location of axons intersecting tumor enhancement (AXITEs). VSA was then used to determine the relationship between the AXITE location and patient survival. Tumors intersecting the right anterior thalamic radiation (ATR), right inferior fronto-occipital fasciculus (IFOF), right and left cortico-spinal tract (CST), and corpus callosum (CC) were associated with decreased overall survival. Tumors intersecting the CST, body of the CC, right ATR, posterior IFOF, and inferior longitudinal fasciculus are associated with decreased progression-free survival (PFS), while tumors intersecting the right genu of the CC and anterior IFOF are associated with increased PFS. Patients with tumors intersecting the ATR, IFOF, CST, or CC had significantly improved survival prognosis if they were additionally treated with bevacizumab. This study demonstrates the usefulness of VSA by locating AXITEs associated with poor prognosis in GBM patients. This information should be included in patient-physician conversations, therapeutic strategy, and clinical trial design. PMID:26376654

  12. Management of childhood brain tumors: consensus report by the Pediatric Hematology Oncology (PHO) Chapter of Indian Academy of Pediatrics (IAP).

    PubMed

    Bhat, Sunil; Yadav, Satya Prakash; Suri, Vaishali; Patir, Rana; Kurkure, Purna; Kellie, Stewart; Sachdeva, Anupam

    2011-12-01

    Brain tumors are the second most common childhood tumors and remain the leading cause of cancer related deaths in children. Appropriate diagnosis and management of these tumors are essential to improve survival. There are no clinical practical guidelines available for the management of brain tumors in India. This document is a consensus report prepared after a National Consultation on Pediatric Brain Tumors held in Delhi on 06 Nov 2008. The meeting was attended by eminent experts from all over the country, in the fields of Neurosurgery, Radiation Oncology, Pediatric Oncology, Neuropathology, Diagnostic Imaging, Pediatric Endocrinology and Allied Health Professionals. This article highlights that physicians looking after children with brain tumors should work as part of a multidisciplinary team to improve the survival, quality of life, neuro-cognitive outcomes and standards of care for children with brain tumors. Recommendations for when to suspect, diagnostic workup, initial management, long-term follow up and specific management of individual tumors are outlined.

  13. 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

  14. 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

  15. Recent patents on imaging nanoprobes for brain tumor diagnosis and therapy.

    PubMed

    Qi, Lifeng; Zheng, Shu; Lin, Biaoyang

    2010-06-01

    Multifunctional nanoprobes, such as nanocrystals, nanoshells, and luminescent nanomaterials, have been developed for imaging biological processes; such as cell signaling, neuroimaging, protein conformation probing, DNA conformation probing, gene transcription, virus infection and replication in cells, protein dynamics, tumor diagnosis, and therapy evaluation. With the application of nanotechnology for CNS-active agents' delivery, nanostructured materials are emerging as a powerful means for diagnosis of CNS disorders, including brain tumors, because of their unique optical size, and surface properties. This review summarizes the recent patents on imaging nanoprobes for brain tumor diagnosis and therapy. The future development in this active cross-disciplinary field will be discussed as well. PMID:20156135

  16. Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

    PubMed Central

    Wang, Yuxuan; Springer, Simeon; Zhang, Ming; McMahon, K. Wyatt; Kinde, Isaac; Dobbyn, Lisa; Ptak, Janine; Brem, Henry; Chaichana, Kaisorn; Gallia, Gary L.; Gokaslan, Ziya L.; Groves, Mari L.; Jallo, George I.; Lim, Michael; Olivi, Alessandro; Quinones-Hinojosa, Alfredo; Rigamonti, Daniele; Riggins, Greg J.; Sciubba, Daniel M.; Weingart, Jon D.; Wolinsky, Jean-Paul; Ye, Xiaobu; Oba-Shinjo, Sueli Mieko; Marie, Suely K. N.; Holdhoff, Matthias; Agrawal, Nishant; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Bettegowda, Chetan

    2015-01-01

    Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57–88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88–100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher’s exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord. PMID:26195750

  17. Childhood Brain Tumors, Residential Insecticide Exposure, and Pesticide Metabolism Genes

    PubMed Central

    Nielsen, Susan Searles; McKean-Cowdin, Roberta; Farin, Federico M.; Holly, Elizabeth A.; Preston-Martin, Susan; Mueller, Beth A.

    2010-01-01

    Background Insecticides that target the nervous system may play a role in the development of childhood brain tumors (CBTs). Constitutive genetic variation affects metabolism of these chemicals. Methods We analyzed population-based case–control data to examine whether CBT is associated with the functional genetic polymorphisms PON1C–108T, PON1Q192R, PON1L55M, BCHEA539T, FMO1C–9536A, FMO3E158K, ALDH3A1S134A, and GSTT1 (null). DNA was obtained from newborn screening archives for 201 cases and 285 controls, ≤ 10 years of age, and born in California or Washington State between 1978 and 1990. Conception-to-diagnosis home insecticide treatment history was ascertained by interview. Results We observed no biologically plausible main effects for any of the metabolic polymorphisms with CBT risk. However, we observed strong interactions between genotype and insecticide exposure during childhood. Among exposed children, CBT risk increased per PON1–108T allele [odds ratio (OR) = 1.8; 95% confidence interval (CI), 1.1–3.0] and FMO1–9536A (*6) allele (OR = 2.7; 95% CI, 1.2–5.9), whereas among children never exposed, CBT risk was not increased (PON1: OR = 0.7; 95% CI, 0.5–1.0, interaction p = 0.005; FMO1: OR = 1.0; 95% CI, 0.6–1.6, interaction p = 0.009). We observed a similar but statistically nonsignificant interaction between childhood exposure and BCHEA539T (interaction p = 0.08). These interactions were present among both Hispanic and non-Hispanic white children. Conclusion Based on known effects of these variants, these results suggest that exposure in childhood to organophosphorus and perhaps to carbamate insecticides in combination with a reduced ability to detoxify them may be associated with CBT. Confirmation in other studies is required. PMID:20056567

  18. Support after Brain Tumor Means Different Things: Family Caregivers’ Experiences of Support and Relationship Changes

    PubMed Central

    Ownsworth, Tamara; Goadby, Elizabeth; Chambers, Suzanne Kathleen

    2015-01-01

    Shorter hospital stays and greater emphasis on outpatient care means that family members have the primary responsibility for supporting a person with brain tumor to manage the physical, cognitive, behavioral, and emotional effects of the illness and its treatment. Given the integral role of family caregivers, it is essential to understand their experience of the impact of brain tumor and their own support needs. Accordingly, this qualitative study aimed to investigate family caregivers’ experiences of support and relationship changes in the context of brain tumor. In-depth interviews were conducted with 11 family caregivers (8 spouse/partner, 3 parents) of people with malignant or benign tumor. A thematic analysis of interview transcripts identified two major themes, namely, “Meanings of Support” and “Relationship Impacts.” The Meanings of Support theme was characterized by intertwined and distinct support needs, varied expectations of support and factors influencing support expectations. The Relationship Impacts theme depicted mixed experiences of strengthened, maintained, and strained relations with the person with brain tumor. Overall, the findings highlight that there is considerable variability in caregivers’ experiences and expectations of support and the impact of brain tumor on relationships. The implications of these findings for the provision of caregiver support are discussed. PMID:25729740

  19. Rapid, label-free detection of brain tumors with stimulated Raman scattering microscopy

    PubMed Central

    Ji, Minbiao; Orringer, Daniel A.; Freudiger, Christian W.; Ramkissoon, Shakti; Liu, Xiaohui; Lau, Darryl; Golby, Alexandra J.; Norton, Isaiah; Hayashi, Marika; Agar, Nathalie Y.R.; Young, Geoffrey S.; Spino, Cathie; Santagata, Sandro; Camelo-Piragua, Sandra; Ligon, Keith L.; Sagher, Oren; Xie, X. Sunney

    2013-01-01

    Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. Here we describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from non-neoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and H&E microscopy for detection of glioma infiltration (κ=0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct. PMID:24005159

  20. Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

    SciTech Connect

    Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

    2013-03-01

    Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to

  1. Neuroimaging of pediatric brain tumors: from basic to advanced magnetic resonance imaging (MRI).

    PubMed

    Panigrahy, Ashok; Blüml, Stefan

    2009-11-01

    In this review, the basic magnetic resonance concepts used in the imaging approach of a pediatric brain tumor are described with respect to different factors including understanding the significance of the patient's age. Also discussed are other factors directly related to the magnetic resonance scan itself including evaluating the location of the tumor, determining if the lesion is extra-axial or intra-axial, and evaluating the contrast characteristics of the lesion. Of note, there are key imaging features of pediatric brain tumors, which can give information about the cellularity of the lesion, which can then be confirmed with advanced magnetic resonance imaging (MRI) techniques. The second part of this review will provide an overview of the major advanced MRI techniques used in pediatric imaging, particularly, magnetic resonance diffusion, magnetic resonance spectroscopy, and magnetic resonance perfusion. The last part of the review will provide more specific information about the use of advanced magnetic resonance techniques in the evaluation of pediatric brain tumors.

  2. Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: application to brain tumors.

    PubMed

    Miladi, Imen; Duc, Géraldine Le; Kryza, David; Berniard, Aurélie; Mowat, Pierre; Roux, Stéphane; Taleb, Jacqueline; Bonazza, Pauline; Perriat, Pascal; Lux, François; Tillement, Olivier; Billotey, Claire; Janier, Marc

    2013-09-01

    Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood-brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

  3. Quantitative analysis of topoisomerase IIalpha to rapidly evaluate cell proliferation in brain tumors.

    PubMed

    Oda, Masashi; Arakawa, Yoshiki; Kano, Hideyuki; Kawabata, Yasuhiro; Katsuki, Takahisa; Shirahata, Mitsuaki; Ono, Makoto; Yamana, Norikazu; Hashimoto, Nobuo; Takahashi, Jun A

    2005-06-17

    Immunohistochemical cell proliferation analyses have come into wide use for evaluation of tumor malignancy. Topoisomerase IIalpha (topo IIalpha), an essential nuclear enzyme, has been known to have cell cycle coupled expression. We here show the usefulness of quantitative analysis of topo IIalpha mRNA to rapidly evaluate cell proliferation in brain tumors. A protocol to quantify topo IIalpha mRNA was developed with a real-time RT-PCR. It took only 3 h to quantify from a specimen. A total of 28 brain tumors were analyzed, and the level of topo IIalpha mRNA was significantly correlated with its immuno-staining index (p<0.0001, r=0.9077). Furthermore, it sharply detected that topo IIalpha mRNA decreased in growth-inhibited glioma cell. These results support that topo IIalpha mRNA may be a good and rapid indicator to evaluate cell proliferate potential in brain tumors.

  4. Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response.

    PubMed

    Moffat, Bradford A; Chenevert, Thomas L; Lawrence, Theodore S; Meyer, Charles R; Johnson, Timothy D; Dong, Qian; Tsien, Christina; Mukherji, Suresh; Quint, Douglas J; Gebarski, Stephen S; Robertson, Patricia L; Junck, Larry R; Rehemtulla, Alnawaz; Ross, Brian D

    2005-04-12

    Assessment of radiation and chemotherapy efficacy for brain cancer patients is traditionally accomplished by measuring changes in tumor size several months after therapy has been administered. The ability to use noninvasive imaging during the early stages of fractionated therapy to determine whether a particular treatment will be effective would provide an opportunity to optimize individual patient management and avoid unnecessary systemic toxicity, expense, and treatment delays. We investigated whether changes in the Brownian motion of water within tumor tissue as quantified by using diffusion MRI could be used as a biomarker for early prediction of treatment response in brain cancer patients. Twenty brain tumor patients were examined by standard and diffusion MRI before initiation of treatment. Additional images were acquired 3 weeks after initiation of chemo- and/or radiotherapy. Images were coregistered to pretreatment scans, and changes in tumor water diffusion values were calculated and displayed as a functional diffusion map (fDM) for correlation with clinical response. Of the 20 patients imaged during the course of therapy, 6 were classified as having a partial response, 6 as stable disease, and 8 as progressive disease. The fDMs were found to predict patient response at 3 weeks from the start of treatment, revealing that early changes in tumor diffusion values could be used as a prognostic indicator of subsequent volumetric tumor response. Overall, fDM analysis provided an early biomarker for predicting treatment response in brain tumor patients. PMID:15805192

  5. Differentiating histologic malignancy of primary brain tumors: Pentavalent Technetium-99m-DMSA

    SciTech Connect

    Hirano, Tsuneo; Otake, Hidenori; Shibasaki, Takashi

    1997-01-01

    This study assessed pentavalent {sup 99m}Tc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy. SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq {sup 99m}Tc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. Approximately 95% of both benign and malignant primary brain tumors were demonstrated by {sup 99m}Tc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. 16 refs., 6 figs., 2 tabs.

  6. The effects of treatment for posterior fossa brain tumors on selective attention.

    PubMed

    Mabbott, Donald J; Snyder, Janice J; Penkman, Louise; Witol, Adrienne

    2009-03-01

    We sought to identify whether deficits in selective attention are present in pediatric brain tumor patients. Selective attention was assessed with covert-orienting, filtering, and visual-search tasks in 54 patients with either (1) posterior fossa (PF) tumors treated with cranial radiation and surgery (n = 22); (2) PF tumors treated with surgery alone (n = 17); or (3) non-CNS tumors (n = 15), who served as a patient control group. To account for normal development, patient performance was also compared with that of healthy age-matched controls (n = 10). We found that in PF tumor patients selective attention was impaired, regardless of whether they were treated with cranial radiation and surgery or surgery alone. However, patients treated with cranial radiation were most impaired. These patients may have greater damage to posterior brain regions know to mediate selective attention as the result of tumor location, effects of surgery, and higher doses of radiation to the posterior regions of the brain. These findings help to elucidate the potential impact of pediatric brain tumors and their treatment on discrete attentional skills.

  7. Yes-associated protein 1 is widely expressed in human brain tumors and promotes glioblastoma growth.

    PubMed

    Orr, Brent A; Bai, Haibo; Odia, Yazmin; Jain, Deepali; Anders, Robert A; Eberhart, Charles G

    2011-07-01

    The hippo pathway and its downstream mediator yes-associated protein 1 (YAP1) regulate mammalian organ size in part through modulating progenitor cell numbers. YAP1 has also been implicated as an oncogene in multiple human cancers. Currently, little is known about the expression of YAP1 either in normal human brain tissue or in central nervous system neoplasms. We used immunohistochemistry to evaluate nuclear YAP1 expression in the fetal and normal adult human brains and in 264 brain tumors. YAP1 was expressed in fetal and adult brain regions known to harbor neural progenitor cells, but there was little YAP1 immunoreactivity in the adult cerebral cortex. YAP1 protein was also readily detected in the nuclei of human brain tumors. In medulloblastoma, the expression varied between histologic subtypes and was most prominent in nodular/desmoplastic tumors. In gliomas, it was frequently expressed in infiltrating astrocytomas and oligodendrogliomas but rarely in pilocytic astrocytomas. Using a loss-of-function approach, we show that YAP1 promoted growth of glioblastoma cell lines in vitro. High levels of YAP1 messenger RNA expression were associated with aggressive molecular subsets of glioblastoma and with a nonsignificant trend toward reduced mean survival in human astrocytoma patients. These findings suggest that YAP1 may play an important role in normal human brain development and that it could represent a new target in human brain tumors.

  8. Prognostic Role of microRNA-21 Expression in Brain Tumors: a Meta-analysis.

    PubMed

    He, Xiao-Yan; Liao, Yu-Dong; Guo, Xiao-Qing; Wang, Robin; Xiao, Zhen-Yu; Wang, Yan-Gang

    2016-04-01

    Many studies have shown that microRNAs have important roles in the development and progression of various cancers. Recent studies also showed that microRNA-21 expression may be associated with the prognosis of patients with several common cancers. However, there was still lack of evidence for the prognostic role of microRNA-21 expression in brain tumors. We performed a systemic review and meta-analysis of published and unpublished studies to assess the prognostic role of microRNA-21 expression in patients with brain tumors. PubMed, Embase, and Google Scholar databases were searched for eligible studies with data assessing the prognostic role of microRNA-21 expression in brain tumors. Pooled hazard ratios (HRs) of microRNA-21 expression for overall survival and 95% confidence intervals (CI) were calculated. Six studies from five publications were finally included into the meta-analysis. Those six studies included a total of 747 patients with brain tumors and 654 patients with gliomas. For overall survival, the pooled HR of higher microRNA-21 expression in patients with brain tumors was 1.82 (95% CI 1.29-2.58, P = 0.001). In patients with gliomas, the HR for overall survival of higher microRNA-21 expression was 1.83 (95% CI 1.09-3.09, P = 0.023). Sensitivity analysis by omitting one study by turns also showed there was no obvious influence of individual study on the pooled HRs. There was no obvious risk of publication bias in the meta-analysis. The present meta-analysis suggests that microRNA-21 is associated with the prognosis of patients with brain tumors, and high expression of microRNA-21 can predict poor prognosis in patients with brain tumors.

  9. Pediatric Cancers and Brain Tumors in Adolescents and Young Adults.

    PubMed

    McCabe, Martin G; Valteau-Couanet, Dominique

    2016-01-01

    Embryonal tumors classically occur in young children, some principally within the first year of life. Prospective national and international clinical trials during recent decades have brought about progressive improvements in survival, and associated biological studies have advanced our understanding of tumor biology, in some cases allowing biological tumor characteristics to be harnessed for therapeutic benefit. Embryonal tumors continue to occur, albeit less commonly, during childhood, adolescence and throughout adulthood. These tumors are less well understood, usually not managed according to standardized protocols and rarely included in clinical trials. Survival outcomes are generally poorer than their childhood equivalents. We present here a summary of the published literature on embryonal tumors that present ectopically during adolescence and adulthood. We show that for some tumors protocol-driven treatment, supported by accurate and complete diagnostics and staging, can result in equivalent outcomes to those seen during childhood. We make the case that clinical trial eligibility criteria should be disease-based rather than age-based, and support improvements in dialogue between children's and adults' cancer clinicians to improve outcomes for these rare tumors. PMID:27595358

  10. Gonadal status in male survivors following childhood brain tumors.

    PubMed

    Schmiegelow, M; Lassen, S; Poulsen, H S; Schmiegelow, K; Hertz, H; Andersson, A M; Skakkebaek, N E; Müller, J

    2001-06-01

    The effect of radiotherapy (RT) and chemotherapy (CT) on gonadal function was assessed in males treated for a childhood brain tumor not directly involving the hypothalamus/pituitary (HP) axis in a population-based study with a long follow-up time. All males <15 yr at the time of diagnosis (median: 9.0 yr, range: 0.8 to 14.9 yr) and diagnosed from January 1970 through February 1997 in the eastern part of Denmark and [gte]18 yr at the time of follow-up (median: 25.8 yr, range:18.5 to 39.3 yr) were included. Thirty males fulfilled the criteria. The median age at time of RT was 9.0 yr (range: 0.8 to 14.9 yr) and the median length of follow-up was 18 yr (range: 2.0 to 28.0 yr). The biological effective dose of RT was determined to the HP region and to the spine and expressed in gray because the biological effective dose gives a means of expressing the biological effect on normal tissue of different dosage schedules in a uniform way. Levels of serum FSH, luteinizing hormone (LH), sexual hormone-binding globulin, testosterone, and inhibin B were measured and compared with healthy age-matched male controls (n = 347), and the patients had a GnRH stimulation test performed with determination of peak FSH and LH. Patients treated with RT + CT (n = 13), compared with patients treated with RT only (n = 17), had significantly higher median peak FSH (8.33 vs. 3.79 IU/L, P = 0.03) and median peak LH (20.0 vs. 12.8 IU/L, P = 0.03), and significantly lower median inhibin B (86.0 vs. 270 pg/ml, P = 0.03), and median inhibin B/FSH ratio (12.8 vs. 107.9, P = 0.04), which indicates gonadal damage. Inhibin B and inhibin B/FSH ratio were also significantly lower in the RT + CT group, compared with controls (median: 86.0 vs. 215 pg/ml, P = 0.02), (median:12.8 vs. 67; P = 0.01), respectively. We found a significantly inverse correlation between basal FSH and inhibin B and FSH and total testicular volume (r(s) = -0.83; P < 0.0001), (r(s) = -0.67; P < 0.0001), respectively, and a significant

  11. Novel polyomavirus associated with brain tumors in free-ranging raccoons, western United States.

    PubMed

    Dela Cruz, Florante N; Giannitti, Federico; Li, Linlin; Woods, Leslie W; Del Valle, Luis; Delwart, Eric; Pesavento, Patricia A

    2013-01-01

    Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in 10 raccoons during March 2010-May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons.

  12. MEG localization of spike sources in human patients with brain tumors.

    PubMed

    Birbilis, T; Anninos, P; Seimenis, I; Adamopoulos, A; Kotini, A

    2014-09-01

    The purpose of this study was to use magnetoencephalography (MEG) to identify epileptic zones in patients with brain tumors before undergoing tumor surgery. The MEG data were recorded with a 122-channel biomagnetometer. Equivalent current dipoles (ECD) were calculated for epileptic spikes on MEG recordings according to the single dipole model. Eight patients (five males and three females) within the age range (43-73 years; mean ± SD = 55.12 ± 9.77) were examined by MEG before neurosurgery operation. Four patients had meningioma grade I, three had glioblastoma grade IV and one had astrocytoma grade II. All the patients showed ECD at their MEG's before surgical operation except a female one with meningioma who showed no ECD. Tumors observed in the frontal areas show posteriorly located ECD. We conclude that the MEG is a valuable clinical tool for the localization of epileptic foci in patients with brain tumors before surgical tumor operation.

  13. Novel Polyomavirus associated with Brain Tumors in Free-Ranging Raccoons, Western United States

    PubMed Central

    Dela Cruz, Florante N.; Giannitti, Federico; Li, Linlin; Woods, Leslie W.; Del Valle, Luis; Delwart, Eric

    2013-01-01

    Tumors of any type are exceedingly rare in raccoons. High-grade brain tumors, consistently located in the frontal lobes and olfactory tracts, were detected in 10 raccoons during March 2010–May 2012 in California and Oregon, suggesting an emerging, infectious origin. We have identified a candidate etiologic agent, dubbed raccoon polyomavirus, that was present in the tumor tissue of all affected animals but not in tissues from 20 unaffected animals. Southern blot hybridization and rolling circle amplification showed the episomal viral genome in the tumors. The multifunctional nuclear protein large T-antigen was detectable by immunohistochemical analyses in a subset of neoplastic cells. Raccoon polyomavirus may contribute to the development of malignant brain tumors of raccoons. PMID:23260029

  14. 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

  15. Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: Crossing the blood-brain-barrier divide

    PubMed Central

    Chacko, Ann-Marie; Li, Chunsheng; Pryma, Daniel A.; Brem, Steven; Coukos, George; Muzykantov, Vladimir R.

    2014-01-01

    Introduction Brain tumors are inherently difficult to treat in large part due to the cellular blood-brain barriers (BBB) that limit the delivery of therapeutics to the tumor tissue from the systemic circulation. Virtually no large-molecules, including antibody-based proteins, can penetrate the BBB. With antibodies fast becoming attractive ligands for highly specific molecular targeting to tumor antigens, a variety of methods are being investigated to enhance the access of these agents to intracranial tumors for imaging or therapeutic applications. Areas covered This review describes the characteristics of the BBB and the vasculature in brain tumors, described as the blood-brain tumor barrier (BBTB). Antibodies targeted to molecular markers of CNS tumors will be highlighted, and current strategies for enhancing the delivery of antibodies across these cellular barriers into the brain parenchyma to the tumor will be discussed. Non-invasive imaging approaches to assess BBB/BBTB permeability and/or antibody targeting will be presented as a means of guiding the optimal delivery of targeted agents to brain tumors. Expert Opinion Pre-clinical and clinical studies highlight the potential of several approaches in increasing brain tumor delivery across the blood-brain barrier divide. However, each carries its own risks and challenges. There is tremendous potential in using neuroimaging strategies to assist in understanding and defining the challenges to translating and optimizing molecularly-targeted antibody delivery to CNS tumors to improve clinical outcomes. PMID:23751126

  16. Detection of an atypical teratoid rhabdoid brain tumor gene deletion in circulating blood using next-generation sequencing.

    PubMed

    Chakravadhanula, Madhavi; Tembe, Waibhav; Legendre, Christophe; Carpentieri, David; Liang, Winnie S; Bussey, Kimberly J; Carpten, John; Berens, Michael E; Bhardwaj, Ratan D

    2014-09-01

    Circulating biomarkers such as somatic chromosome mutations are novel diagnostic tools to detect cancer noninvasively. We describe focal deletions found in a patient with atypical teratoid rhabdoid tumor, a highly aggressive early childhood pediatric tumor. First, we used magnetic resonance imaging (MRI) and histopathology to study the tumor anatomy. Next, we used whole genome sequencing (Next Gen Sequencing) and Bioinformatics interrogation to discover the presence of 3 focal deletions in tumor tissue and 2 of these 3 focal deletions in patient's blood also. About 20% of the blood DNA sequencing reads matched the tumor DNA reads at the SMARCB1 gene locus. Circulating, tumor-specific DNA aberrations are a promising biomarker for atypical teratoid rhabdoid tumor patients. The high percentage of tumor DNA detected in blood indicates that either circulating brain tumor cells lyse in the blood or that contents of brain tumor cells traverse a possibly compromised blood-brain barrier in this patient.

  17. Beauty product-related exposures and childhood brain tumors in seven countries: results from the SEARCH International Brain Tumor Study.

    PubMed

    Efird, J T; Holly, E A; Cordier, S; Mueller, B A; Lubin, F; Filippini, G; Peris-Bonet, R; McCredie, M; Arslan, A; Bracci, P; Preston-Martin, S

    2005-04-01

    Data from 1218 cases of childhood brain tumors (CBT) diagnosed between 1976 and 1994 and 2223 matched controls from the general population were included in an analysis of maternal beauty product exposure and beauty-related employment in 9 centers in 7 countries. A 50% increased odds ratio (OR) [95% confidence interval (CI) = 1.0-2.1] for CBT was observed among children of mothers who were exposed via personal use of and/or possible ambient contact with beauty products during the 5 years preceding the index child's birth compared with children of mothers never exposed to beauty products during this time period. Overall maternal personal use of hair-coloring agents in the month before or during the pregnancy of the index child's birth was not associated with CBT (OR = 1.0, CI = 0.83-1.3) or with astroglial (OR = 1.1, CI = 0.85-1.4), PNET (OR = 1.0, CI = 0.71-1.5) and other glial subtypes (OR = 1.0, CI = 0.62-1.0). Similarly, no statistically increased ORs or discernable pattern of risk estimates were observed for period of use or for number of applications per year for maternal personal use of hair-coloring agents overall or by histologic type. Among children born on or after 1980, increased ORs for CBT were associated with maternal non-work-related exposure to any beauty products (OR = 2.6, CI = 1.2-5.9), hair-dyes (OR = 11, CI = 1.2-90), and hair sprays (OR = 3.4, CI = 1.0-11). No overall increased OR for CBT was observed among children of mothers employed in beauty-related jobs during the 5 years preceding the index child's birth compared with those who reported no beauty-related employment. In general, other specific beauty product-related exposures were not associated with increased ORs for CBT. Data from our study provide little evidence of an increased risk for CBT with mothers' exposures to beauty products.

  18. Levetiracetam for seizure prevention in brain tumor patients: a systematic review.

    PubMed

    Nasr, Ziad Ghantous; Paravattil, Bridget; Wilby, Kyle John

    2016-08-01

    Seizures are common complications for patients with brain tumors. No clear evidence exists regarding the use of antiepileptic agents for prophylactic use yet newer agents are being favoured in many clinical settings. The objective of this systematic review was to determine the efficacy of levetiracetam for preventing seizures in patients with brain tumors. A literature search was completed using the databases PubMed (1948 to December 2015), EMBASE (1980 to December 2015), Cochrane Database of Systematic Reviews, and Google Scholar. Studies were included if they reported seizure frequency data pertaining to levetiracetam use in patients with brain tumors as either monotherapy or as an add on agent. The literature search produced 21 articles (3 randomized controlled trials, seven prospective observational studies, and 11 retrospective observational studies). All studies were found to be at high risk of bias. Overall, studies show levetiracetam decreased seizure frequency in brain tumor patients with or without craniotomy. Safety outcomes were also favourable. As such, levetiracetam appears effective for reducing seizures in patients with brain tumors and may be considered a first-line agent. However, there is an urgent need for more high quality prospective data assessing levetiracetam and other antiepileptic drugs in this population. PMID:27168191

  19. Mobile Phones, Brain Tumors, and the Interphone Study: Where Are We Now?

    PubMed Central

    Feychting, Maria; Green, Adele C.; Kheifets, Leeka; Savitz, David A.

    2011-01-01

    Background: In the past 15 years, mobile telephone use has evolved from an uncommon activity to one with > 4.6 billion subscriptions worldwide. However, there is public concern about the possibility that mobile phones might cause cancer, especially brain tumors. Objectives: We reviewed the evidence on whether mobile phone use raises the risk of the main types of brain tumor—glioma and meningioma—with a particular focus on the recent publication of the largest epidemiologic study yet: the 13-country Interphone Study. Discussion: Methodological deficits limit the conclusions that can be drawn from the Interphone study, but its results, along with those from other epidemiologic, biological, and animal studies and brain tumor incidence trends, suggest that within about 10–15 years after first use of mobile phones there is unlikely to be a material increase in the risk of brain tumors in adults. Data for childhood tumors and for periods beyond 15 years are currently lacking. Conclusions: Although there remains some uncertainty, the trend in the accumulating evidence is increasingly against the hypothesis that mobile phone use can cause brain tumors in adults. PMID:22171384

  20. Epidemiology of primary brain tumors: current concepts and review of the literature.

    PubMed Central

    Wrensch, Margaret; Minn, Yuriko; Chew, Terri; Bondy, Melissa; Berger, Mitchel S.

    2002-01-01

    The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. PMID:12356358

  1. 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.

  2. Seizure Prognosis in Brain Tumors: New Insights and Evidence-Based Management

    PubMed Central

    Kerkhof, Melissa; Duran-Pena, Alberto

    2014-01-01

    Brain tumor-related epilepsy (BTE) is common in low- and high-grade gliomas. The risk of seizures varies between 60% and 100% among low-grade gliomas and between 40% and 60% in glioblastomas. The presence of seizures in patients with brain tumors implies favorable and unfavorable factors. New-onset seizures represent an early warning sign for the presence of a brain tumor and count as a good prognostic factor for survival. Recurrence or worsening of seizures during the course of disease may signal tumor progression. Each of the modalities for tumor control (i.e., surgery, radiotherapy, chemotherapy) contributes to seizure control. Nevertheless, one third of BTE shows pharmacoresistance to antiepileptic drugs (AEDs) and may severely impair the burden of living with a brain tumor. For symptomatic therapy of BTE, seizure type and individual patient factors determine the appropriate AED. Randomized controlled trials in partial epilepsy in adults to which type BTE belongs and additional studies in gliomas indicate that levetiracetam is the agent of choice, followed by valproic acid (VPA). In the case of recurring seizures, combining these two drugs (polytherapy) seems effective and possibly synergistic. If either one is not effective or not well tolerated, lacosamide, lamotrigine, or zonisamide are additional options. A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. A practice guideline on symptomatic medical management including dose schedules of AEDs is supplied. PMID:24899645

  3. Expression of β-adrenergic receptors in pediatric malignant brain tumors

    PubMed Central

    SARDI, IACOPO; GIUNTI, LAURA; BRESCI, CECILIA; BUCCOLIERO, ANNA MARIA; DEGL’INNOCENTI, DUCCIO; CARDELLICCHIO, STEFANIA; BARONI, GIANNA; CASTIGLIONE, FRANCESCA; ROS, MARTINA DA; FIORINI, PATRIZIO; GIGLIO, SABRINA; GENITORI, LORENZO; ARICÒ, MAURIZIO; FILIPPI, LUCA

    2013-01-01

    β-adrenergic receptors (β-ARs) are G protein-coupled receptors that activate signal transduction pathways involved in angiogenesis, resulting in enhanced tumor vascularization and more aggressive growth. In this study, we evaluated the expression of β-ARs in a population of 12 children affected by malignant primary brain tumors. We found a significant expression of β1- and β2-ARs in all 12 samples as well as the 3 cell lines tested (U87MG, T98G and DAOY). The mean absolute β1-AR mRNA level standardized to GAPDH was 5.81 (range, -7.91 to 11.29) for brain tumors and 8.59 (range, 6.046 to 12.59) for cell lines (U87MG, DAOY and T98G), respectively. The mean absolute β2-AR mRNA level was 4.74 (range, −9.30 to 8.45) for tumor specimens and 7.64 (range, 5.85 to 8.88) for cell lines. These real-time quantitative (qRT)-PCR expression data were confirmed by immunohistochemical analysis. Our study evaluated the presence of β1- and β2-ARs in malignant pediatric brain tumors and brain tumor cell lines. PMID:23255924

  4. Occupation, socioeconomic status, and brain tumor mortality: a death certificate-based case-control study.

    PubMed

    Demers, P A; Vaughan, T L; Schommer, R R

    1991-09-01

    The relationships between brain tumor mortality and occupation and socioeconomic status (SES) were evaluated in a death certificate-based case-control study. The cases consisted of 904 white men aged 20 years and older who died of a brain tumor in Washington state between 1969 and 1978. For each case a white male control of the same age was chosen. A consistent pattern of increasing risk with increasing SES was seen for all brain tumors as well as for gliomas and astrocytomas. After adjustment for SES, stationary engineers were found to be at excess risk across all histologies based on six cases vs no controls with lower 95% confidence intervals of 2.3 for all brain tumors, 2.8 for gliomas (based on three cases), and 2.1 for astrocytic tumors (based on two cases). Excesses of astrocytic tumors also were observed for petroleum refinery workers (OR = 8.8, CI = 2.2-35.2), forestry workers (OR = 8.5, CI = 1.1-63.4), and cleaning service workers (OR = 2.7, CI = 1.1-6.7).

  5. Targeting brain tumor cAMP: the case for sex-specific therapeutics

    PubMed Central

    Warrington, Nicole M.; Sun, Tao; Rubin, Joshua B.

    2015-01-01

    A relationship between cyclic adenosine 3′, 5′-monophosphate (cAMP) levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY) have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor) risk in individuals with Neurofibromatosis type 1 (NF1). Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well-known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex. PMID:26283963

  6. Enhanced transfection of brain tumor suppressor genes by photochemical internalization

    NASA Astrophysics Data System (ADS)

    Chou, Chih H.; Sun, Chung-Ho; Zhou, Yi-Hong; Madsen, Steen J.; Hirschberg, Henry

    2011-03-01

    One of many limitations for cancer gene therapy is the inability of the therapeutic gene to transfect a sufficient number of tumor cells. Photochemical internalization (PCI) is a photodynamic therapy-based approach for improving the delivery of macromolecules and genes into the cell cytosol. The utility of PCI for the delivery of a tumor suppressor gene (PAX-6) was investigated in monolayers and spheroids consisting of F98 rat glioma cells.

  7. Critical role of ABCG2 in ALA-photodynamic diagnosis and therapy of human brain tumor.

    PubMed

    Ishikawa, Toshihisa; Kajimoto, Yoshinaga; Inoue, Yutaka; Ikegami, Yoji; Kuroiwa, Toshihiko

    2015-01-01

    Primary brain tumors occur in around 250,000 people per year globally. Survival rates in primary brain tumors depend on the type of tumor, patient's age, the extent of surgical tumor removal, and other factors. Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma and meningiomas, whereas clinical application of photodynamic therapy (PDT) to brain tumor therapy has just recently started. Both PDD and PDT are achieved by a photon-induced physicochemical reaction, which is induced by the excitation of porphyrins exposed to light. In fluorescence-guided gross-total resection, PDD can be achieved by the administration of 5-aminolevulinic acid (5-ALA) as the precursor of protoporphyrin IX (PpIX). Exogenously administered ALA induces biosynthesis and accumulation of PpIX, a natural photosensitizer, in cancer cells. However, ATP-binding cassette transporter ABCG2 plays a critical role in regulating the cellular accumulation of porphyrins in cancer cells and thereby its expression and function can affect the efficacy of PDD and PDT. In response to the photoreaction of porphyrins leading to oxidative stress, the nuclear factor erythroid-derived 2-related transcription factor can transcriptionally upregulate ABCG2, which may reduce the efficacy of PDD and PDT. On the other hand, certain protein kinase inhibitors potentially enhance the efficacy of PDD and PDT by blocking ABCG2-mediated porphyrin efflux from cancer cells. In this context, it is of great interest to develop ABCG2 inhibitors that can be applied to PDD or PDT for the therapy of brain tumor and other tumors.

  8. What Are Brain and Spinal Cord Tumors in Children?

    MedlinePlus

    ... feet, and legs; problems with swallowing or synchronized eye movements; and changes in speech rhythm. Brain stem: The ... stiff muscles, or problems with sensation, facial or eye movement, hearing, or swallowing. Double vision is a common ...

  9. Human brain tumor xenografts in nude mice as a chemotherapy model.

    PubMed

    Houchens, D P; Ovejera, A A; Riblet, S M; Slagel, D E

    1983-06-01

    Two human brain tumors which were previously established in nude mice were used to determine antitumor efficacy of various therapeutic agents. These tumors were a medulloblastoma (TE-671) and a glioma (U-251) with mass doubling times of 3.5 and 5.5 days respectively as subcutaneous implants in nude mice. Intracranial (i.c.) tumor challenge was accomplished by inoculating tissue culture-grown cells of either tumor into the right cerebral hemisphere to a depth of 3 mm. Median survival time (MST) in untreated mice with 10(5) i.c. injected TE-671 cells was approximately 30 days and 53 days in the U-251 tumor. With 2 X 10(5) U-251 tumor cells the MST was 27-31 days. Groups of mice which had been inoculated with tumor were treated with various doses and schedules of antineoplastic compounds by the i.p. route. The TE-671 tumor responded to AZQ treatment with an increase in life span (ILS) of 37% compared to untreated controls and an ILS of 30% with CCNU treatment. BCNU and PCNU were ineffective. With the U-251 tumor BCNU produced an ILS of greater than 60%, with 75% cures, greater than 112% ILS with PCNU and 49% ILS with CCNU. Neither tumor responded to procarbazine, PALA, dianhydrogalactitol, D-O-norleucine or dibromodulcitol. The U-251 tumor was treated on various schedules and doses with BCNU and found to respond well on late as well as early treatment. A new drug (rapamycin) being investigated by the NCI was found to be very effective against the U-251 tumor. This model system should prove valuable in assessing the effects of various chemotherapeutic modalities against brain tumors.

  10. Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future.

    PubMed

    Mao, Xiao-Yuan; Dai, Jin-Xiang; Zhou, Hong-Hao; Liu, Zhao-Qian; Jin, Wei-Lin

    2016-05-31

    Although brain tumors have been known tremendously over the past decade, there are still many problems to be solved. The etiology of brain tumors is not well understood and the treatment remains modest. There is in great need to develop a suitable brain tumor models that faithfully mirror the etiology of human brain neoplasm and subsequently get more efficient therapeutic approaches for these disorders. In this review, we described the current status of animal models of brain tumors and analyzed their advantages and disadvantages. Additionally, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), a versatile genome editing technology for investigating the functions of target genes, and its application were also introduced in our present work. We firstly proposed that brain tumor modeling could be well established via CRISPR/Cas9 techniques. And CRISPR/Cas9-mediated brain tumor modeling was likely to be more suitable for figuring out the pathogenesis of brain tumors, as CRISPR/Cas9 platform was a simple and more efficient biological toolbox for implementing mutagenesis of oncogenes or tumor suppressors that were closely linked with brain tumors.

  11. Automated brain tumor segmentation using spatial accuracy-weighted hidden Markov Random Field.

    PubMed

    Nie, Jingxin; Xue, Zhong; Liu, Tianming; Young, Geoffrey S; Setayesh, Kian; Guo, Lei; Wong, Stephen T C

    2009-09-01

    A variety of algorithms have been proposed for brain tumor segmentation from multi-channel sequences, however, most of them require isotropic or pseudo-isotropic resolution of the MR images. Although co-registration and interpolation of low-resolution sequences, such as T2-weighted images, onto the space of the high-resolution image, such as T1-weighted image, can be performed prior to the segmentation, the results are usually limited by partial volume effects due to interpolation of low-resolution images. To improve the quality of tumor segmentation in clinical applications where low-resolution sequences are commonly used together with high-resolution images, we propose the algorithm based on Spatial accuracy-weighted Hidden Markov random field and Expectation maximization (SHE) approach for both automated tumor and enhanced-tumor segmentation. SHE incorporates the spatial interpolation accuracy of low-resolution images into the optimization procedure of the Hidden Markov Random Field (HMRF) to segment tumor using multi-channel MR images with different resolutions, e.g., high-resolution T1-weighted and low-resolution T2-weighted images. In experiments, we evaluated this algorithm using a set of simulated multi-channel brain MR images with known ground-truth tissue segmentation and also applied it to a dataset of MR images obtained during clinical trials of brain tumor chemotherapy. The results show that more accurate tumor segmentation results can be obtained by comparing with conventional multi-channel segmentation algorithms.

  12. Automated brain tumor segmentation using spatial accuracy-weighted hidden Markov Random Field.

    PubMed

    Nie, Jingxin; Xue, Zhong; Liu, Tianming; Young, Geoffrey S; Setayesh, Kian; Guo, Lei; Wong, Stephen T C

    2009-09-01

    A variety of algorithms have been proposed for brain tumor segmentation from multi-channel sequences, however, most of them require isotropic or pseudo-isotropic resolution of the MR images. Although co-registration and interpolation of low-resolution sequences, such as T2-weighted images, onto the space of the high-resolution image, such as T1-weighted image, can be performed prior to the segmentation, the results are usually limited by partial volume effects due to interpolation of low-resolution images. To improve the quality of tumor segmentation in clinical applications where low-resolution sequences are commonly used together with high-resolution images, we propose the algorithm based on Spatial accuracy-weighted Hidden Markov random field and Expectation maximization (SHE) approach for both automated tumor and enhanced-tumor segmentation. SHE incorporates the spatial interpolation accuracy of low-resolution images into the optimization procedure of the Hidden Markov Random Field (HMRF) to segment tumor using multi-channel MR images with different resolutions, e.g., high-resolution T1-weighted and low-resolution T2-weighted images. In experiments, we evaluated this algorithm using a set of simulated multi-channel brain MR images with known ground-truth tissue segmentation and also applied it to a dataset of MR images obtained during clinical trials of brain tumor chemotherapy. The results show that more accurate tumor segmentation results can be obtained by comparing with conventional multi-channel segmentation algorithms. PMID:19446435

  13. Ex vivo confocal microscopy imaging to identify tumor tissue on freshly removed brain sample.

    PubMed

    Forest, Fabien; Cinotti, Elisa; Yvorel, Violaine; Habougit, Cyril; Vassal, François; Nuti, Christophe; Perrot, Jean-Luc; Labeille, Bruno; Péoc'h, Michel

    2015-09-01

    Confocal microscopy is a technique able to realize "optic sections" of a tissue with increasing applications. We wondered if we could apply an ex vivo confocal microscope designed for dermatological purpose in a routine use for the most frequent brain tumors. The aim of this work was to identify tumor tissue and its histopathological hallmarks, and to assess grading criteria used in neuropathological practice without tissue loss on freshly removed brain tissue. Seven infiltrating gliomas, nine meningiomas and three metastases of carcinomas were included. We compared imaging results obtained with the confocal microscope to frozen sections, smears and tissue sections of formalin-fixed tissue. Our results show that ex vivo confocal microscopy imaging can be applied to brain tumors in order to quickly identify tumor tissue without tissue loss. It can differentiate tumors and can assess most of grading criteria. Confocal microscopy could represent a new tool to identify tumor tissue on freshly removed sample and could help in selecting areas for biobanking of tumor tissue.

  14. Perfusion MR Imaging: Clinical Utility for the Differential Diagnosis of Various Brain Tumors

    PubMed Central

    Cho, Sung Ki; Na, Dong Gyu; Ryoo, Jae Wook; Roh, Hong Gee; Moon, Chan Hong; Kim, Jong Hyun

    2002-01-01

    Objective To determine the utility of perfusion MR imaging in the differential diagnosis of brain tumors. Materials and Methods Fifty-seven patients with pathologically proven brain tumors (21 high-grade gliomas, 8 low-grade gliomas, 8 lymphomas, 6 hemangioblastomas, 7 metastases, and 7 various other tumors) were included in this study. Relative cerebral blood volume (rCBV) and time-to-peak (TTP) ratios were quantitatively analyzed and the rCBV grade of each tumor was also visually assessed on an rCBV map. Results The highest rCBV ratios were seen in hemangioblastomas, followed by high-grade gliomas, metastases, low-grade gliomas, and lymphomas. There was no significant difference in TTP ratios between each tumor group (p>0.05). At visual assessment, rCBV was high in 17 (81%) of 21 high-grade gliomas and in 4 (50%) of 8 low-grade gliomas. Hemangioblastomas showed the highest rCBV and lymphomas the lowest. Conclusion Perfusion MR imaging may be helpful in the differentiation of thevarious solid tumors found in the brain, and in assessing the grade of the various glial tumors occurring there. PMID:12271162

  15. Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors.

    PubMed

    Aizer, Ayal A; Du, Rose; Wen, Patrick Y; Arvold, Nils D

    2015-09-01

    Radiotherapy is often used in the management of primary brain tumors, but late cerebrovascular risks remain incompletely characterized. We examined the relationship between radiotherapy and the risk of death from cerebrovascular disease (CVD) in this population. We used the Surveillance, Epidemiology, and End Results Program to identify 19,565 patients of any age diagnosed with a primary brain tumor between 1983-2002. Multivariable competing risks analysis and an interaction model were used to determine whether receipt of radiotherapy was associated with an increased risk of CVD-specific death, adjusting for tumor proximity to central arterial circulations of the brain. The median follow up in surviving patients was 12.75 years. Baseline characteristics were similar in patients who did and did not receive radiotherapy. Ten-year CVD-specific mortality in patients with tumors near central arterial circulations who did and did not receive radiotherapy were 0.64 % (95 % CI 0.42-0.93 %) versus 0.16 % (95 % CI 0.055-0.40 %), p = 0.01. After adjustment for demographic, tumor-related, and treatment-related covariates, patients with tumors near central arterial circulations were significantly more likely to experience CVD-specific mortality after radiotherapy (HR 2.81; 95 % CI 1.25-6.31; p = 0.01); no association was observed among patients with more distant tumors (HR 0.77; 95 % CI 0.50-1.16; p = 0.21). The interaction model showed that tumor location was a key predictor of the risk of radiotherapy-associated, CVD-specific mortality (p-interaction = 0.004). Patients receiving radiotherapy for tumors near but not distant from the central vasculature of the brain are at increased risk for death secondary to CVD, which should be considered when counseling patients.

  16. Hybrid RGSA and Support Vector Machine Framework for Three-Dimensional Magnetic Resonance Brain Tumor Classification

    PubMed Central

    Rajesh Sharma, R.; Marikkannu, P.

    2015-01-01

    A novel hybrid approach for the identification of brain regions using magnetic resonance images accountable for brain tumor is presented in this paper. Classification of medical images is substantial in both clinical and research areas. Magnetic resonance imaging (MRI) modality outperforms towards diagnosing brain abnormalities like brain tumor, multiple sclerosis, hemorrhage, and many more. The primary objective of this work is to propose a three-dimensional (3D) novel brain tumor classification model using MRI images with both micro- and macroscale textures designed to differentiate the MRI of brain under two classes of lesion, benign and malignant. The design approach was initially preprocessed using 3D Gaussian filter. Based on VOI (volume of interest) of the image, features were extracted using 3D volumetric Square Centroid Lines Gray Level Distribution Method (SCLGM) along with 3D run length and cooccurrence matrix. The optimal features are selected using the proposed refined gravitational search algorithm (RGSA). Support vector machines, over backpropagation network, and k-nearest neighbor are used to evaluate the goodness of classifier approach. The preliminary evaluation of the system is performed using 320 real-time brain MRI images. The system is trained and tested by using a leave-one-case-out method. The performance of the classifier is tested using the receiver operating characteristic curve of 0.986 (±002). The experimental results demonstrate the systematic and efficient feature extraction and feature selection algorithm to the performance of state-of-the-art feature classification methods. PMID:26509188

  17. 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.

  18. Segmentation of brain tumors in 4D MR images using the hidden Markov model.

    PubMed

    Solomon, Jeffrey; Butman, John A; Sood, Arun

    2006-12-01

    Tumor size is an objective measure that is used to evaluate the effectiveness of anticancer agents. Responses to therapy are categorized as complete response, partial response, stable disease and progressive disease. Implicit in this scheme is the change in the tumor over time; however, most tumor segmentation algorithms do not use temporal information. Here we introduce an automated method using probabilistic reasoning over both space and time to segment brain tumors from 4D spatio-temporal MRI data. The 3D expectation-maximization method is extended using the hidden Markov model to infer tumor classification based on previous and subsequent segmentation results. Spatial coherence via a Markov Random Field was included in the 3D spatial model. Simulated images as well as patient images from three independent sources were used to validate this method. The sensitivity and specificity of tumor segmentation using this spatio-temporal model is improved over commonly used spatial or temporal models alone. PMID:17050032

  19. 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.

  20. Atlas to patient registration with brain tumor based on a mesh-free method.

    PubMed

    Diaz, Idanis; Boulanger, Pierre

    2015-08-01

    Brain atlas to patient registration in the presence of tumors is a challenging task because its presence cause brain structure deformations and introduce large intensity variation between the affected areas. This large dissimilarity affects the results of traditional registration methods based on intensity or shape similarities. In order to overcome these problems, we propose a novel method that brings closer the atlas and the patient's image by simulating the mechanical behavior of brain deformation under a tumor pressure. The proposed method use a mesh-free total Lagrangian Explicit Dynamic algorithm for the simulation of atlas deformation and a data driven model of the tumor using multi-modal MRI segmentation. Experimental results look structurally very similar to the patient's image and outperform two of the top ranking algorithms.

  1. 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.

  2. The long-term side effects of radiation therapy for benign brain tumors in adults.

    PubMed

    al-Mefty, O; Kersh, J E; Routh, A; Smith, R R

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors (two of these also had pituitary dysfunction). One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered "safe" treatment for benign brain tumors.

  3. The long-term side effects of radiation therapy for benign brain tumors in adults

    SciTech Connect

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. )

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  4. 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.

  5. Assessing Region of Interest Schemes for the Corticospinal Tract in Patients With Brain Tumors.

    PubMed

    Niu, Chen; Liu, Xin; Yang, Yong; Zhang, Kun; Min, Zhigang; Wang, Maode; Li, Wenfei; Guo, Liping; Lin, Pan; Zhang, Ming

    2016-03-01

    Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) techniques are widely used for identifying the corticospinal tract (CST) white matter pathways as part of presurgical planning. However, mass effects in patients with brain tumors tend to cause anatomical distortions and compensatory functional reorganization of the cortex, which may lead to inaccurate mapping of white matter tracts. To overcome these problems, we compared different region-of-interest (ROI) selection schemes to track CST fibers in patients with brain tumors. Our study investigated the CSTs of 16 patients with intracranial tumors. The patients were classified into 3 subgroups according to the spatial relationships of the lesion and the primary motor cortex (PMC)/internal capsule. Specifically, we investigated the key factors that cause distorted tractography in patients with tumors. We compared 3 CST tractography methods that used different ROI selection schemes. The results indicate that CST fiber tracking methods based only on anatomical ROIs could possibly lead to distortions near the PMC region and may be unable to effectively localize the PMC. In contrast, the dual ROI method, which uses ROIs that have been selected from both blood oxygen level-dependent functional MRI (BOLD-fMRI) activation and anatomical landmarks, enabled the tracking of fibers to the motor cortex. The results demonstrate that the dual ROI method can localize the entire CST fiber pathway and can accurately describe the spatial relationships of CST fibers relative to the tumor. These results illustrate the reliability of using fMRI-guided DTT in patients with tumors. The combination of fMRI and anatomical information enhances the identification of tracts of interest in brains with anatomical deformations, which provides neurosurgeons with a more accurate approach for visualizing and localizing white matter fiber tracts in patients with brain tumors. This approach enhances surgical performance and perserves

  6. Assessing Region of Interest Schemes for the Corticospinal Tract in Patients With Brain Tumors

    PubMed Central

    Niu, Chen; Liu, Xin; Yang, Yong; Zhang, Kun; Min, Zhigang; Wang, Maode; Li, Wenfei; Guo, Liping; Lin, Pan; Zhang, Ming

    2016-01-01

    Abstract Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) techniques are widely used for identifying the corticospinal tract (CST) white matter pathways as part of presurgical planning. However, mass effects in patients with brain tumors tend to cause anatomical distortions and compensatory functional reorganization of the cortex, which may lead to inaccurate mapping of white matter tracts. To overcome these problems, we compared different region-of-interest (ROI) selection schemes to track CST fibers in patients with brain tumors. Our study investigated the CSTs of 16 patients with intracranial tumors. The patients were classified into 3 subgroups according to the spatial relationships of the lesion and the primary motor cortex (PMC)/internal capsule. Specifically, we investigated the key factors that cause distorted tractography in patients with tumors. We compared 3 CST tractography methods that used different ROI selection schemes. The results indicate that CST fiber tracking methods based only on anatomical ROIs could possibly lead to distortions near the PMC region and may be unable to effectively localize the PMC. In contrast, the dual ROI method, which uses ROIs that have been selected from both blood oxygen level-dependent functional MRI (BOLD-fMRI) activation and anatomical landmarks, enabled the tracking of fibers to the motor cortex. The results demonstrate that the dual ROI method can localize the entire CST fiber pathway and can accurately describe the spatial relationships of CST fibers relative to the tumor. These results illustrate the reliability of using fMRI-guided DTT in patients with tumors. The combination of fMRI and anatomical information enhances the identification of tracts of interest in brains with anatomical deformations, which provides neurosurgeons with a more accurate approach for visualizing and localizing white matter fiber tracts in patients with brain tumors. This approach enhances surgical performance and

  7. 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.

  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. 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.

  10. Balancing grief and survival: Experiences of children with brain tumors and their parents.

    PubMed

    Eaton Russell, Ceilidh; Bouffet, Eric; Beaton, John; Lollis, Susan

    2016-01-01

    Psychosocial research about childhood brain tumors is limited because of varied abilities and prognoses, with children's voices largely absent. Research has focused on the impacts on families and their reactions; this qualitative study used constructivist grounded theory methods to explore experiences of childhood brain tumors from the perspectives of 12 children and 12 parents using semistructured interviews. Their stories illustrated efforts to maintain positivity and normalcy as they faced grief and uncertainty. The substantive grounded theory of balancing grief and survival offers a lens through which to view children's and parents' complex experiences, struggles, and coping strategies as integrated, dynamic processes. PMID:27435121

  11. The family impacts of proton radiation therapy for children with brain tumors.

    PubMed

    Houtrow, Amy J; Yock, Torunn I; Delahaye, Jennifer; Kuhlthau, Karen

    2012-01-01

    Children with brain tumors experience significant alterations to their health and well-being due to the tumors themselves and oncologic treatment. Caring for children with brain tumors can have significant impacts on families, especially during and shortly after treatment. In this study of the impacts on families caring for children undergoing proton radiation therapy for brain tumors, the authors found that families experienced a broad array of negative impacts. Families reported feeling like they were living on a roller coaster, feeling that others treated them differently, and having to give up things as a family. In the multivariable linear regression model, older age of the child and higher reported child health-related quality of life were associated with less family impact. The presence of concurrent chemotherapy was associated with increased family impact. This is the first study to specifically evaluate the families of children being treated with proton radiation therapy. The findings in this study are consistent with the findings in other studies of children treated with standard therapy that show that families experience a variety of stressors and negative impacts while their children are receiving treatment. Health care providers should be aware of the potential impacts on families of children with brain tumors and their treatment to provide robust services to meet the health, psychological, and social needs of such children and their families. PMID:22647729

  12. Potential risk factors for brain tumors in children. An analysis of 200 cases.

    PubMed

    Giuffrè, R; Liccardo, G; Pastore, F S; Spallone, A; Vagnozzi, R

    1990-01-01

    Two hundred cases of verified brain tumors occurring in patients under 15 years of age were studied in relation to possible etiologic, genetic, and environmental risk factors. They were compared with 100 age-matched patients harboring solid neoplasms outside the nervous system, as well as with 100 normal children. In our study, first-degree relatives of a brain tumor child did not show a higher incidence of either tumors or of epilepsy and strokes as compared with controls. First-born children (46%) with higher birth weights showed a greater tendency to present brain tumors. Dystocia (18.5%), previous miscarriages (18%), and dietary restrictions during pregnancy (3%) were also noted in this study and compared with data in the literature. No evidence of a role of maternal chickenpox and toxoplasmosis could be found. The pharmacological risk also seemed to be minimal. The mother's hormonal profile is deduced from the age at menarche and delivery, as well as from a tendency to miscarriages and complicated pregnancies. With regard to the immunologic aspect, it is worth noting that 15% of the mothers complained of allergies. Live polio vaccine and zoonosis might suggest a possible role of virus-related factors in the oncogenesis of brain tumors in children. Radiation-related risk is possibly present in less than 5% of cases. Parental occupation is not relevant in this series.

  13. Quick detection of brain tumors and edemas: a bounding box method using symmetry.

    PubMed

    Saha, Baidya Nath; Ray, Nilanjan; Greiner, Russell; Murtha, Albert; Zhang, Hong

    2012-03-01

    A significant medical informatics task is indexing patient databases according to size, location, and other characteristics of brain tumors and edemas, possibly based on magnetic resonance (MR) imagery. This requires segmenting tumors and edemas within images from different MR modalities. To date, automated brain tumor or edema segmentation from MR modalities remains a challenging, computationally intensive task. In this paper, we propose a novel automated, fast, and approximate segmentation technique. The input is a patient study consisting of a set of MR slices, and its output is a subset of the slices that include axis-parallel boxes that circumscribe the tumors. Our approach is based on an unsupervised change detection method that searches for the most dissimilar region (axis-parallel bounding boxes) between the left and the right halves of a brain in an axial view MR slice. This change detection process uses a novel score function based on Bhattacharya coefficient computed with gray level intensity histograms. We prove that this score function admits a very fast (linear in image height and width) search to locate the bounding box. The average dice coefficients for localizing brain tumors and edemas, over ten patient studies, are 0.57 and 0.52, respectively, which significantly exceeds the scores for two other competitive region-based bounding box techniques. PMID:21719256

  14. Raman spectroscopic imaging as complementary tool for histopathologic assessment of brain tumors

    NASA Astrophysics Data System (ADS)

    Krafft, Christoph; Bergner, Norbert; Romeike, Bernd; Reichart, Rupert; Kalff, Rolf; Geiger, Kathrin; Kirsch, Matthias; Schackert, Gabriele; Popp, Jürgen

    2012-02-01

    Raman spectroscopy enables label-free assessment of brain tissues and tumors based on their biochemical composition. Combination of the Raman spectra with the lateral information allows grading of tumors, determining the primary tumor of brain metastases and delineating tumor margins - even during surgery after coupling with fiber optic probes. This contribution presents exemplary Raman spectra and images collected from low grade and high grade regions of astrocytic gliomas and brain metastases. A region of interest in dried tissue sections encompassed slightly increased cell density. Spectral unmixing by vertex component analysis (VCA) and N-FINDR resolved cell nuclei in score plots and revealed the spectral contributions of nucleic acids, cholesterol, cholesterol ester and proteins in endmember signatures. The results correlated with the histopathological analysis after staining the specimens by hematoxylin and eosin. For a region of interest in non-dried, buffer immersed tissue sections image processing was not affected by drying artifacts such as denaturation of biomolecules and crystallization of cholesterol. Consequently, the results correspond better to in vivo situations. Raman spectroscopic imaging of a brain metastases from renal cell carcinoma showed an endmember with spectral contributions of glycogen which can be considered as a marker for this primary tumor.

  15. Notching on Cancer’s Door: Notch Signaling in Brain Tumors

    PubMed Central

    Teodorczyk, Marcin; Schmidt, Mirko H. H.

    2015-01-01

    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

  16. Science to Practice: Can Focused Ultrasound Disruption of the Blood-Brain Barrier Improve Malignant Brain Tumor Treatment Outcomes?

    PubMed

    Bryan, R Nick

    2016-10-01

    A relatively novel combination treatment for malignant brain tumors that includes focused ultrasound has been shown to improve tumor response and treatment outcome in a preclinical mouse model. This method directly addresses the great need for better treatments for this lethal disease. However, there are substantial technologic hurdles that must be addressed before clinical efficacy will be known. Unfortunately, few of these questions can be readily answered outside the clinical environment. Although it would be enormously challenging, a phase I clinical trial seems feasible and needed to determine the clinical value of this technique. PMID:27643762

  17. Signs and symptoms of pediatric brain tumors and diagnostic value of preoperative EEG.

    PubMed

    Preuß, Matthias; Preiss, Sophia; Syrbe, Steffen; Nestler, Ulf; Fischer, Lars; Merkenschlager, Andreas; Bertsche, Astrid; Christiansen, Holger; Bernhard, Matthias K

    2015-11-01

    In pediatric patients, brain tumors have been estimated to be the cause for seizures in only 0.2-0.3% of cases, whereas seizures occurred in about 13% of pediatric brain tumor patients at presentation. This survey was conducted to analyze EEG findings in pediatric tumor patients over the past 14 years to evaluate the diagnostic value of preoperative EEG for diagnosis of brain tumors. Surface EEG was obtained in awake patients using the international 10- to 20-electrode placement in all pediatric patients with intracranial neoplasms between 2000 and 2013 at the University Hospital of Leipzig except for those who needed emergency operative treatment. One hundred forty-two pediatric patients with 80 infratentorial and 62 supratentorial tumors (WHO grades I-II: 91 patients; WHO grades III-IV: 46 patients). Symptomatic hydrocephalus was found in 37. Sensitivity and specificity of ophthalmologic examination for predicting hydrocephalus was 0.39 and 0.72. Preoperative EEG has been conducted in 116 patients, showing normal activity in 54 patients (47%). Out of 62 pathologic EEGs, 40 indicated correctly to the site of the lesion, 15 were pathologic despite of infratentorial location of the tumor. Nineteen patients had a history of seizures of which six had normal EEGs. Sensitivity for and specificity of EEG examination for symptomatic epilepsy was 0.68 and 0.7. Conclusion Preoperative routine EEG provides no additional value in the diagnostic algorithm of pediatric train tumors. The low specificity and sensitivity of EEG (even in patients with clinical seizures as primary symptom of a brain tumor) underline that EEG does not contribute to diagnosis and a normal EEG might even delay correct diagnosis.

  18. Laser induced thermal therapy (LITT) for pediatric brain tumors: case-based review

    PubMed Central

    Riordan, Margaret

    2014-01-01

    Integration of Laser induced thermal therapy (LITT) to magnetic resonance imaging (MRI) have created new options for treating surgically challenging tumors in locations that would otherwise have represented an intrinsic comorbidity by the approach itself. As new applications and variations of the use are discussed, we present a case-based review of the history, development, and subsequent updates of minimally invasive MRI-guided laser interstitial thermal therapy (MRgLITT) ablation in pediatric brain tumors. PMID:26835340

  19. Brain tumor classification and segmentation using sparse coding and dictionary learning.

    PubMed

    Salman Al-Shaikhli, Saif Dawood; Yang, Michael Ying; Rosenhahn, Bodo

    2016-08-01

    This paper presents a novel fully automatic framework for multi-class brain tumor classification and segmentation using a sparse coding and dictionary learning method. The proposed framework consists of two steps: classification and segmentation. The classification of the brain tumors is based on brain topology and texture. The segmentation is based on voxel values of the image data. Using K-SVD, two types of dictionaries are learned from the training data and their associated ground truth segmentation: feature dictionary and voxel-wise coupled dictionaries. The feature dictionary consists of global image features (topological and texture features). The coupled dictionaries consist of coupled information: gray scale voxel values of the training image data and their associated label voxel values of the ground truth segmentation of the training data. For quantitative evaluation, the proposed framework is evaluated using different metrics. The segmentation results of the brain tumor segmentation (MICCAI-BraTS-2013) database are evaluated using five different metric scores, which are computed using the online evaluation tool provided by the BraTS-2013 challenge organizers. Experimental results demonstrate that the proposed approach achieves an accurate brain tumor classification and segmentation and outperforms the state-of-the-art methods.

  20. 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

  1. Evaluation of Vascular Supply with Angio-Computed Tomography During Intra-Arterial Chemotherapy for Brain Tumors

    SciTech Connect

    Hirai, Toshinori Korogi, Yukunori; Ono, Ken; Yamashita, Yasuyuki

    2005-04-15

    We report the utility of a combined angiography and computed tomography (angio-CT) system in assessing drug distribution to the tumor during intra-arterial chemotherapy for metastatic brain tumors in a 65-year-old man. Although digital subtraction angiography did not clearly show tumor perfusion in two cerebellar tumors, angio-CT provided definite tumor perfusion in the complicated vascular territory, and anticancer agents were infused based on its findings. To our knowledge, however, this application for intra-arterial chemotherapy of brain tumors has not been previously described.

  2. [Suspicion of anorexia nervosa as a cause of delayed diagnosis of brain tumor. A case report].

    PubMed

    Niedzielska, Ewa; Węcławek-Tompol, Jadwiga; Kazanowska, Bernarda; Barg, Ewa

    2015-01-01

    Tumors of the central nervous system (CNS) are the most common solid tumors diagnosed in children. The most frequent symptoms of brain tumors in this age group are headaches and vomiting, regardless of the location of the lesions. These symptoms are non-specific, and in each case require differential diagnosis, especially if there is no gradual improvement in the patient's condition or progression. The most common signs of anorexia nervosa are chronic vomiting, weakness of the body, pain and in extreme cases cachexia. These symptoms are similar to the clinical image of CNS tumor. Teenager, described in our case report presented the following signs for several weeks prior to the diagnosis of a brain tumor: vomiting (especially after meals), non-specific headache and epigastric pain. No significant progression in the patient's condition oriented the diagnostic process towards anorexia nervosa. Although anorexia in this age group is much more common disease, compared to a brain tumor, it is vital to ruled out/ exclude organic disorders prior to diagnosis of psychogenic disorder. At the same time the waiting for the specialist consultations (ophthalmologist, neurologist) and test results (head CT, head NMR) should not prolong the patients referral to a specialist center. PMID:26615049

  3. Use of complementary and alternative medical therapy by patients with primary brain tumors.

    PubMed

    Armstrong, Terri S; Gilbert, Mark R

    2008-05-01

    The use of complementary and alternative medicine (CAM) is increasing. CAM includes mind-body interventions, biologically based therapies, energy therapies, and body-based methods. Primary brain tumors arise within the brain and have a poor prognosis when malignant. Even patients with benign tumors suffer neurologic and systemic symptoms as a result of the tumor or its treatment. CAM is used by 30% of brain tumor patients, who often do not report its use to their physician. Herbal medicines may affect the metabolism of prescribed medications or produce adverse effects that may be attributed to other causes. In patients with systemic cancer, mind-body modalities such as meditation and relaxation therapy have been shown to be helpful in reducing anxiety and pain; acupuncture and hypnotherapy may also reduce both pain and nausea. Recent preclinical studies have reported that ginseng, Scutellaria baicalensis, and Angelica sinensis may promote apoptosis of tumor cells or exercise antiangiogenic effects. Further studies are needed to evaluate the impact of CAM on symptom control or tumor growth in this vulnerable patient population.

  4. Semi-automatic segmentation of brain tumors using population and individual information.

    PubMed

    Wu, Yao; Yang, Wei; Jiang, Jun; Li, Shuanqian; Feng, Qianjin; Chen, Wufan

    2013-08-01

    Efficient segmentation of tumors in medical images is of great practical importance in early diagnosis and radiation plan. This paper proposes a novel semi-automatic segmentation method based on population and individual statistical information to segment brain tumors in magnetic resonance (MR) images. First, high-dimensional image features are extracted. Neighborhood components analysis is proposed to learn two optimal distance metrics, which contain population and patient-specific information, respectively. The probability of each pixel belonging to the foreground (tumor) and the background is estimated by the k-nearest neighborhood classifier under the learned optimal distance metrics. A cost function for segmentation is constructed through these probabilities and is optimized using graph cuts. Finally, some morphological operations are performed to improve the achieved segmentation results. Our dataset consists of 137 brain MR images, including 68 for training and 69 for testing. The proposed method overcomes segmentation difficulties caused by the uneven gray level distribution of the tumors and even can get satisfactory results if the tumors have fuzzy edges. Experimental results demonstrate that the proposed method is robust to brain tumor segmentation. PMID:23319111

  5. A longitudinal magnetic resonance elastography study of murine brain tumors following radiation therapy

    NASA Astrophysics Data System (ADS)

    Feng, Y.; Clayton, E. H.; Okamoto, R. J.; Engelbach, J.; Bayly, P. V.; Garbow, J. R.

    2016-08-01

    An accurate and noninvasive method for assessing treatment response following radiotherapy is needed for both treatment monitoring and planning. Measurement of solid tumor volume alone is not sufficient for reliable early detection of therapeutic response, since changes in physiological and/or biomechanical properties can precede tumor volume change following therapy. In this study, we use magnetic resonance elastography to evaluate the treatment effect after radiotherapy in a murine brain tumor model. Shear modulus was calculated and compared between the delineated tumor region of interest (ROI) and its contralateral, mirrored counterpart. We also compared the shear modulus from both the irradiated and non-irradiated tumor and mirror ROIs longitudinally, sampling four time points spanning 9–19 d post tumor implant. Results showed that the tumor ROI had a lower shear modulus than that of the mirror ROI, independent of radiation. The shear modulus of the tumor ROI decreased over time for both the treated and untreated groups. By contrast, the shear modulus of the mirror ROI appeared to be relatively constant for the treated group, while an increasing trend was observed for the untreated group. The results provide insights into the tumor properties after radiation treatment and demonstrate the potential of using the mechanical properties of the tumor as a biomarker. In future studies, more closely spaced time points will be employed for detailed analysis of the radiation effect.

  6. A longitudinal magnetic resonance elastography study of murine brain tumors following radiation therapy

    NASA Astrophysics Data System (ADS)

    Feng, Y.; Clayton, E. H.; Okamoto, R. J.; Engelbach, J.; Bayly, P. V.; Garbow, J. R.

    2016-08-01

    An accurate and noninvasive method for assessing treatment response following radiotherapy is needed for both treatment monitoring and planning. Measurement of solid tumor volume alone is not sufficient for reliable early detection of therapeutic response, since changes in physiological and/or biomechanical properties can precede tumor volume change following therapy. In this study, we use magnetic resonance elastography to evaluate the treatment effect after radiotherapy in a murine brain tumor model. Shear modulus was calculated and compared between the delineated tumor region of interest (ROI) and its contralateral, mirrored counterpart. We also compared the shear modulus from both the irradiated and non-irradiated tumor and mirror ROIs longitudinally, sampling four time points spanning 9-19 d post tumor implant. Results showed that the tumor ROI had a lower shear modulus than that of the mirror ROI, independent of radiation. The shear modulus of the tumor ROI decreased over time for both the treated and untreated groups. By contrast, the shear modulus of the mirror ROI appeared to be relatively constant for the treated group, while an increasing trend was observed for the untreated group. The results provide insights into the tumor properties after radiation treatment and demonstrate the potential of using the mechanical properties of the tumor as a biomarker. In future studies, more closely spaced time points will be employed for detailed analysis of the radiation effect.

  7. [Results of surgical treatment of malignant brain tumors].

    PubMed

    Goldhahn, W E

    1987-05-29

    Although surgical treatment seldom cures any malignant brain tumours, it remains the basis of the management of these tumours. Studies by others and our own statistical studies demonstrate the absence of any real or significant improvement in survival time for most of the patients. Hence we must await progress in other oncological disciplines to provide a solution.

  8. A novel content-based active contour model for brain tumor segmentation.

    PubMed

    Sachdeva, Jainy; Kumar, Vinod; Gupta, Indra; Khandelwal, Niranjan; Ahuja, Chirag Kamal

    2012-06-01

    Brain tumor segmentation is a crucial step in surgical and treatment planning. Intensity-based active contour models such as gradient vector flow (GVF), magneto static active contour (MAC) and fluid vector flow (FVF) have been proposed to segment homogeneous objects/tumors in medical images. In this study, extensive experiments are done to analyze the performance of intensity-based techniques for homogeneous tumors on brain magnetic resonance (MR) images. The analysis shows that the state-of-art methods fail to segment homogeneous tumors against similar background or when these tumors show partial diversity toward the background. They also have preconvergence problem in case of false edges/saddle points. However, the presence of weak edges and diffused edges (due to edema around the tumor) leads to oversegmentation by intensity-based techniques. Therefore, the proposed method content-based active contour (CBAC) uses both intensity and texture information present within the active contour to overcome above-stated problems capturing large range in an image. It also proposes a novel use of Gray-Level Co-occurrence Matrix to define texture space for tumor segmentation. The effectiveness of this method is tested on two different real data sets (55 patients - more than 600 images) containing five different types of homogeneous, heterogeneous, diffused tumors and synthetic images (non-MR benchmark images). Remarkable results are obtained in segmenting homogeneous tumors of uniform intensity, complex content heterogeneous, diffused tumors on MR images (T1-weighted, postcontrast T1-weighted and T2-weighted) and synthetic images (non-MR benchmark images of varying intensity, texture, noise content and false edges). Further, tumor volume is efficiently extracted from 2-dimensional slices and is named as 2.5-dimensional segmentation. PMID:22459443

  9. Temozolomide and O6-Benzylguanine in Treating Children With Recurrent 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 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

  10. [The first experience in interstitial brachytherapy for primary and metastatic tumors of the brain].

    PubMed

    Bentsion, D L; Gvozdev, P B; Sakovich, V P; Fialko, N V; Kolotvinov, V S; Baiankina, S N

    2006-01-01

    In 2001-2002, the authors performed a course of brachytherapy in 15 patients with inoperable primary, recurrent, and metastatic brain tumors. The histostructural distribution was as follows: low-grade astrocytoma (grade II according to the WHO classification) in 2 patients, anaplastic astrocytoma (AA) in 3, glioblastoma multiforme (GBM) in 5. Five patients had solid tumor deposits in the brain. Computer tomographic (CT) and magnetic resonance imaging (MRI) data were used to define a path for forthcoming biopsy and implantation at a "Stryker" navigation station, by taking into account the anatomy of the brain, vessels, and functionally significant areas. After having histological findings, plastic intrastats whose number had been determined by the volume of a target were implanted into a tumor by the predetermined path. Dosimetric planning was accomplished by using CT and MRI images on an "Abacus" system. The final stage involved irradiation on a "GammaMed plus" with a source of 192Ir. Irradiation was given, by hyperfractionating its dose (3-4 Gy twice daily at an interval of 4-5 hours) to the total focal dose (TFD) of 36-44 Gy. Patients with gliomas untreated with radiation also underwent external radiation in a TFD of 54-56 Gy and patients with brain metastases received total external irradiation of the brain in a TFD of 36-40 Gy. The tolerance of a course of irradiation was fair. In patients with AA and GBM, one-year survival was observed in 66 and 60%, respectively; in those having metastasis, it was in 20%. Six patients died from progressive disease. All patients with low-grade astrocytoma and one patient with anaplastic astrocytoma were alive at month 24 after treatment termination. The mean lifespan of patients with malignant gliomas and solid tumor metastasis was 11.5 and 5.8 months, respectively. Brachytherapy is a noninvasive and tolerable mode of radiotherapy that increases survival in some groups of patients with inoperable brain tumors.

  11. Effect of disease and recovery on functional anatomy in brain tumor patients: insights from functional MRI and diffusion tensor imaging

    PubMed Central

    Abd-El-Barr, Muhammad M; Saleh, Emam; Huang, Raymond Y; Golby, Alexandra J

    2014-01-01

    Patients with brain tumors provide a unique opportunity to understand functional brain plasticity. Using advanced imaging techniques, such as functional MRI and diffusion tensor imaging, we have gained tremendous knowledge of brain tumor behavior, transformation, infiltration and destruction of nearby structures. Using these advanced techniques as an adjunct with more proven techniques, such as direct cortical stimulation, intraoperative navigation and advanced microsurgical techniques, we now are able to better formulate safer resection trajectories, perform larger resections at reduced risk and better counsel patients and their families about possible complications. Brain mapping in patients with brain tumors and other lesions has shown us that the old idea of fixed function of the adult cerebral cortex is not entirely true. Improving care for patients with brain lesions in the future will depend on better understanding of the functional organization and plasticity of the adult brain. Advanced noninvasive brain imaging will undoubtedly play a role in advancing this understanding. PMID:24660024

  12. Clinical Evaluation of a Fully-automatic Segmentation Method for Longitudinal Brain Tumor Volumetry.

    PubMed

    Meier, Raphael; Knecht, Urspeter; Loosli, Tina; Bauer, Stefan; Slotboom, Johannes; Wiest, Roland; Reyes, Mauricio

    2016-01-01

    Information about the size of a tumor and its temporal evolution is needed for diagnosis as well as treatment of brain tumor patients. The aim of the study was to investigate the potential of a fully-automatic segmentation method, called BraTumIA, for longitudinal brain tumor volumetry by comparing the automatically estimated volumes with ground truth data acquired via manual segmentation. Longitudinal Magnetic Resonance (MR) Imaging data of 14 patients with newly diagnosed glioblastoma encompassing 64 MR acquisitions, ranging from preoperative up to 12 month follow-up images, was analysed. Manual segmentation was performed by two human raters. Strong correlations (R = 0.83-0.96, p < 0.001) were observed between volumetric estimates of BraTumIA and of each of the human raters for the contrast-enhancing (CET) and non-enhancing T2-hyperintense tumor compartments (NCE-T2). A quantitative analysis of the inter-rater disagreement showed that the disagreement between BraTumIA and each of the human raters was comparable to the disagreement between the human raters. In summary, BraTumIA generated volumetric trend curves of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments comparable to estimates of human raters. These findings suggest the potential of automated longitudinal tumor segmentation to substitute manual volumetric follow-up of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments. PMID:27001047

  13. Clinical Evaluation of a Fully-automatic Segmentation Method for Longitudinal Brain Tumor Volumetry

    NASA Astrophysics Data System (ADS)

    Meier, Raphael; Knecht, Urspeter; Loosli, Tina; Bauer, Stefan; Slotboom, Johannes; Wiest, Roland; Reyes, Mauricio

    2016-03-01

    Information about the size of a tumor and its temporal evolution is needed for diagnosis as well as treatment of brain tumor patients. The aim of the study was to investigate the potential of a fully-automatic segmentation method, called BraTumIA, for longitudinal brain tumor volumetry by comparing the automatically estimated volumes with ground truth data acquired via manual segmentation. Longitudinal Magnetic Resonance (MR) Imaging data of 14 patients with newly diagnosed glioblastoma encompassing 64 MR acquisitions, ranging from preoperative up to 12 month follow-up images, was analysed. Manual segmentation was performed by two human raters. Strong correlations (R = 0.83–0.96, p < 0.001) were observed between volumetric estimates of BraTumIA and of each of the human raters for the contrast-enhancing (CET) and non-enhancing T2-hyperintense tumor compartments (NCE-T2). A quantitative analysis of the inter-rater disagreement showed that the disagreement between BraTumIA and each of the human raters was comparable to the disagreement between the human raters. In summary, BraTumIA generated volumetric trend curves of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments comparable to estimates of human raters. These findings suggest the potential of automated longitudinal tumor segmentation to substitute manual volumetric follow-up of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments.

  14. 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

  15. Transport processes in biological systems: Tumoral cells and human brain

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto

    2014-01-01

    The entropy generation approach has been developed for the analysis of complex systems, with particular regards to biological systems, in order to evaluate their stationary states. The entropy generation is related to the transport processes related to exergy flows. Moreover, cancer can be described as an open complex dynamic and self-organizing system. Consequently, it is used as an example useful to evaluate the different thermo-chemical quantities of the transport processes in normal and in tumoral cells systems.

  16. Advanced Imaging for Biopsy Guidance in Primary Brain Tumors

    PubMed Central

    Tsiouris, Apostolos J; Ramakrishna, Rohan

    2016-01-01

    Accurate glioma sampling is required for diagnosis and establishing eligibility for relevant clinical trials. MR-based perfusion and spectroscopy sequences supplement conventional MR in noninvasively predicting the areas of highest tumor grade for biopsy. We report the case of a patient with gliomatosis cerebri and multifocal patchy enhancement in whom the combination of advanced and conventional imaging attributes successfully guided a diagnostic biopsy. PMID:27014538

  17. Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases.

    PubMed

    Thorsen, Frits; Fite, Brett; Mahakian, Lisa M; Seo, Jai W; Qin, Shengping; Harrison, Victoria; Johnson, Sarah; Ingham, Elizabeth; Caskey, Charles; Sundstrøm, Terje; Meade, Thomas J; Harter, Patrick N; Skaftnesmo, Kai Ove; Ferrara, Katherine W

    2013-12-28

    Our goal was to develop strategies to quantify the accumulation of model therapeutics in small brain metastases using multimodal imaging, in order to enhance the potential for successful treatment. Human melanoma cells were injected into the left cardiac ventricle of immunodeficient mice. Bioluminescent, MR and PET imaging were applied to evaluate the limits of detection and potential for contrast agent extravasation in small brain metastases. A pharmacokinetic model was applied to estimate vascular permeability. Bioluminescent imaging after injecting d-luciferin (molecular weight (MW) 320 D) suggested that tumor cell extravasation had already occurred at week 1, which was confirmed by histology. 7T T1w MRI at week 4 was able to detect non-leaky 100 μm sized lesions and leaky tumors with diameters down to 200 μm after contrast injection at week 5. PET imaging showed that (18)F-FLT (MW 244 Da) accumulated in the brain at week 4. Gadolinium-based MRI tracers (MW 559 Da and 2.066 kDa) extravasated after 5 weeks (tumor diameter 600 μm), and the lower MW agent cleared more rapidly from the tumor (mean apparent permeabilities 2.27 × 10(-5)cm/s versus 1.12 × 10(-5)cm/s). PET imaging further demonstrated tumor permeability to (64)Cu-BSA (MW 65.55 kDa) at week 6 (tumor diameter 700 μm). In conclusion, high field T1w MRI without contrast may improve the detection limit of small brain metastases, allowing for earlier diagnosis of patients, although the smallest lesions detected with T1w MRI were permeable only to d-luciferin and the amphipathic small molecule (18)F-FLT. Different-sized MR and PET contrast agents demonstrated the gradual increase in leakiness of the blood tumor barrier during metastatic progression, which could guide clinicians in choosing tailored treatment strategies.

  18. Brain atlas deformation in the presence of small and large space-occupying tumors.

    PubMed

    Dawant, B M; Hartmann, S L; Pan, Shiyan; Gadamsetty, S

    2002-01-01

    Brain atlases contain a wealth of information that could be used in radiation therapy or neurosurgical planning. Until now, however, when large space-occupying tumors and lesions drastically alter the shape of brain structures and substructures, atlas-based methods have been of limited use. In this work, we present a new technique that permits a brain atlas to be warped onto image volumes in which large lesions are present. First we show that a method previously used for atlas-based segmentation of normal brains can also be used for brains with small lesions. We then present an extension of this technique for brains with large lesions. This involves several steps: a global registration to bring the two volumes into approximate correspondence; a local registration to warp the atlas onto the patient volume; the seeding of the warped atlas with a tumor model derived from patient data; and the deformation of the seeded atlas. Global registration is performed using a mutual information criterion. The method we have used for atlas warping is derived from optical flow principles. Preliminary results obtained on real patient images are presented. These results indicate that the proposed method can be used to automatically segment structures of interest in brains with gross deformation. Potential areas of application for this method include automatic labeling of critical structures for radiation therapy and presurgical planning. PMID:12173876

  19. 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.

  20. High-resolution whole-brain DCE-MRI using constrained reconstruction: Prospective clinical evaluation in brain tumor patients

    PubMed Central

    Guo, Yi; Lebel, R. Marc; Zhu, Yinghua; Lingala, Sajan Goud; Shiroishi, Mark S.; Law, Meng; Nayak, Krishna

    2016-01-01

    Purpose: To clinically evaluate a highly accelerated T1-weighted dynamic contrast-enhanced (DCE) MRI technique that provides high spatial resolution and whole-brain coverage via undersampling and constrained reconstruction with multiple sparsity constraints. Methods: Conventional (rate-2 SENSE) and experimental DCE-MRI (rate-30) scans were performed 20 minutes apart in 15 brain tumor patients. The conventional clinical DCE-MRI had voxel dimensions 0.9 × 1.3 × 7.0 mm3, FOV 22 × 22 × 4.2 cm3, and the experimental DCE-MRI had voxel dimensions 0.9 × 0.9 × 1.9 mm3, and broader coverage 22 × 22 × 19 cm3. Temporal resolution was 5 s for both protocols. Time-resolved images and blood–brain barrier permeability maps were qualitatively evaluated by two radiologists. Results: The experimental DCE-MRI scans showed no loss of qualitative information in any of the cases, while achieving substantially higher spatial resolution and whole-brain spatial coverage. Average qualitative scores (from 0 to 3) were 2.1 for the experimental scans and 1.1 for the conventional clinical scans. Conclusions: The proposed DCE-MRI approach provides clinically superior image quality with higher spatial resolution and coverage than currently available approaches. These advantages may allow comprehensive permeability mapping in the brain, which is especially valuable in the setting of large lesions or multiple lesions spread throughout the brain. PMID:27147313

  1. Use of preoperative FLAIR MRI and ependymal proximity of tumor enhancement as surrogate markers of brain tumor origin.

    PubMed

    Smith, Timothy R; Hulou, M Maher; Abecassis, Josh; Das, Sunit; Chandler, James P

    2015-09-01

    Neural stem cells proliferate in the subventricular zone and give rise to progeny that differentiate and migrate throughout the brain. We aimed to test the hypothesis that glioma behavior and grade may correlate with the identity of the tumor cell of origin. We evaluated three preoperative radiographic features (fluid attenuated inversion recovery [FLAIR] MRI characteristics, tumor proximity to ventricular ependyma, and subependymal representation) as surrogate markers of tumor origin using a retrospective cohort design. The medical records of 228 patients who underwent surgical resection of a glioma from January 2004 to August 2008 were reviewed. Average patient age was 54.5 years (standard deviation [SD] 15.3) with a male predominance (62.9%). World Health Organization glioma grades amongst the cohort were Grade IV (71.6%), Grade III (21.3%) and Grade II (7.1%). Mean survival was 11.2 months (SD 10.5) with a mean follow up of 12.8 months (SD 11.3). Glioma tumor grade was significantly correlated to FLAIR signal proximity to the ependymal surface (p<0.01) and inversely with proximity of tumor mass to the ependyma (p<0.01). The mean distance of tumor-associated FLAIR signal from the ependymal surface for glioblastoma multiforme (GBM) was 1.2mm (SD 3.3) compared to 4.8 (SD 6.5) for anaplastic astrocytomas and 6.6mm (SD 6.7; p<0.01) for low grade gliomas. Conversely, the mean distance of the enhancing tumor mass from the ependyma for GBM was 7.3mm (SD 9.4), Grade III glioma 2.3mm (SD 4.9), and Grade II glioma 3.8mm (SD 6.8; p<0.05). These findings suggest that higher grade gliomas might arise from less differentiated neuroepithelial cells in the subventricular zone that possess greater migratory potential.

  2. Chondroitin Sulfate Proteoglycans Potently Inhibit Invasion and Serve as a Central Organizer of the Brain Tumor Microenvironment

    PubMed Central

    Siebzehnrubl, Florian A.; Schildts, Michela J.; Yachnis, Anthony T.; Smith, George M.; Smith, Amy A.; Scheffler, Bjorn; Reynolds, Brent A.; Silver, Jerry; Steindler, Dennis A.

    2013-01-01

    Glioblastoma (GBM) remains the most pervasive and lethal of all brain malignancies. One factor that contributes to this poor prognosis is the highly invasive character of the tumor. GBM is characterized by microscopic infiltration of tumor cells throughout the brain, whereas non-neural metastases, as well as select lower grade gliomas, develop as self-contained and clearly delineated lesions. Illustrated by rodent xenograft tumor models as well as pathological human patient specimens, we present evidence that one fundamental switch between these two distinct pathologies–invasion and noninvasion–is mediated through the tumor extracellular matrix. Specifically, noninvasive lesions are associated with a rich matrix containing substantial amounts of glycosylated chondroitin sulfate proteoglycans (CSPGs), whereas glycosylated CSPGs are essentially absent from diffusely infiltrating tumors. CSPGs, acting as central organizers of the tumor microenvironment, dramatically influence resident reactive astrocytes, inducing their exodus from the tumor mass and the resultant encapsulation of noninvasive lesions. Additionally, CSPGs induce activation of tumor-associated microglia. We demonstrate that the astrogliotic capsule can directly inhibit tumor invasion, and its absence from GBM presents an environment favorable to diffuse infiltration. We also identify the leukocyte common antigen-related phosphatase receptor (PTPRF) as a putative intermediary between extracellular glycosylated CSPGs and noninvasive tumor cells. In all, we present CSPGs as critical regulators of brain tumor histopathology and help to clarify the role of the tumor microenvironment in brain tumor invasion. PMID:24068827

  3. MicroRNA142-3p promotes tumor-initiating and radioresistant properties in malignant pediatric brain tumors.

    PubMed

    Lee, Yi-Yen; Yang, Yi-Ping; Huang, Ming-Chao; Wang, Mong-Lien; Yen, Sang-Hue; Huang, Pin-I; Chen, Yi-Wei; Chiou, Shih-Hwa; Lan, Yuan-Tzu; Ma, Hsin-I; Shih, Yang-Hsin; Chen, Ming-Teh

    2014-01-01

    Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (ATRT) is an extremely malignant pediatric brain tumor observed in infancy and childhood. It has been reported that a subpopulation of CD133(+) cells isolated from ATRT tumors present with cancer stem-like and radioresistant properties. However, the exact biomolecular mechanisms of ATRT or CD133-positive ATRT (ATRT-CD133(+)) cells are still unclear. We have previously shown that ATRT-CD133(+) cells have pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). By using microRNA array and quantitative RT-PCR in this study, we showed that expression of miR142-3p was lower in ATRT-CD133(+) cells than in ATRT-CD133(-) cells. miR142-3p overexpression significantly inhibited the self-renewal and tumorigenicity of ATRT-CD133(+) cells. On the contrary, silencing of endogenous miR142-3p dramatically increased the tumor-initiating and stem-like cell capacities in ATRT cells or ATRT-CD133(-) cells and further promoted the mesenchymal transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT cells effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant properties of malignant pediatric brain cancer stem cells. PMID:24816458

  4. Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors

    NASA Astrophysics Data System (ADS)

    Dixit, Suraj; Novak, Thomas; Miller, Kayla; Zhu, Yun; Kenney, Malcolm E.; Broome, Ann-Marie

    2015-01-01

    Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to untargeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.

  5. Tungsten treatment prevents tumor necrosis factor-induced injury of brain endothelial cells.

    PubMed

    Terada, L S; Willingham, I R; Guidot, D M; Shibao, G N; Kindt, G W; Repine, J E

    1992-02-01

    Exposure to recombinant human tumor necrosis factor-alpha (TNF-alpha) or calcium ionophore (A23187) for 4 h increased (P less than 0.05) lactate dehydrogenase (LDH) release from cultured bovine brain endothelial cells (EC). In contrast, treatment with endotoxin or interleukin-1 did not increase (P greater than 0.05). LDH release from brain EC. Pretreatment with tungsten decreased (P less than 0.05) xanthine oxidase activity in brain EC and decreased (P less than 0.05) LDH release from brain EC following exposure to TNF. Our results suggest that TNF-alpha injures brain microvascular EC and that this effect may be mediated by xanthine oxidase.

  6. Identification of internalizing human single chain antibodies targeting brain tumor sphere cells

    PubMed Central

    Zhu, Xiaodong; Bidlingmaier, Scott; Hashizume, Rintaro; James, C. David; Berger, Mitchel S.; Liu, Bin

    2010-01-01

    Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain tumor and there is no curative treatment to date. Resistance to conventional therapies and tumor recurrence pose major challenges to treatment and management of this disease, and therefore new therapeutic strategies need to be developed. Previous studies by other investigators have shown that a subpopulation of GBM cells can grow as neurosphere-like cells when cultured in restrictive media, and exhibit enhanced tumor initiating ability and resistance to therapy. We report here the identification of internalizing human single chain antibodies (scFvs) targeting GBM tumor sphere cells. We selected a large naive phage antibody display library on the glycosylation-dependent CD133 epitope-positive subpopulation of GBM cells grown as tumor spheres and identified internalizing scFvs that target tumor sphere cells broadly, as well as scFvs that target the CD133 positive subpopulation. These scFvs were found to be efficiently internalized by GBM tumor sphere cells. One scFv GC4 inhibited self-renewal of GBM tumor sphere cells in vitro. We have further developed a full-length human IgG1 based on this scFv and found that it potently inhibits proliferation of GBM tumor sphere cells and GBM cells grown in regular non-selective media. Taken together, these results show that internalizing human scFvs targeting brain tumor sphere cells can be readily identified from a phage antibody display library, which could be useful for further development of novel therapies that target subpopulations of GBM cells to combat recurrence and resistance to treatment. PMID:20587664

  7. Trends in incidence of primary brain tumors in the United States, 1985-1994.

    PubMed Central

    Jukich, P. J.; McCarthy, B. J.; Surawicz, T. S.; Freels, S.; Davis, F. G.

    2001-01-01

    Brain tumor incidence has increased over the last 20 years in all age groups, both overall and for specific histologies. Reasons attributed to these increases include increase in lymphoma due to HIV/AIDS, introduction of computed tomography/magnetic resonance imaging, and changes in coding/classification. The purpose of this study was to describe overall and histologic-specific incidence trends in a population-based series of primary benign and malignant brain tumors. Data from the Central Brain Tumor Registry of the United States from 1985 through 1994 were used to determine incidence trends in the broad age groups 0-19, 20-64, and > or = 65 years, both overall and for selected histologies. Poisson regression was used to express trends as average annual percentage change. Overall, incidence increased modestly (annual percentage change 0.9%, 95% confidence interval, 0.4, 1.4). When lymphomas were excluded, this result was not statistically significant (annual percentage change 0.5%, 95% confidence interval, -0.1, 1.1). Specific histologies that were increasing were lymphomas in individuals aged 20 to 64 years and in males aged 65 years or older, ependymomas in the population aged 20 to 64 years, nerve sheath tumors in males, and pituitary tumors in females. Increases that were not specific to any population subgroup were seen for glioblastoma, oligodendrogliomas, and astrocytomas, excluding not otherwise specified (NOS) tumors. Corresponding decreases were noted for NOS, astrocytoma NOS, and glioma NOS. Increasing incidence trends for lymphomas were consistent with previous literature. Improvements in diagnostic technology in addition to changes in classification and coding were likely to be responsible for decreases seen in incidence of NOS subgroups and corresponding increases in glioma subgroups. In contrast, the increases identified for ependymomas, nerve sheath tumors, and pituitary tumors were less likely to be artifacts of improvements in diagnosis, and they

  8. Retrieval of Brain Tumors by Adaptive Spatial Pooling and Fisher Vector Representation

    PubMed Central

    Huang, Meiyan; Huang, Wei; Jiang, Jun; Zhou, Yujia; Yang, Ru; Zhao, Jie; Feng, Yanqiu; Feng, Qianjin; Chen, Wufan

    2016-01-01

    Content-based image retrieval (CBIR) techniques have currently gained increasing popularity in the medical field because they can use numerous and valuable archived images to support clinical decisions. In this paper, we concentrate on developing a CBIR system for retrieving brain tumors in T1-weighted contrast-enhanced MRI images. Specifically, when the user roughly outlines the tumor region of a query image, brain tumor images in the database of the same pathological type are expected to be returned. We propose a novel feature extraction framework to improve the retrieval performance. The proposed framework consists of three steps. First, we augment the tumor region and use the augmented tumor region as the region of interest to incorporate informative contextual information. Second, the augmented tumor region is split into subregions by an adaptive spatial division method based on intensity orders; within each subregion, we extract raw image patches as local features. Third, we apply the Fisher kernel framework to aggregate the local features of each subregion into a respective single vector representation and concatenate these per-subregion vector representations to obtain an image-level signature. After feature extraction, a closed-form metric learning algorithm is applied to measure the similarity between the query image and database images. Extensive experiments are conducted on a large dataset of 3604 images with three types of brain tumors, namely, meningiomas, gliomas, and pituitary tumors. The mean average precision can reach 94.68%. Experimental results demonstrate the power of the proposed algorithm against some related state-of-the-art methods on the same dataset. PMID:27273091

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

    SciTech Connect

    Soloway, A.H.

    1991-01-01

    Current progress on this research includes the synthesis of chemical structures for malignant brain tumors. These structures include boron-containing derivatives of lipophilic anticonvulsants and CNS depressants; carboranyl precursors of nucleic acids and related structures; and carboranyl amino acids. Cellular uptake and persistence studies have also been carried out with F98 rat glioma cells. 1 fig., 1 tab.

  10. Brain tumors in children and adolescents: cognitive and psychological disorders at different ages.

    PubMed

    Poggi, Geraldina; Liscio, Mariarosaria; Galbiati, Susanna; Adduci, Annarita; Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo; Clerici, Carlo Alfredo; Fossati-Bellani, Franca; Sommovigo, Michela; Castelli, Enrico

    2005-05-01

    Cognitive and psychological disorders are among the most frequently observed sequelae in brain tumor survivors. The goal of this work was to verify the presence of these disorders in a group of children and adolescents diagnosed with brain tumor before age 18 years, differentiate these disorders according to age of assessment, identify correlations between the two types of impairments and define possible associations between these impairments and clinical variables. The study involved 76 patients diagnosed with brain tumor before age 18 years. Three age groups were formed, and all the patients received a standardized battery of age-matched cognitive and psychological tests. According to our findings, all three groups present with cognitive and psychological-behavioral disorders. Their frequency varies according to age of onset and is strongly associated to time since diagnosis. The performance intelligence quotient (PIQ) was more impaired than the verbal intelligence quotient (VIQ). Internalizing problems, withdrawal and social problems were the most frequent psychological disorders. Correlations were found between cognitive impairment and the onset of the main psychological and behavioral disorders. These findings are relevant as they point out the long-term outcome of brain tumor survivors. Hence, the recommendation to diversify psychological interventions and rehabilitation plans according to the patients' age.

  11. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  12. Short Communication: Conformal Therapy for Peri-Ventricular Brain Tumors: Is Target Volume Deformation an Issue?

    SciTech Connect

    Bauman, Glenn Woodford, Curtis; Yartsev, Slav

    2008-04-01

    Physiologic variations in ventricular volumes could have important implications for treating patients with peri-ventricular brain tumors, yet no data exist in the literature addressing this issue. Daily megavoltage computed tomography (CT) scans in a patient with neurocytoma receiving fractionated radiation revealed minimal changes, suggesting that margins accounting for ventricular deformation are not necessary.

  13. Systematic review of wireless phone use and brain cancer and other head tumors.

    PubMed

    Repacholi, Michael H; Lerchl, Alexander; Röösli, Martin; Sienkiewicz, Zenon; Auvinen, Anssi; Breckenkamp, Jürgen; d'Inzeo, Guglielmo; Elliott, Paul; Frei, Patrizia; Heinrich, Sabine; Lagroye, Isabelle; Lahkola, Anna; McCormick, David L; Thomas, Silke; Vecchia, Paolo

    2012-04-01

    We conducted a systematic review of scientific studies to evaluate whether the use of wireless phones is linked to an increased incidence of the brain cancer glioma or other tumors of the head (meningioma, acoustic neuroma, and parotid gland), originating in the areas of the head that most absorb radiofrequency (RF) energy from wireless phones. Epidemiology and in vivo studies were evaluated according to an agreed protocol; quality criteria were used to evaluate the studies for narrative synthesis but not for meta-analyses or pooling of results. The epidemiology study results were heterogeneous, with sparse data on long-term use (≥ 10 years). Meta-analyses of the epidemiology studies showed no statistically significant increase in risk (defined as P < 0.05) for adult brain cancer or other head tumors from wireless phone use. Analyses of the in vivo oncogenicity, tumor promotion, and genotoxicity studies also showed no statistically significant relationship between exposure to RF fields and genotoxic damage to brain cells, or the incidence of brain cancers or other tumors of the head. Assessment of the review results using the Hill criteria did not support a causal relationship between wireless phone use and the incidence of adult cancers in the areas of the head that most absorb RF energy from the use of wireless phones. There are insufficient data to make any determinations about longer-term use (≥ 10 years).

  14. Caring for the brain tumor patient: Family caregiver burden and unmet needs

    PubMed Central

    Schubart, Jane R.; Kinzie, Mable B.; Farace, Elana

    2008-01-01

    The rapid onset and progression of a brain tumor, cognitive and behavioral changes, and uncertainty surrounding prognosis are issues well known to health practitioners in neuro-oncology. We studied the specific challenges that family caregivers face when caring for patients experiencing the significant neurocognitive and neurobehavioral disorders associated with brain tumors. We selected 25 family caregivers of adult brain tumor patients to represent the brain tumor illness trajectory (crisis, chronic, and terminal phases). Interviews documented caregiving tasks and decision-making and information and support needs. Themes were permitted to emerge from the data in qualitative analysis. We found that the family caregivers in this study provided extraordinary uncompensated care involving significant amounts of time and energy for months or years and requiring the performance of tasks that were often physically, emotionally, socially, or financially demanding. They were constantly challenged to solve problems and make decisions as care needs changed, yet they felt untrained and unprepared as they struggled to adjust to new roles and responsibilities. Because the focus was on the patient, their own needs were neglected. Because caregiver information needs are emergent, they are not always known at the time of a clinic visit. Physicians are frequently unable to address caregiver questions, a situation compounded by time constraints and cultural barriers. We provide specific recommendations for (1) improving the delivery of information; (2) enhancing communication among patients, families, and health care providers; and (3) providing psychosocial support for family caregivers. PMID:17993635

  15. Social Skills Training Interventions: A Promising Approach for Children Treated for Brain Tumors

    ERIC Educational Resources Information Center

    Weinberger, Beverley Slome; Barakat, Lamia P.

    2007-01-01

    As a result of their disease, its treatment, and late effects, children treated for brain tumors are at risk for developing problems in social functioning in terms of social competence and peer acceptance, poor social skills, and social isolation. Despite research suggesting the effectiveness of social skills training interventions in improving…

  16. Interstitial laser thermotherapy: developments in the treatment of small deep-seated brain tumors.

    PubMed

    Menovsky, T; Beek, J F; Roux, F X; Bown, S G

    1996-12-01

    New technical advances have made feasible the utilization of laser to destroy deep-seated brain tumors under real-time monitoring. Experience with interstitial laser thermotherapy (ILTT) in animal and clinical studies has been obtained. These studies are summarized and the future potential of ILTT in neurosurgery is discussed.

  17. 3D Slicer as a Tool for Interactive Brain Tumor Segmentation

    PubMed Central

    Kikinis, Ron; Pieper, Steve

    2014-01-01

    User interaction is required for reliable segmentation of brain tumors in clinical practice and in clinical research. By incorporating current research tools, 3D Slicer provides a set of easy to use interactive tools that can be efficiently used for this purpose. PMID:22255945

  18. Primary brain tumors associated with cerebral aneurysm: report of three cases.

    PubMed

    Suslu, Hikmet Turan; Bozbuga, Mustafa

    2011-01-01

    The primary brain tumors associated with cerebral aneurysms are rare in neurosurgical practice. The present article constitutes an evaluation of the management of coexistent primary brain tumor and cerebral aneurysm. A retrospective study of three cases of primary brain tumor with cerebral aneurysm was performed. We evaluated the complications and clinic outcomes by assessing the clinical and imaging findings. Case 1 presented with a subarachnoid hemorrhage from an aneurysm of the anterior communicating artery, with an incidental left frontal oligodendroglioma. Case 2 presented with chronic headache due to left frontal convexity meningioma, with proximal internal carotid artery aneurysm which was found incidentally during preoperative magnetic resonance angiography. Case 3 was admitted to our hospital complaining of headache, memory disturbance, and weakness in her left lower extremity. Magnetic resonance imaging revealed right frontal lymphoma and an unruptured aneurysm at the left middle cerebral artery. Preoperative magnetic resonance imaging revealed right frontal lymphoma and unruptured left middle cerebral artery. The frequency of primary brain tumor and cerebral aneurysm coexistence is increasing due to improvements in high-resolution imaging. In these complicated cases, the management will differ according to each pathology present, and this is an important problem for a neurosurgeon.

  19. Which drug or drug delivery system can change clinical practice for brain tumor therapy?

    PubMed Central

    Siegal, Tali

    2013-01-01

    The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanisms lead to drug failure because of inability to reach the desired target at a sufficient concentration. This perspective reviews the leading strategies that aim to improve drug delivery to brain tumors and their likelihood to change clinical practice. The English literature was searched for defined search items. Strategies that use systemic delivery and those that use local delivery are critically reviewed. In addition, challenges posed for drug delivery by combined treatment with anti-angiogenic therapy are outlined. To impact clinical practice and to achieve more than just a limited local control, new drugs and delivery systems must adhere to basic clinical expectations. These include, in addition to an antitumor effect, a verified favorable adverse effects profile, easy introduction into clinical practice, feasibility of repeated or continuous administration, and compatibility of the drug or delivery system with any tumor size and brain location. PMID:23502426

  20. MIF Maintains the Tumorigenic Capacity of Brain Tumor-Initiating Cells by Directly Inhibiting p53.

    PubMed

    Fukaya, Raita; Ohta, Shigeki; Yaguchi, Tomonori; Matsuzaki, Yumi; Sugihara, Eiji; Okano, Hideyuki; Saya, Hideyuki; Kawakami, Yutaka; Kawase, Takeshi; Yoshida, Kazunari; Toda, Masahiro

    2016-05-01

    Tumor-initiating cells thought to drive brain cancer are embedded in a complex heterogeneous histology. In this study, we isolated primary cells from 21 human brain tumor specimens to establish cell lines with high tumorigenic potential and to identify the molecules enabling this capability. The morphology, sphere-forming ability upon expansion, and differentiation potential of all cell lines were indistinguishable in vitro However, testing for tumorigenicity revealed two distinct cell types, brain tumor-initiating cells (BTIC) and non-BTIC. We found that macrophage migration inhibitory factor (MIF) was highly expressed in BTIC compared with non-BTIC. MIF bound directly to both wild-type and mutant p53 but regulated p53-dependent cell growth by different mechanisms, depending on glioma cell line and p53 status. MIF physically interacted with wild-type p53 in the nucleus and inhibited its transcription-dependent functions. In contrast, MIF bound to mutant p53 in the cytoplasm and abrogated transcription-independent induction of apoptosis. Furthermore, MIF knockdown inhibited BTIC-induced tumor formation in a mouse xenograft model, leading to increased overall survival. Collectively, our findings suggest that MIF regulates BTIC function through direct, intracellular inhibition of p53, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant brain cells. Cancer Res; 76(9); 2813-23. ©2016 AACR. PMID:26980763

  1. Rapid Detection of high-level oncogene amplifications in ultrasonic surgical aspirations of brain tumors

    PubMed Central

    2012-01-01

    Background Genomic tumor information, such as identification of amplified oncogenes, can be used to plan treatment. The two sources of a brain tumor that are commonly available include formalin-fixed, paraffin-embedded (FFPE) sections from the small diagnostic biopsy and the ultrasonic surgical aspiration that contains the bulk of the tumor. In research centers, frozen tissue of a brain tumor may also be available. This study compared ultrasonic surgical aspiration and FFPE specimens from the same brain tumors for retrieval of DNA and molecular assessment of amplified oncogenes. Methods Surgical aspirations were centrifuged to separate erythrocytes from the tumor cells that predominantly formed large, overlying buffy coats. These were sampled to harvest nuclear pellets for DNA purification. Four glioblastomas, 2 lung carcinoma metastases, and an ependymoma were tested. An inexpensive PCR technique, multiplex ligation-dependent probe amplification (MLPA), quantified 79 oncogenes using 3 kits. Copy number (CN) results were normalized to DNA from non-neoplastic brain (NB) in calculated ratios, [tumor DNA]/[NB DNA]. Bland-Altman and Spearman rank correlative comparisons were determined. Regression analysis identified outliers. Results Purification of DNA from ultrasonic surgical aspirations was rapid (<3 days) versus FFPE (weeks) and yielded greater amounts in 6 of 7 tumors. Gene amplifications up to 15-fold corresponded closely between ultrasonic aspiration and FFPE assays in Bland-Altman analysis. Correlation coefficients ranged from 0.71 to 0.99 using 3 kit assays per tumor. Although normalized CN ratios greater than 2.0 were more numerous in FFPE specimens, some were found only in the ultrasonic surgical aspirations, consistent with tumor heterogeneity. Additionally, CN ratios revealed 9 high-level (≥ 6.0) gene amplifications in FFPE of which 8 were also detected in the ultrasonic aspirations at increased levels. The ultrasonic aspiration levels of these

  2. 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

  3. Immune factors and viral interactions in brain cancer etiology and outcomes, The 2016 Brain Tumor Epidemiology Consortium Meeting report.

    PubMed

    Johnson, Kimberly J; Hainfellner, Johannes A; Lau, Ching C; Scheurer, Michael E; Woehrer, Adelheid; Wiemels, Joseph

    2016-01-01

    The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium that aims to advance development of multicenter and interdisciplinary collaborations that focus on research related to the etiology, outcomes, and prevention of brain tumors. The 17th annual BTEC meeting was held in Barcelona, Spain on June 21 - 23, 2016. The meeting focused on immune and viral factors that influence brain tumor development. Fundamentals of innate and adaptive immunity were reviewed, the role of immune checkpoint inhibitors in primary and secondary brain tumors was addressed, vaccination strategies for glioma treatment were presented, and the potential contribution of immune dysfunction and viruses tropic for glial cells in gliomagenesis was discussed. Further contributions addressed the risk of non-ionizing radiation, molecular and birth characteristics on brain tumor induction/outcomes, and patterns of care and effects of different treatments on brain tumor survival in the real world setting. The next BTEC meeting will be held in June 2017 in Banff, Canada, and will focus on brain tumor epidemiology in the era of precision medicine.
. PMID:27546018

  4. 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.

  5. Brain tumor segmentation in MR slices using improved GrowCut algorithm

    NASA Astrophysics Data System (ADS)

    Ji, Chunhong; Yu, Jinhua; Wang, Yuanyuan; Chen, Liang; Shi, Zhifeng; Mao, Ying

    2015-12-01

    The detection of brain tumor from MR images is very significant for medical diagnosis and treatment. However, the existing methods are mostly based on manual or semiautomatic segmentation which are awkward when dealing with a large amount of MR slices. In this paper, a new fully automatic method for the segmentation of brain tumors in MR slices is presented. Based on the hypothesis of the symmetric brain structure, the method improves the interactive GrowCut algorithm by further using the bounding box algorithm in the pre-processing step. More importantly, local reflectional symmetry is used to make up the deficiency of the bounding box method. After segmentation, 3D tumor image is reconstructed. We evaluate the accuracy of the proposed method on MR slices with synthetic tumors and actual clinical MR images. Result of the proposed method is compared with the actual position of simulated 3D tumor qualitatively and quantitatively. In addition, our automatic method produces equivalent performance as manual segmentation and the interactive GrowCut with manual interference while providing fully automatic segmentation.

  6. Microendoscopic Removal of Deep-Seated Brain Tumors Using Tubular Retraction System.

    PubMed

    Ratre, Shailendra; Yadav, Yad Ram; Parihar, Vijay Singh; Kher, Yatin

    2016-07-01

    Background Retraction of the overlying brain can be difficult without causing significant trauma when using traditional brain retractors with blades. These retractors may produce focal pressure and may result in brain contusion or infarction. Tubular retractors offer the advantage of low retracting pressure that is less likely to be traumatic. Low retraction pressure in the tubular retractor is due to the distribution of retraction force in all directions in a larger area. Material and Methods We conducted a retrospective study of 100 patients with deep-seated tumors operated on from January 2010 to December 2014. Tumor removal was accomplished with the help of a microscope and/or endoscope. Tubular brain retractors sizes 23, 18, and 15 mm were used. Folding of the tubular retractor after making a longitudinal cut allowed a small corticectomy. Larger retractor sizes were used in the earlier part of the study and in larger tumors. All the patients were evaluated postoperatively by computed tomography scan on the first postoperative day, and subsequent scans were done as and when needed. Any brain contusion or infarctions and the amount of tumor removal were recorded. Results A total of 74 patients had astrocytomas; 12, meningiomas; 4, colloid cyst of the third ventricle; 4, metastases; 4, primitive neuroectodermal tumor; 1, neurocytoma; and 1, ependymoma. Pure endoscopic excision without using a microscope was performed in 12 patients. Lesions were in the frontal (n = 34), parietal (n = 22), intraventricular (n = 16), basal ganglion or thalamic (n = 14), occipital (n = 10), and cerebellar (n = 4) areas. Total, near-total, and partial excision was achieved in 49, 29, and 22 patients, respectively. Use of a conventional retractor for excision of peripheral and superficial parts of a large tumor, small brain contusions, and technical failure were observed in 7, 4, and 1 patient, respectively. The low incidence of contusion may be partly

  7. Targeted Delivery of Drugs to Brain Tumors (LBNL Summer Lecture Series)

    SciTech Connect

    Forte, Trudy

    2007-06-27

    Summer Lecture Series 2007: Trudy Forte of Berkeley Lab's Life Sciences Division will discuss her work developing nano-sized low-density lipoprotein (LDL) particles that can be used as a safe and effective means of delivering anticancer drugs to brain tumors, particularly glioblastoma multiforme. This is the most common malignant brain tumor in adults and one of the deadliest forms of cancer. Her research team found that the synthetic LDL particles can target and kill such tumors cells in vitro. The nanoparticles are composed of a lipid core surrounded by a peptide. The peptide contains an amino acid sequence that recognizes the LDL receptor, and the lipid core has the ability to accumulate anti-cancer drugs.

  8. Is the Blood-Brain Barrier Relevant in Metastatic Germ Cell Tumor?

    SciTech Connect

    Azar, Jose M. Schneider, Bryan P.; Einhorn, Lawrence H.

    2007-09-01

    Purpose: Germ cell tumors are uniquely chemosensitive and curable, even with advanced metastatic disease. Central nervous system recurrence can terminate a complete remission in other chemosensitive tumors, such as small cell lung cancer, because of the blood-brain barrier (BBB). We propose to document that the BBB is also relevant in germ cell tumors despite their dramatic chemosensitivity. Methods and Materials: We present five cases illustrating the concept of the BBB in patients with metastatic testicular cancer treated with chemotherapy. Results: In our large series of patients with metastatic testicular cancer treated with chemotherapy, we identified 5 unique patients. These patients were rendered free of disease only to experience relapse in the brain alone. This included 1 patient who initially had good-risk metastatic disease by means of the International Germ Cell Collaborative Group staging system at the onset of chemotherapy. Conclusions: The BBB is relevant in patients with metastatic testicular cancer.

  9. 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.

  10. Targeted Delivery of Drugs to Brain Tumors (LBNL Summer Lecture Series)

    ScienceCinema

    Forte, Trudy

    2016-07-12

    Summer Lecture Series 2007: Trudy Forte of Berkeley Lab's Life Sciences Division will discuss her work developing nano-sized low-density lipoprotein (LDL) particles that can be used as a safe and effective means of delivering anticancer drugs to brain tumors, particularly glioblastoma multiforme. This is the most common malignant brain tumor in adults and one of the deadliest forms of cancer. Her research team found that the synthetic LDL particles can target and kill such tumors cells in vitro. The nanoparticles are composed of a lipid core surrounded by a peptide. The peptide contains an amino acid sequence that recognizes the LDL receptor, and the lipid core has the ability to accumulate anti-cancer drugs.

  11. A join point survival model for brain tumor patients.

    PubMed

    Vovoras, Dimitris; Vrionis, Frank D; Tsokos, Chris P; Prokhel, Keshav

    2011-12-01

    To investigate the relationship between medical improvements and the survival experienced by the patient population, it would be useful to find out when and how much the cancer treatment breakthroughs and early diagnosis have significantly improved the prognosis of brain cancer patients. A join point model facilitates the identification of trends with significant change-points in survival; the main goal of such a model would be to find out when cancer survival starts exhibiting a pattern of improvement. The model will be applied to grouped relative survival data for major cancer sites from the 'Surveillance, epidemiology and end results' program of the National Cancer Institute.

  12. 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.

  13. Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients.

    PubMed

    LeBlanc, Amy K; Mazcko, Christina; Brown, Diane E; Koehler, Jennifer W; Miller, Andrew D; Miller, C Ryan; Bentley, R Timothy; Packer, Rebecca A; Breen, Matthew; Boudreau, C Elizabeth; Levine, Jonathan M; Simpson, R Mark; Halsey, Charles; Kisseberth, William; Rossmeisl, John H; Dickinson, Peter J; Fan, Timothy M; Corps, Kara; Aldape, Kenneth; Puduvalli, Vinay; Pluhar, G Elizabeth; Gilbert, Mark R

    2016-09-01

    On September 14-15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed. PMID:27179361

  14. Impacts of Blood-Brain Barrier in Drug Delivery and Targeting of Brain Tumors

    PubMed Central

    Omidi, Yadollah; Barar, Jaleh

    2012-01-01

    Introduction Entry of blood circulating agents into the brain is highly selectively con-trolled by specific transport machineries at the blood brain barrier (BBB), whose excellent barrier restrictiveness make brain drug delivery and targeting very challenging. Methods Essential information on BBB cellular microenvironment were reviewed and discussed towards impacts of BBB on brain drug delivery and targeting. Results Brain capillary endothelial cells (BCECs) form unique biological structure and architecture in association with astrocytes and pericytes, in which microenvironment the BCECs express restrictive tight junctional complexes that block the paracellular inward/outward traverse of biomolecules/compounds. These cells selectively/specifically control the transportation process through carrier and/or receptor mediated transport machineries that can also be exploited for the delivery of pharmaceuticals into the brain. Intelligent molecular therapies should be designed using such transport machineries for the efficient delivery of designated drugs into the brain. For better clinical outcomes, these smart pharmaceuticals should be engineered as seamless nanosystems to provide simultaneous imaging and therapy (multimodal theranostics). Conclusion The exceptional functional presence of BBB selectively controls inward and outward transportation mechanisms, thus advanced smart multifunctional nanomedicines are needed for the effective brain drug delivery and targeting. Fully understanding the biofunctions of BBB appears to be a central step for engineering of intelligent seamless therapeutics consisting of homing device for targeting, imaging moiety for detecting, and stimuli responsive device for on-demand liberation of therapeutic agent. PMID:23678437

  15. 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.

  16. Genetic Contribution of Polymorphisms in Glutathione S-Transferases to Brain Tumor Risk.

    PubMed

    Geng, Peiliang; Li, Jianjun; Wang, Ning; Ou, Juanjuan; Xie, Ganfeng; Sa, Rina; Liu, Chen; Xiang, Lisha; Li, Hongtao; Liang, Houjie

    2016-04-01

    Existing data have shown a major effect of glutathione S-transferase (GST) single-nucleotide polymorphisms on activities of detoxification-related enzymes, and it is the functional importance that leads to extensive research on the association of GST polymorphisms with the risk of developing brain tumor. Previously reported associations, nevertheless, remain inconsistent. This study aimed to reevaluate the association with new information from recent research articles. We weekly searched multiple databases, aiming to cover all studies looking at the associations being examined in this work. Eligibility of studies was evaluated based on predesigned inclusion criteria. To assess the association of GST polymorphisms with brain tumor risk, we calculated genotypic ORs by comparing the number of genotypes between cases and controls. We also detected interstudy heterogeneity, publication bias, and single studies' influence. A total of 13 research articles were identified through databases and hand search. We found significantly elevated risk of brain tumor associated with GSTT1 null status in individuals of European ethnicity (OR 1.46, 95% CI 1.12-1.92). In the analysis of GSTP1 I105V, we observed that Val/Val genotype compared to the Ile/Ile genotype was more prone to a reduced brain tumor risk (OR 0.77, 95% CI 0.64-0.93). Such major effects were similarly seen for GSTP1 A114V (OR 1.14, 95% CI 1.01-1.29 for Val/Val + Ala/Val vs. Ala/Ala). When data were limited to glioma, we found a significant elevation associated with the combination of Val/Val and Ala/Val genotypes (OR 1.18, 95% CI 1.01-1.37). However, no clear association was detected between other polymorphisms investigated and glioma. These statistical data suggest that some of the polymorphisms at GST loci are possibly associated with the genetic risk of brain tumor. PMID:25735248

  17. 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

  18. The transcriptional network for mesenchymal transformation of brain tumors

    PubMed Central

    Carro, Maria Stella; Lim, Wei Keat; Alvarez, Mariano Javier; Bollo, Robert J.; Zhao, Xudong; Snyder, Evan Y.; Sulman, Erik P.; Anne, Sandrine L.; Doetsch, Fiona; Colman, Howard; Lasorella, Anna; Aldape, Ken; Califano, Andrea; Iavarone, Antonio

    2013-01-01

    Inference of transcriptional networks that regulate transitions into physiologic or pathologic cellular states remains a central challenge in systems biology. A mesenchymal phenotype is the hallmark of tumor aggressiveness in human malignant glioma but the regulatory programs responsible for implementing the associated molecular signature are largely unknown. Here, we show that reverse-engineering and unbiased interrogation of a glioma-specific regulatory network reveal the transcriptional module that activates expression of mesenchymal genes in malignant glioma. Two transcription factors (C/EBPβ and Stat3) emerge as synergistic initiators and master regulators of mesenchymal transformation. Ectopic co-expression of C/EBPβ and Stat3 reprograms neural stem cells along the aberrant mesenchymal lineage whereas elimination of the two factors in glioma cells leads to collapse of the mesenchymal signature and reduces tumor aggressiveness. In human glioma, expression of C/EBPβ and Stat3 correlates with mesenchymal differentiation and predicts poor clinical outcome. These results reveal that activation of a small regulatory module is necessary and sufficient to initiate and maintain an aberrant phenotypic state in cancer cells. PMID:20032975

  19. Secondary tics or tourettism associated with a brain tumor.

    PubMed

    Luat, Aimee F; Behen, Michael E; Juhász, Csaba; Sood, Sandeep; Chugani, Harry T

    2009-12-01

    Tourette syndrome is generally considered to be a genetic disorder, but symptoms mimicking Tourette syndrome can be secondary to an underlying lesion disrupting the basal ganglia circuitry. Described here is a case of secondary tics, or tourettism, in a child with a large oligodendroglioma of the right temporal lobe extending to the basal ganglia. He presented with attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and stimulant-induced tic disorder at the age of 11 years, and later also had also seizures. The family history was unremarkable. Cranial magnetic resonance imaging disclosed a right temporal lobe tumor extending to the basal ganglia. An alpha-[(11)C]methyl-l-tryptophan positron emission tomography scan showed asymmetric uptake in the basal ganglia and intense uptake in the tumor. He had a lesionectomy, and the histopathologic diagnosis was oligodendroglioma. Neuropsychologic testing after surgery revealed no attention-deficit hyperactivity disorder symptomatology, and only minimal features of obsessive-compulsive disorder. The present case provides additional evidence supporting the role of basal ganglia circuitry in the pathophysiology of tic disorder and its comorbid states. Children who present with attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic disorder of late onset in the absence of family history should be further investigated with neuroimaging to exclude the presence of a secondary cause.

  20. 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

  1. 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.

  2. Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Recurrent or Refractory Brain Tumors

    ClinicalTrials.gov

    2016-08-03

    Childhood Astrocytoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Diffuse Intrinsic Pontine Glioma; Glioma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Glioblastoma; Recurrent Childhood Medulloblastoma; Recurrent Primitive Neuroectodermal Tumor; Refractory Brain Neoplasm

  3. Near-infrared fluorescence heptamethine carbocyanine dyes mediate imaging and targeted drug delivery for human brain tumor.

    PubMed

    Wu, Jason Boyang; Shi, Changhong; Chu, Gina Chia-Yi; Xu, Qijin; Zhang, Yi; Li, Qinlong; Yu, John S; Zhau, Haiyen E; Chung, Leland W K

    2015-10-01

    Brain tumors and brain metastases are among the deadliest malignancies of all human cancers, largely due to the cellular blood-brain and blood-tumor barriers that limit the delivery of imaging and therapeutic agents from the systemic circulation to tumors. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. Here we identified and synthesized a group of near-infrared fluorescence (NIRF) heptamethine carbocyanine dyes and derivative NIRF dye-drug conjugates for effective imaging and therapeutic targeting of brain tumors of either primary or metastatic origin in mice, which is mechanistically mediated by tumor hypoxia and organic anion-transporting polypeptide genes. We also demonstrate that these dyes, when conjugated to chemotherapeutic agents such as gemcitabine, significantly restricted the growth of both intracranial glioma xenografts and prostate tumor brain metastases and prolonged survival in mice. These results show promise in the application of NIRF dyes as novel theranostic agents for the detection and treatment of brain tumors.

  4. MRI brain tumor segmentation and necrosis detection using adaptive Sobolev snakes

    NASA Astrophysics Data System (ADS)

    Nakhmani, Arie; Kikinis, Ron; Tannenbaum, Allen

    2014-03-01

    Brain tumor segmentation in brain MRI volumes is used in neurosurgical planning and illness staging. It is important to explore the tumor shape and necrosis regions at di erent points of time to evaluate the disease progression. We propose an algorithm for semi-automatic tumor segmentation and necrosis detection. Our algorithm consists of three parts: conversion of MRI volume to a probability space based on the on-line learned model, tumor probability density estimation, and adaptive segmentation in the probability space. We use manually selected acceptance and rejection classes on a single MRI slice to learn the background and foreground statistical models. Then, we propagate this model to all MRI slices to compute the most probable regions of the tumor. Anisotropic 3D di usion is used to estimate the probability density. Finally, the estimated density is segmented by the Sobolev active contour (snake) algorithm to select smoothed regions of the maximum tumor probability. The segmentation approach is robust to noise and not very sensitive to the manual initialization in the volumes tested. Also, it is appropriate for low contrast imagery. The irregular necrosis regions are detected by using the outliers of the probability distribution inside the segmented region. The necrosis regions of small width are removed due to a high probability of noisy measurements. The MRI volume segmentation results obtained by our algorithm are very similar to expert manual segmentation.

  5. A dual neural network ensemble approach for multiclass brain tumor classification.

    PubMed

    Sachdeva, Jainy; Kumar, Vinod; Gupta, Indra; Khandelwal, Niranjan; Ahuja, Chirag Kamal

    2012-11-01

    The present study is conducted to develop an interactive computer aided diagnosis (CAD) system for assisting radiologists in multiclass classification of brain tumors. In this paper, primary brain tumors such as astrocytoma, glioblastoma multiforme, childhood tumor-medulloblastoma, meningioma and secondary tumor-metastases along with normal regions are classified by a dual level neural network ensemble. Two hundred eighteen texture and intensity features are extracted from 856 segmented regions of interest (SROIs) and are taken as input. PCA is used for reduction of dimensionality of the feature space. The study is performed on a diversified dataset of 428 post contrast T1-weighted magnetic resonance images of 55 patients. Two sets of experiments are performed. In the first experiment, random selection is used which may allow SROIs from the same patient having similar characteristics to appear in both training and testing simultaneously. In the second experiment, not even a single SROI from the same patient is common during training and testing. In the first experiment, it is observed that the dual level neural network ensemble has enhanced the overall accuracy to 95.85% compared with 91.97% of single level artificial neural network. The proposed method delivers high accuracy for each class. The accuracy obtained for each class is: astrocytoma 96.29%, glioblastoma multiforme 96.15%, childhood tumor-medulloblastoma 90%, meningioma 93.00%, secondary tumor-metastases 96.67% and normal regions 97.41%. This study reveals that dual level neural network ensemble provides better results than the single level artificial neural network. In the second experiment, overall classification accuracy of 90.4% was achieved. The generalization ability of this approach can be tested by analyzing larger datasets. The extensive training will also further improve the performance of the proposed dual network ensemble. Quantitative results obtained from the proposed method will assist the

  6. Obesity and Risk for Brain/CNS Tumors, Gliomas and Meningiomas: A Meta-Analysis

    PubMed Central

    Sergentanis, Theodoros N.; Tsivgoulis, Georgios; Perlepe, Christina; Ntanasis-Stathopoulos, Ioannis; Tzanninis, Ioannis-Georgios; Sergentanis, Ioannis N.; Psaltopoulou, Theodora

    2015-01-01

    Objective This meta-analysis aims to examine the association between being overweight/obese and risk of meningiomas and gliomas as well as overall brain/central nervous system (CNS) tumors. Study Design Potentially eligible publications were sought in PubMed up to June 30, 2014. Random-effects meta-analysis and dose-response meta-regression analysis was conducted. Cochran Q statistic, I-squared and tau-squared were used for the assessment of between-study heterogeneity. The analysis was performed using Stata/SE version 13 statistical software. Results A total of 22 studies were eligible, namely 14 cohort studies (10,219 incident brain/CNS tumor cases, 1,319 meningioma and 2,418 glioma cases in a total cohort size of 10,143,803 subjects) and eight case-control studies (1,009 brain/CNS cases, 1,977 meningioma cases, 1,265 glioma cases and 8,316 controls). In females, overweight status/obesity was associated with increased risk for overall brain/CNS tumors (pooled RR = 1.12, 95%CI: 1.03–1.21, 10 study arms), meningiomas (pooled RR = 1.27, 95%CI: 1.13–1.43, 16 study arms) and gliomas (pooled RR = 1.17, 95%CI: 1.03–1.32, six arms). Obese (BMI>30 kg/m2) females seemed particularly aggravated in terms of brain/CNS tumor (pooled RR = 1.19, 95%CI: 1.05–1.36, six study arms) and meningioma risk (pooled RR = 1.48, 95%CI: 1.28–1.71, seven arms). In males, overweight/obesity status correlated with increased meningioma risk (pooled RR = 1.58, 95%CI: 1.22–2.04, nine study arms), whereas the respective association with overall brain/CNS tumor or glioma risk was not statistically significant. Dose-response meta-regression analysis further validated the findings. Conclusion Our findings highlight obesity as a risk factor for overall brain/CNS tumors, meningiomas and gliomas among females, as well as for meningiomas among males. PMID:26332834

  7. Brain Tumor Immunotherapy: What have We Learned so Far?

    PubMed Central

    Van Gool, Stefaan Willy

    2015-01-01

    High grade glioma is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy, and chemotherapy. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, we developed an immunotherapy schedule and we categorized patients into clinically defined risk profiles. We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients. The developmental program allows further improvements related to newest scientific insights. Finally, we developed a mode of care within academic centers to organize cell-based therapies for experimental clinical trials in a large number of patients. PMID:26137448

  8. The Neuroimaging Center of the Pediatric Brain Tumor Consortium-collaborative neuroimaging in pediatric brain tumor research: a work in progress.

    PubMed

    Poussaint, T Young; Phillips, P C; Vajapeyam, S; Fahey, F H; Robertson, R L; Osganian, S; Ramamurthy, U; Mulkern, R V; Treves, S T; Boyett, J M; Kun, L E

    2007-04-01

    As an essential part of the National Cancer Institute (NCI)-funded Pediatric Brain Tumor Consortium (PBTC), the Neuroimaging Center (NIC) is dedicated to infusing the study of pediatric brain tumors with imaging "best practice" by producing a correlative research plan that 1) resonates with novel therapeutic interventions being developed by the wider PBTC, 2) ensures that every PBTC protocol incorporates an imaging "end point" among its objectives, 3) promotes the widespread implementation of standardized technical protocols for neuroimaging, and 4) facilitates a quality assurance program that complies with the highest standards for image data transfer, diagnostic image quality, and data integrity. To accomplish these specific objectives, the NIC works with the various PBTC sites (10 in all, plus NCI/ National Institute of Neurological Diseases and Stroke representation) to ensure that the overarching mission of the consortium--to better understand tumor biology and develop new therapies for central nervous system tumors in children--is furthered by creating a uniform body of imaging techniques, technical protocols, and standards. Since the inception of the NIC in 2003, this broader mandate has been largely accomplished through a series of site visits and meetings aimed at assessing prevailing neuroimaging practices against NIC-recommended protocols, techniques, and strategies for achieving superior image quality and executing the secure transfer of data to the central PBTC. These ongoing evaluations periodically examine investigations into targeted drug therapies. In the future, the NIC will concentrate its efforts on improving image analysis for MR imaging and positron-emission tomography (PET) and on developing new ligands for PET; imaging markers for radiation therapy; and novel systemic, intrathecal, and intralesional therapeutic interventions.

  9. Brain tumor resection guided by fluorescence imaging and MRI image guidance

    NASA Astrophysics Data System (ADS)

    Valdes, Pablo; Harris, Brent T.; Leblond, Frederic; Fontaine, Kathryn M.; Ji, Songbai; Pogue, Brian W.; Hartov, Alex; Roberts, David W.; Paulsen, Keith D.

    2009-02-01

    Recent evidence suggests a correlation between extent of tumor resection and patient prognosis, making maximal tumor resection a clinical ideal for neurosurgeons. Our group is currently undertaking a clinical study using fluorescence-based detection of tumor coupled with a standard 3-D image guidance system to study the effectiveness of fluorescence-based detection in the neurosurgical operating room. For fluorescence-based detection, we used 5-aminolevulinic acid to induce accumulation of protoporphyrin IX in malignant tissues. In this paper, we chose one prototypical, highly fluorescent case of glioblastoma multiforme, a high-grade glioma, to highlight some of the key findings and methodology used in our study of fluorescence-based detection and resection of brain tumors.

  10. Cerebral necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies

    SciTech Connect

    Di Chiro, G.; Oldfield, E.; Wright, D.C.; De Michele, D.; Katz, D.A.; Patronas, N.J.; Doppman, J.L.; Larson, S.M.; Ito, M.; Kufta, C.V.

    1988-01-01

    Cerebral necrosis after radiotherapy for brain tumors is being recognized as a problem more common than previously estimated. Distinction between this iatrogenic complication and tumor recurrence cannot be made by either CT or MR imaging. By using positron emission tomography (PET) with /sup 18/F-deoxyglucose (FDG) we were able to reach a diagnosis of radiation necrosis, later verified, in 10 of 95 patients referred for the purpose of differentiating tumor recurrence from necrosis. The critical PET-FDG feature was focal hypometabolism in the area of necrosis, which contrasted with the hypermetabolism associated with the residual/recurrent tumor. In addition, four cases of cerebral necrosis after supraophthalmic, intraarterial chemotherapy (BCNU) were studied with the PET-FDG method. The area of chemotherapy damage was also characterized by marked hypometabolism. Histology revealed both similarities and differences between radio- and chemonecrosis.

  11. [RSF model optimization and its application to brain tumor segmentation in MRI].

    PubMed

    Cheng, Zhaoning; Song, Zhijian

    2013-04-01

    Magnetic resonance imaging (MRI) is usually obscure and non-uniform in gray, and the tumors inside are poorly circumscribed, hence the automatic tumor segmentation in MRI is very difficult. Region-scalable fitting (RSF) energy model is a new segmentation approach for some uneven grayscale images. However, the level set formulation (LSF) of RSF model is not suitable for the environment with different grey level distribution inside and outside the intial contour, and the complex intensity environment of MRI always makes it hard to get ideal segmentation results. Therefore, we improved the model by a new LSF and combined it with the mean shift method, which can be helpful for tumor segmentation and has better convergence and target direction. The proposed method has been utilized in a series of studies for real MRI images, and the results showed that it could realize fast, accurate and robust segmentations for brain tumors in MRI, which has great clinical significance. PMID:23858745

  12. 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.

  13. Semiquantitative Analysis Using Thallium-201 SPECT for Differential Diagnosis Between Tumor Recurrence and Radiation Necrosis After Gamma Knife Surgery for Malignant Brain Tumors

    SciTech Connect

    Matsunaga, Shigeo; Shuto, Takashi; Takase, Hajime; Ohtake, Makoto; Tomura, Nagatsuki; Tanaka, Takahiro; Sonoda, Masaki

    2013-01-01

    Purpose: Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography ({sup 201}Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. Methods and Materials: The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of {sup 201}Tl SPECT data used the early ratio (ER) and the delayed ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. Results: A total of 107 tumors were analyzed with {sup 201}Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. Conclusions: Semiquantitative analysis of {sup 201}Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most

  14. Asparagine Depletion Potentiates the Cytotoxic Effect of Chemotherapy Against Brain Tumors

    PubMed Central

    Panosyan, Eduard H.; Wang, Yuntao; Xia, Peng; Lee, Wai-Nang Paul; Pak, Youngju; Laks, Dan R.; Lin, Henry J.; Moore, Theodore B.; Cloughesy, Timothy F.; Kornblum, Harley I.; Lasky, Joseph L.

    2014-01-01

    Targeting amino acid metabolism has therapeutic implications for aggressive brain tumors. Asparagine is an amino acid that is synthesized by normal cells. However, some cancer cells lack asparagine synthetase (ASNS), the key enzyme for asparagine synthesis. Asparaginase (ASNase) contributes to eradication of acute leukemia by decreasing asparagine levels in serum and cerebrospinal fluid. However, leukemic cells may become ASNase-resistant by up-regulating ASNS. High expression of ASNS has also been associated with biological aggressiveness of other cancers, including gliomas. Here, the impact of enzymatic depletion of asparagine on proliferation of brain tumor cells was determined. ASNase was used as monotherapy or in combination with conventional chemotherapeutic agents. Viability assays for ASNase-treated cells demonstrated significant growth reduction in multiple cell lines. This effect was reversed by glutamine in a dose-dependent manner -- as expected, because glutamine is the main amino group donor for asparagine synthesis. ASNase treatment also reduced sphere formation by medulloblastoma and primary glioblastoma cells. ASNase-resistant glioblastoma cells exhibited elevated levels of ASNS mRNA. ASNase co-treatment significantly enhanced gemcitabine or etoposide cytotoxicity against glioblastoma cells. Xenograft tumors in vivo showed no significant response to ASNase monotherapy and little response to temozolomide (TMZ) alone. However, combinatorial therapy with ASNase and TMZ resulted in significant growth suppression for an extended duration of time. Taken together, these findings indicate that amino acid depletion warrants further investigation as adjunctive therapy for brain tumors. PMID:24505127

  15. Distribution, characterization and significance of polyomavirus genomic sequences in tumors of the brain and its covering.

    PubMed

    Delbue, Serena; Pagani, Elisabetta; Guerini, Franca R; Agliardi, Cristina; Mancuso, Roberta; Borghi, Elisa; Rossi, Francesca; Boldorini, Renzo; Veggiani, Claudia; Car, Pier Giorgio; Ferrante, Pasquale

    2005-11-01

    The etiology of brain tumors and meningiomas is still unknown. Several factors have been considered, such as genetic predisposition and environmental risk factors, but the hypothesis that one or more infectious agents may play a role in tumor pathogenesis has also been investigated. Therefore, emphasis was placed on the neurooncogenic family Polyomaviridae and the presence of human polyomavirus DNA sequences and JCV mRNA were examined in malignant human brain biopsies. Italian patients affected with different types of neoplasias of the brain and its covering were enrolled. The patients underwent surgical tumor excision and the presence of the polyomavirus genome in biopsy and other body fluids was evaluated by PCR. In addition, the genomic organization of JCV was examined in depth, with the aim of providing information on genotype distribution and TCR rearrangements in the population affected with intracranial neoplasms. On the whole, polyomavirus DNA was found in 50% of the biopsy specimens studied, JC virus DNA and BK virus DNA were amplified in 40.6% mainly glioblastomas and 9.4% of the tissue specimens, respectively, while none of the biopsy specimens tested contained Simian virus 40 DNA. Genotype 1 and Mad 4 TCR organization were the most frequent in the population enrolled. Although a cause and effect was not demonstrated and the specific role of the viruses remains unknown, the findings appear to confirm the hypothesis that JCV and BKV could be important co-factors in tumor pathogenesis.

  16. Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

    PubMed Central

    Gajjar, Amar; Pfister, Stefan M.; Taylor, Michael D.; Gilbertson, Richard J.

    2014-01-01

    High-throughput genomic technologies have shed light on the biologic heterogeneity of several pediatric brain tumors. The biology of the four common pediatric brain tumors—namely medulloblastoma, ependymoma, high-grade glioma including diffuse intrinsic pontine glioma and low-grade glioma are highlighted in this CCR Focus article. The discovery that medulloblastoma consists of 4 different subgroups namely WNT, SHH, Group 3 and Group 4, each with distinct clinical and molecular features, has impacted the treatment of children with medulloblastoma. Prospective studies have documented the efficacy of SMO inhibitors in a subgroup of patients with SHH medulloblastoma. Efforts are ongoing to develop specific therapies for each of the subgroups of medulloblastoma. Similar efforts are being pursued for ependymoma, high grade glioma and diffuse intrinsic pontine glioma where the disease outcome for the latter two tumors has not changed over the past 3 decades despite several prospective clinical trials. Developing and testing targeted therapies based on this new understanding remains a major challenge to the pediatric neuro-oncology community. The focus of this review is to summarize the rapidly evolving understanding of the common pediatric brain tumors based on genome wide analysis. These novel insights will add impetus to translating these laboratory based discoveries to newer therapies for children diagnosed with these tumors. PMID:25398846

  17. Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.

    PubMed

    Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

    2015-04-15

    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.

  18. Quantitative analysis of topoisomerase II{alpha} to rapidly evaluate cell proliferation in brain tumors

    SciTech Connect

    Oda, Masashi; Arakawa, Yoshiki; Kano, Hideyuki; Kawabata, Yasuhiro; Katsuki, Takahisa; Shirahata, Mitsuaki; Ono, Makoto; Yamana, Norikazu; Hashimoto, Nobuo; Takahashi, Jun A. . E-mail: jat@kuhp.kyoto-u.ac.jp

    2005-06-17

    Immunohistochemical cell proliferation analyses have come into wide use for evaluation of tumor malignancy. Topoisomerase II{alpha} (topo II{alpha}), an essential nuclear enzyme, has been known to have cell cycle coupled expression. We here show the usefulness of quantitative analysis of topo II{alpha} mRNA to rapidly evaluate cell proliferation in brain tumors. A protocol to quantify topo II{alpha} mRNA was developed with a real-time RT-PCR. It took only 3 h to quantify from a specimen. A total of 28 brain tumors were analyzed, and the level of topo II{alpha} mRNA was significantly correlated with its immuno-staining index (p < 0.0001, r = 0.9077). Furthermore, it sharply detected that topo II{alpha} mRNA decreased in growth-inhibited glioma cell. These results support that topo II{alpha} mRNA may be a good and rapid indicator to evaluate cell proliferate potential in brain tumors.

  19. Thallium-201 brain tumor imaging: a comparative study with pathologic correlation

    SciTech Connect

    Kaplan, W.D.; Takvorian, T.; Morris, J.H.; Rumbaugh, C.L.; Connolly, B.T.; Atkins, H.L.

    1987-01-01

    In patients with gliomas who were stable or improving, we noted a disparity between clinical status and computed tomography (CT) brain scan results. To elucidate this finding, 29 patients were sequentially scanned with 2.0 mCi of /sup 201/Tl (5-30 min), 20 mCi (/sup 99m/Tc)gluceptate (GH) (3-4 hr) and 7-10 mCi 67Ga (48-72 hr). A total of 198 images were obtained. A set of three scans at a midpoint in follow up was selected for analysis. Seven patients who died had neuropathologic data available; brain sections were reconstructed to match radionuclide views without knowledge of image results. In the seven patients with autopsy data, /sup 201/Tl offered the most accurate correlation with viable tumor. Gallium-67 gave similar results in patients not receiving steroids. Technetium-99m GH scans could not allow differentiation between tumor, necrosis, and edema. Similarly, the CT scan could not routinely differentiate between fibrotic, nonfibrotic, necrotic, and neoplastic tissue. In the 22 patients without autopsy data, /sup 201/Tl scans commonly showed smaller and more focal abnormal uptake when compared with (/sup 99m/Tc)GH and /sup 67/Ga scans. Thallium-201 scans more accurately reflect viable tumor burden than other radionuclide studies of primary brain tumors, are minimally affected by concomitant steroid administration, can be performed immediately following tracer administration, and complement the anatomic data obtained from CT scans.

  20. Atlas-based segmentation of brain tumor images using a Markov random field-based tumor growth model and non-rigid registration.

    PubMed

    Bauer, Stefan; Seiler, Christof; Bardyn, Thibaut; Buechler, Philippe; Reyes, Mauricio

    2010-01-01

    We propose a new and clinically oriented approach to perform atlas-based segmentation of brain tumor images. A mesh-free method is used to model tumor-induced soft tissue deformations in a healthy brain atlas image with subsequent registration of the modified atlas to a pathologic patient image. The atlas is seeded with a tumor position prior and tumor growth simulating the tumor mass effect is performed with the aim of improving the registration accuracy in case of patients with space-occupying lesions. We perform tests on 2D axial slices of five different patient data sets and show that the approach gives good results for the segmentation of white matter, grey matter, cerebrospinal fluid and the tumor.

  1. Brain tumor demarcation with liquid-crystal tunable filter spectral imaging

    NASA Astrophysics Data System (ADS)

    Gebhart, Steven C.; Mahadevan-Jansen, Anita

    2006-02-01

    Past studies have demonstrated that combined fluorescence and diffuse reflectance spectroscopy can successfully discriminate between normal, tumor core, and tumor margin tissues in the brain. To achieve efficient surgical resection guidance with optical biopsy, probe-based spectroscopy must be extended to spectral imaging to spatially demarcate the tumor margins. This paper describes the design and testing of a combined fluorescence and diffuse reflectance imaging system which uses liquid-crystal tunable filter technology. Experiments were conducted to quantitatively determine its linearity, field of view, spatial and spectral resolution, and wavelength sensitivity. For functional testing, spectral images were acquired from tissue phantoms, mouse brain in vitro, and rat brain cortex in vivo. The spectral imaging system is characterized by measured intensities which are linear with sample emission intensity and integration time, a one-inch field of view for a seven-inch object distance, spectral resolution which is linear with wavelength, spatial resolution which is pixel-limited, and sensitivity functions which provide a guide for the distribution of total image integration time between wavelengths. Functional testing demonstrated good spatial and spectral constrast between brain tissue types, the capability to acquire adequate fluorescence and diffuse reflectance intensities within a one-minute imaging timeframe, and the importance of hemostasis to acquired signal strengths and imaging speed.

  2. Suicide ideation in pediatric and adult survivors of childhood brain tumors.

    PubMed

    Brinkman, Tara M; Liptak, Cori C; Delaney, Brian L; Chordas, Christine A; Muriel, Anna C; Manley, Peter E

    2013-07-01

    Survivors of pediatric brain tumors are at risk for long-term psychological morbidities. The current study investigated the prevalence and predictors of suicide ideation (SI) in a clinical sample of youth and adult survivors. Retrospective chart reviews were completed for 319 survivors of pediatric brain tumors who were assessed via clinical interview during routine neuro-oncology clinic visits between 2003 and 2007. Survivors were, on average, 18.0 years of age (SD = 4.9) and 10 years from diagnosis (SD = 5.0) at their most recent follow-up. The most common diagnosis was low-grade glioma (n = 162) followed by embryonal tumors (PNET/medulloblastoma; n = 64). Multivariable logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) for SI. Nearly 12 % of survivors (11.7 %, n = 37) reported SI. Five survivors (1.5 %) had documented suicide attempts, though none were fatal. In a multivariable model, adjusting for sex and age, history of depression (OR = 20.6, 95 % CI = 4.2-101.1), psychoactive medication treatment (OR = 4.5, 95 % CI = 1.8-11.2), observation or surgery only treatment (OR = 3.7, 95 % CI = 1.5-9.1), and seizures (OR = 3.6, 95 % CI = 1.1-11.1) were significantly associated with SI in survivors. Survivors of pediatric brain tumors appear to be at risk for experiencing SI. Our results underscore the importance of a multidisciplinary approach to providing follow-up care for childhood brain tumor survivors, including routine psychological screenings.

  3. Chemotherapy for brain tumors of astrocytic and oligodendroglial lineage: the past decade and where we are heading.

    PubMed Central

    Levin, V. A.

    1999-01-01

    Over the past three decades, we have made great strides in the treatment of most, but not all, brain tumors. Dramatic advances have occurred in diagnostic imaging, neurosurgery, neuroanesthesia, radiotherapy, and chemotherapy for CNS tumors. Unfortunately, our progress has not yet met our expectations. Because of the infiltrative nature of most primary brain tumors, neurosurgery can never be expected to be curative for the majority of gliomas. Because infiltrative tumors interdigitate with normal brain cells and are not highly sensitive to irradiation, one cannot expect radiotherapy to be curative without serious damage to normal brain cells. The hope for a cure, then, rests with chemotherapy. Those who administer chemotherapy to patients with CNS tumors fully expect that, in time, long-term survival and, ultimately, the cure will become an everyday reality. To achieve that reality, however, new treatment concepts and drugs are needed. PMID:11550304

  4. Tl-201 and Tc-99m-Sestamibi SPECT for brain tumor detection: Comparison using MRI coregistration

    SciTech Connect

    Darcourt, J.; Itti, L.; Chang, L.

    1994-05-01

    Tl-201 (Tl) brain SPECT has been validated for the differential diagnosis of high versus low grade gliomas and recurrence versus radiation necrosis. We compared this technique to Tc-99m-Sestamibi (MIBI) SPECT in 9 patients (pts) with brain tumors using MRI coregistration. Pts were injected with 4 mCi of Tl and brain SPECT was performed using a dedicated brain system. This was immediately following by an injection of 20 mCi of MIBI and a brain SPECT using the same camera and with the pt in the same position. Four pts were studied for the diagnosis of radiation necrosis vs. tumor recurrence (2 had biopsy proven recurrence); 5 pts were studied for primary tumor evaluation: 2 meningiomas, 1 oligodendroglioma, 1 low-grade astrocytoma, 1 cysticercosis. Coregistration was performed for every pt by 3D surface fitting of the inner skull MIBI contour to the MRI brain surface extracted automatically. ROIs were drawn on the MRI and applied to the coregistered MIBI and Tl images for tumor to non-tumor ratios T/NT calculations. There was a tight correlation between MIBI and Tl T/NT (r-0.96) and a 1.5 threshold separated radiation necrosis from recurrence and low from high grade primary tumors. Therefore, the data already available on Tl brain tumor imaging can be used with MIBI SPECT with the advantage of a better image quality (2.5 to 4 times more counts).

  5. Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus.

    PubMed

    Todo, T; Rabkin, S D; Sundaresan, P; Wu, A; Meehan, K R; Herscowitz, H B; Martuza, R L

    1999-11-20

    Replication-competent, attenuated herpes simplex virus (HSV) vectors have been developed for viral oncolytic therapy of primary and metastatic malignant brain tumors. However, the role of the host immune responses in the brain has not been elucidated. N18 neuroblastoma cells were used as a tumor model in syngeneic A/J mice to test the therapeutic efficacy of G207, a conditionally replicating HSV vector, in an immunocompetent condition. G207 inoculated intraneoplastically exhibited a prominent oncolytic antitumor effect in mice harboring N18 tumors in the brain or subcutaneously, and, in addition, elicited a systemic antitumor immune response. Subcutaneous tumor therapy with G207 caused regression of a remote, established tumor in the brain or in the periphery, which was potentially mediated by the systemic antitumor immune response, and provided persistent tumor-specific protection against N18 tumor rechallenge in the brain as well as in the periphery. Antitumor immunity was associated with an elevation of specific CTL activity against N18 tumor cells that persisted for at least 13 months. The results suggest that the oncolytic antitumor action of replication-competent HSV may be augmented by induction of specific and systemic antitumor immunity effective both in the periphery and in the brain.

  6. Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

  7. Was Julius Caesar's epilepsy due to a brain tumor?

    PubMed

    Gomez, J G; Kotler, J A; Long, J B

    1995-03-01

    Two thousand thirty-eight years later, in the setting of a similar care presentation, a physician would take a detailed history and perform a clinical and neurological examination. A preliminary diagnosis would be entertained and followed by electroencephalography and magnetic resonance of the brain with and without paramagnetic contrast for diagnostic confirmation. The proper medical or surgical treatment would then be instituted. A reconstruction of the clinical history of Julius Caesar (100-44 B.C.) has been attempted from available information from literature. Although a definite conclusion obviously cannot be made, a differential diagnosis provided with a tentative hypothesis is presented. The patient had late onset of seizures in the last two years of his life, headaches, personality changes. Upon reexamination of existing Julius Caesar iconography, busts, statues and minted coins no skull deformities have been noted. Identification of a skull deformity as described by Suetonius would have confirmed the suspicion of meningioma involving the convexity of the cerebral hemispheres. Meningioma or slow-growing supratentorial glioma may well have been responsible for this man's illness. Who knows how the course of history might have been changed... Probably not at all. PMID:7738524

  8. Magnetic resonance-guided laser interstitial thermal therapy: report of a series of pediatric brain tumors.

    PubMed

    Tovar-Spinoza, Zulma; Choi, Hoon

    2016-06-01

    OBJECTIVE Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel, minimally invasive treatment that has multiple advantages in pediatric use and broad applicability for different types of lesions. Here, the authors report the preliminary results of the first series of pediatric brain tumors treated with MRgLITT at Golisano Children's Hospital in Syracuse, New York. METHODS Pediatric brain tumors treated with MRgLITT between February 2012 and August 2014 at Golisano Children's Hospital were evaluated retrospectively. Medical records, radiological findings, surgical data, complications, and results of tumor volumetric analyses were reviewed. The Visualase thermal laser system (Medtronic) was used in all MRgLITT procedures. RESULTS This series included 11 patients with 12 tumors (pilocytic astrocytoma, ependymoma, medulloblastoma, choroid plexus xanthogranuloma, subependymal giant cell astrocytoma, and ganglioglioma). A single laser and multiple overlapping ablations were used for all procedures. The mean laser dose was 10.23 W, and the mean total ablation time was 68.95 seconds. The mean initial target volume was 6.79 cm(3), and the mean immediate post-ablation volume was 7.86 cm(3). The mean hospital stay was 3.25 days, and the mean follow-up time was 24.5 months. Tumor volume decreased in the first 3 months after surgery (n = 11; p = 0.007) and continued to decrease by the 4- to 6-month followup (n = 11; mean volume 2.61 cm(3); p = 0.009). Two patients experienced post-ablation complications: transient right leg weakness in one patient, and transient hemiparesis, akinetic mutism, and eye movement disorder in the other. CONCLUSIONS Magnetic resonance-guided laser interstitial thermal therapy is an effective first- or second-line treatment for select pediatric brain tumors. Larger multiinstitutional clinical trials are necessary to evaluate its use for different types of lesions to further standardize practices.

  9. Magnetic resonance-guided laser interstitial thermal therapy: report of a series of pediatric brain tumors.

    PubMed

    Tovar-Spinoza, Zulma; Choi, Hoon

    2016-06-01

    OBJECTIVE Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel, minimally invasive treatment that has multiple advantages in pediatric use and broad applicability for different types of lesions. Here, the authors report the preliminary results of the first series of pediatric brain tumors treated with MRgLITT at Golisano Children's Hospital in Syracuse, New York. METHODS Pediatric brain tumors treated with MRgLITT between February 2012 and August 2014 at Golisano Children's Hospital were evaluated retrospectively. Medical records, radiological findings, surgical data, complications, and results of tumor volumetric analyses were reviewed. The Visualase thermal laser system (Medtronic) was used in all MRgLITT procedures. RESULTS This series included 11 patients with 12 tumors (pilocytic astrocytoma, ependymoma, medulloblastoma, choroid plexus xanthogranuloma, subependymal giant cell astrocytoma, and ganglioglioma). A single laser and multiple overlapping ablations were used for all procedures. The mean laser dose was 10.23 W, and the mean total ablation time was 68.95 seconds. The mean initial target volume was 6.79 cm(3), and the mean immediate post-ablation volume was 7.86 cm(3). The mean hospital stay was 3.25 days, and the mean follow-up time was 24.5 months. Tumor volume decreased in the first 3 months after surgery (n = 11; p = 0.007) and continued to decrease by the 4- to 6-month followup (n = 11; mean volume 2.61 cm(3); p = 0.009). Two patients experienced post-ablation complications: transient right leg weakness in one patient, and transient hemiparesis, akinetic mutism, and eye movement disorder in the other. CONCLUSIONS Magnetic resonance-guided laser interstitial thermal therapy is an effective first- or second-line treatment for select pediatric brain tumors. Larger multiinstitutional clinical trials are necessary to evaluate its use for different types of lesions to further standardize practices. PMID:26849811

  10. Evaluation of Technetium-99m glucoheptonate single photon emission computed tomography for brain tumor grading

    PubMed Central

    Alam, Syed Shafiq; Junaid, Syed; Ahmed, Syed Mushtaq

    2016-01-01

    Background: This study is designed to appraise the diagnostic value of technetium-99m glucoheptonate (Tc-99m GHA) single photon emission computed tomography (SPECT) in brain tumor grading. Subjects and Methods: The study was performed on 30 patients referred from the Department of Neurosurgery, who were from both urban and rural areas. Data were collected through interview, history taking, and clinical examination followed by recording the desired parameters and finally imaging. The study subjects were divided into five groups: Controls (n = 4), low-grade tumors (n = 8), high-grade tumors (n = 8), metastases (n = 5), and nonneoplastic lesions (n = 5). This division was based on the World Health Organization (WHO) classification postclinico-histological diagnosis. Each of the subjects underwent contrast-enhanced computed tomography/contrast-enhanced magnetic resonance and Tc-99m GHA SPECT preoperatively. All were followed up postoperatively, and histopathological reports were regarded as the gold standard for tumor grading wherever available. Results: It was found that high-grade tumors (Grades III/IV and IV/IV according to the WHO classification) showed significantly higher tumor to normal (T/N) ratios as well as Tmax/N ratios when compared with low-grade tumors (Grades I/IV and II/IV), metastases or nonneoplastic lesions. Conclusions: In summary, the results of this study suggest that in situations where a preoperative grading of tumor is required Tc-99m GHA can be used in tumor grading and its use should be encouraged. Semi-quantitative analysis using both T/N as well as Tmax/N can be used in differentiating high-grade tumors from low-grade ones. PMID:27057217

  11. Antitumor efficacy and intratumoral distribution of SN-38 from polymeric depots in brain tumor model

    PubMed Central

    Vejjasilpa, Ketpat; Manaspon, Chawan; Larbcharoensub, Noppadol; Boongird, Atthaporn; Hongeng, Suradej; Israsena, Nipan

    2015-01-01

    We investigate antitumor efficacy and 2D and 3D intratumoral distribution of 7-ethyl-10-hydroxycamptothecin (SN-38) from polymeric depots inside U-87MG xenograft tumor model in nude mice. Results showed that polymeric depots could be used to administer and controlled release of a large amount of SN-38 directly to the brain tumor model. SN-38 released from depots suppressed tumor growth, where the extent of suppression greatly depended on doses and the number of depot injections. Tumor suppression of SN-38 from depots was three-fold higher in animals which received double injections of depots at high dose (9.7 mg of SN-38) compared to single injection (2.2 mg). H&E staining of tumor sections showed that the area of tumor cell death/survival of the former group was two-fold higher than those of the latter group. Fluorescence imaging based on self-fluorescent property of SN-38 was used to evaluate the intratumoral distribution of this drug compared to histological results. The linear correlation between fluorescence intensity and the amount of SN-38 allowed quantitative determination of SN-38 in tumor tissues. Results clearly showed direct correlation between the amount of SN-38 in tumor sections and cancer cell death. Moreover, 3D reconstruction representing the distribution of SN-38 in tumors was obtained. Results from this study suggest the rationale for intratumoral drug administration and release of drugs inside tumor, which is necessary to design drug delivery systems with efficient antitumor activity. PMID:26080460

  12. The role and clinical significance of DNA damage response and repair pathways in primary brain tumors

    PubMed Central

    2013-01-01

    Primary brain tumors, in particular, glioblastoma multiforme (GBM), continue to have dismal survivability despite advances in treating other neoplasms. The goal of new anti-glioma therapy development is to increase their therapeutic ratios by enhancing tumor control and/or decreasing the severity and incidence of side effects. Because radiotherapy and most chemotherapy agents rely on DNA damage, the cell’s DNA damage repair and response (DRR) pathways may hold the key to new therapeutic strategies. DNA double-strand breaks (DSBs) generated by ionizing radiation and chemotherapeutic agents are the most lethal form of damage, and are repaired via either homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways. Understanding and exploitation of the differences in the use of these repair pathways between tumor and normal brain cells will allow for an increase in tumor cell killing and decreased normal tissue damage. A literature review and discussion on new strategies which can improve the anti-glioma therapeutic ratio by differentially targeting HR and NHEJ function in tumor and normal neuronal tissues is the focus of this article. PMID:23388100

  13. Statistical Validation of Brain Tumor Shape Approximation via Spherical Harmonics for Image-Guided Neurosurgery1

    PubMed Central

    Goldberg-Zimring, Daniel; Talos, Ion-Florin; Bhagwat, Jui G.; Haker, Steven J.; Black, Peter M.; Zou, Kelly H.

    2005-01-01

    Rationale and Objectives Surgical planning now routinely uses both two-dimensional (2D) and three-dimensional (3D) models that integrate data from multiple imaging modalities, each highlighting one or more aspects of morphology or function. We performed a preliminary evaluation of the use of spherical harmonics (SH) in approximating the 3D shape and estimating the volume of brain tumors of varying characteristics. Materials and Methods Magnetic resonance (MR) images from five patients with brain tumors were selected randomly from our MR-guided neurosurgical practice. Standardized mean square reconstruction errors (SMSRE) by tumor volume were measured. Validation metrics for comparing performances of the SH method against segmented contours (SC) were the dice similarity coefficient (DSC) and standardized Euclidean distance (SED) measure. Results Tumor volume range was 22413–85189 mm3, and range of number of vertices in triangulated models was 3674–6544. At SH approximations with degree of at least 30, SMSRE were within 1.66 × 10−5 mm−1. Summary measures yielded a DSC range of 0.89–0.99 (pooled median, 0.97 and significantly >0.7; P < .001) and an SED range of 0.0002–0.0028 (pooled median, 0.0005). Conclusion 3D shapes of tumors may be approximated by using SH for neurosurgical applications. PMID:15831419

  14. 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.

  15. Metabolic studies and neurotoxicity in tumors and brain of mice after hypoxic cell sensitizers

    SciTech Connect

    Streffer, C.; Tamulevicius, P. )

    1994-06-15

    The effects of the radiosensitizers RK-28 and RP-170, both 2-nitroimidazole nucleoside analogues, and KU-2285, a fluorinated 2-nitroimidazole, as well as etanidazole (ETA) on glucose metabolism in mouse tumors and brain were studied to assess their degree of neurotoxicity. Adult male C57B1 mice received differing doses of the above sensitizers IP. Blood, brain, and tumor samples were removed at various times and the levels of glycolytic metabolites determined. Glucose uptake and phosphorylation in brain were measured by the 2-deoxyglucose method of Sokoloff et al. RP-170 showed neither signs of toxicity nor significant alterations in glucose metabolism in brain or tumor at doses up to 4 g/kg b.w. up to 4 h. By contrast, RK-28 was extremely neurotoxic at a dose of 1 g/kg b.w. with a high degree of lethality, resulting in a highly significant increase in the brain glucose level from 0.38 [mu]mol/g to 2.20 [mu]mol/g 2 h after administration, whereas that in the tumor was decreased. KU-2285 and ETA were significantly less toxic than RK-28 at this dose, as reflected in a lower increase in the brain glucose level (0.60 [mu]mol/g), although KU-2285 approaches that of RK-28 (1.43 [mu]mol/g) after 2 h following a dose of 2 g/kg b.w. However, in contrast to the other sensitizers, KU-2285 concomitantly also resulted in a highly significant continuous increase in tumor glucose levels. Labeled [sup 3]H-2deoxyglucose studies showed that RP-170 neither markedly affected the uptake of total radioactivity into the brain nor its degree of phosphorylation whereas, KU-2285 (2 g/kg) and RK-28 (1 g/kg) decreased uptake by [approximately]50% and phosphorylation approximately 3 and 4-fold, respectively. At doses of 1 g/kg, ETA and KU-2285 showed no significant changes in these parameters. This indicates a decreased level of neurotoxicity. 9 refs., 1 fig., 5 tabs.

  16. 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.

  17. 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

  18. 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.

  19. Clustering of brain tumor cells: a first step for understanding tumor recurrence

    NASA Astrophysics Data System (ADS)

    Khain, Evgeniy; Nowicki, M. O.; Chiocca, E. A.; Lawler, S. E.; Schneider-Mizell, C. M.; Sander, L. M.

    2012-02-01

    Glioblastoma tumors are highly invasive; therefore the overall prognosis of patients remains poor, despite major improvements in treatment techniques. Cancer cells detach from the inner tumor core and actively migrate away [1]; eventually these invasive cells might form clusters, which can develop to recurrent tumors. In vitro experiments in collagen gel [1] followed the clustering dynamics of different glioma cell lines. Based on the experimental data, we formulated a stochastic model for cell dynamics, which identified two mechanisms of clustering. First, there is a critical value of the strength of adhesion; above the threshold, large clusters grow from a homogeneous suspension of cells; below it, the system remains homogeneous, similarly to the ordinary phase separation. Second, when cells form a cluster, there is evidence that their proliferation rate increases. We confirmed the theoretical predictions in a separate cell migration experiment on a substrate and found that both mechanisms are crucial for cluster formation and growth [2]. In addition to their medical importance, these phenomena present exciting examples of pattern formation and collective cell behavior in intrinsically non-equilibrium systems [3]. [4pt] [1] A. M. Stein et al, Biophys. J., 92, 356 (2007). [0pt] [2] E. Khain et al, EPL 88, 28006 (2009). [0pt] [3] E. Khain et al, Phys. Rev. E. 83, 031920 (2011).

  20. The role of computed tomography in the diagnosis and management of brain tumors

    SciTech Connect

    Salazar, O.M.; VanHoutte, P.; Plassche, W.M. Jr.; Keller, B.E.

    1981-01-01

    This review article emphasizes the role of computed tomography in the diagnosis and management of brain tumors. The head CT scan has become one of the most precise noninvasive tests in the neurosciences. It has given clinicians more information than they were able to obtain in the past. The subject is covered by subdividing it into several categories: detection of true tumor extent, radiation treatment planning, the immediate postoperative period, treatment responses, failure patterns, detection of radiation-induced damage, and the potential to predict histopathology. The paper is illustrated with examples that emphasize the advantages and some of the limitations of computed tomography as it exists today.

  1. [Utility of hyperbaric oxygenation in radiotherapy for malignant brain tumors--a literature review].

    PubMed

    Beppu, Takaaki; Tanaka, Katsuyuki; Kohshi, Kiyotaka

    2009-06-01

    Over the past 50 years, hyperbaric oxygenation (HBO) therapy has been used in a wide variety of medical conditions; this theraphy causes an increase in oxygen tension in blood and tissues. In the treatment of malignant gliomas, HBO therapy is used for the radiosensitization of cells in combination with radiotherapy (RT). Further, HBO therapy is applied for the treatment and prevention of radiation-induced brain necrosis that is the most serious complication observed after radiosurgery. We reviewed the literature to evaluate the manner in which HBO therapy contributes to clinical fields in cases of RT administration for malignant brain tumors.

  2. 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

  3. Epidemiology of Primary Brain Tumors in the Middle Eastern Population in California, 2001–2005

    PubMed Central

    Nasseri, Kiumarss; Mills, John R.

    2009-01-01

    Background The fast growing Middle Eastern (ME) population has rarely been studied in the US. The purpose of this study was to compare the epidemiology of primary brain tumors in this ethnic population with the non-Hispanic, non-Middle Eastern White (NHNMW) in California. Methods ME cases were identified by surname in the California cancer registry and ME population estimates were based on ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant, 16 uncertain) in the ME and 15,589 cases (8,352 benign, 6,812 malignant, 425 uncertain) in the NHNMW were available for this study. Results ME patients were significantly (p<0.05) younger and their age-adjusted incidence rates per 100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than similar rates of 7.3 and 10.6 in the NHNMW group (p<0.05). Rates for malignant tumors were similar. Meningioma was the main histology responsible for the observed increase in patients over 40 years of age. Also increased were benign tumors of the pituitary and pineal glands. The overall mortality in patients with benign tumors was significantly lower than malignant tumors. Conclusions This study presents a significantly high incidence of benign meningioma in the ME population in California. This may be due to higher susceptibility or exposure of this ethnic group to the risk factor(s) for this neoplasm. Considering the reported causal association of benign meningioma with childhood radiation exposure from Israel, exposure to this risk factor in this ethnic group needs to be evaluated in future studies. PMID:19588542

  4. Brain MRI Tumor Detection using Active Contour Model and Local Image Fitting Energy

    NASA Astrophysics Data System (ADS)

    Nabizadeh, Nooshin; John, Nigel

    2014-03-01

    Automatic abnormality detection in Magnetic Resonance Imaging (MRI) is an important issue in many diagnostic and therapeutic applications. Here an automatic brain tumor detection method is introduced that uses T1-weighted images and K. Zhang et. al.'s active contour model driven by local image fitting (LIF) energy. Local image fitting energy obtains the local image information, which enables the algorithm to segment images with intensity inhomogeneities. Advantage of this method is that the LIF energy functional has less computational complexity than the local binary fitting (LBF) energy functional; moreover, it maintains the sub-pixel accuracy and boundary regularization properties. In Zhang's algorithm, a new level set method based on Gaussian filtering is used to implement the variational formulation, which is not only vigorous to prevent the energy functional from being trapped into local minimum, but also effective in keeping the level set function regular. Experiments show that the proposed method achieves high accuracy brain tumor segmentation results.

  5. Evaluation of image quality of MRI data for brain tumor surgery

    NASA Astrophysics Data System (ADS)

    Heckel, Frank; Arlt, Felix; Geisler, Benjamin; Zidowitz, Stephan; Neumuth, Thomas

    2016-03-01

    3D medical images are important components of modern medicine. Their usefulness for the physician depends on their quality, though. Only high-quality images allow accurate and reproducible diagnosis and appropriate support during treatment. We have analyzed 202 MRI images for brain tumor surgery in a retrospective study. Both an experienced neurosurgeon and an experienced neuroradiologist rated each available image with respect to its role in the clinical workflow, its suitability for this specific role, various image quality characteristics, and imaging artifacts. Our results show that MRI data acquired for brain tumor surgery does not always fulfill the required quality standards and that there is a significant disagreement between the surgeon and the radiologist, with the surgeon being more critical. Noise, resolution, as well as the coverage of anatomical structures were the most important criteria for the surgeon, while the radiologist was mainly disturbed by motion artifacts.

  6. Semi-autonomous Simulated Brain Tumor Ablation with RavenII Surgical Robot using Behavior Tree

    PubMed Central

    Hu, Danying; Gong, Yuanzheng; Hannaford, Blake; Seibel, Eric J.

    2015-01-01

    Medical robots have been widely used to assist surgeons to carry out dexterous surgical tasks via various ways. Most of the tasks require surgeon’s operation directly or indirectly. Certain level of autonomy in robotic surgery could not only free the surgeon from some tedious repetitive tasks, but also utilize the advantages of robot: high dexterity and accuracy. This paper presents a semi-autonomous neurosurgical procedure of brain tumor ablation using RAVEN Surgical Robot and stereo visual feedback. By integrating with the behavior tree framework, the whole surgical task is modeled flexibly and intelligently as nodes and leaves of a behavior tree. This paper provides three contributions mainly: (1) describing the brain tumor ablation as an ideal candidate for autonomous robotic surgery, (2) modeling and implementing the semi-autonomous surgical task using behavior tree framework, and (3) designing an experimental simulated ablation task for feasibility study and robot performance analysis. PMID:26405563

  7. Hematoporphyrin-derivative photodynamic in-vitro sensitivity testing for brain tumors

    NASA Astrophysics Data System (ADS)

    Plattner, Michael; Bernwick, Walter; Kostron, Herwig

    1993-03-01

    Brain tumors of various histologies were subjected to an in-vitro photodynamic-sensitivity test. The studies were performed on primary cultures of human glioblastomas, meningiomas, and ependymomas, which were exposed to increasing concentrations of hematoporphyrin derivative and 60 J/cm2 delivered by an argon-dye laser at 632 nm. A growth inhibition of 75% was demonstrated at a concentration of 25 (mu) g and 10 (mu) g HPD/ml medium for two different glioblastomas, respectively. A growth inhibition of 75% was observed in the ependymoma line at 10 and 50 (mu) g HPD/ml with and without light, respectively. The meningioma demonstrated a 75% inhibition already at (mu) g and 75 (mu) g/ml medium with and without light, respectively. These results demonstrate a significant difference in the response of brain tumors to photodynamic treatment (PDT). In vitro-PDT-assay should be taken into account if clinical application of PDT is considered.

  8. Fluorescein Sodium-Guided Surgery of Malignant Brain Tumors: History, Current Concepts, and Future Project.

    PubMed

    Schebesch, Karl-Michael; Brawanski, Alexander; Hohenberger, Christoph; Hohne, Julius

    2016-01-01

    Fluorescein sodium (FL)-guided resection has become an important and beneficial treatment method for malignant brain tumors. FL-guided resection improves the rate of gross total resection in high-grade gliomas (HGG) and cerebral metastases (CM). FL sensitively visualizes the disruption of the blood-brain barrier in the area surrounding malignant lesions, similar to contrast-enhanced T1-weighted MR sequences. This review of the current literature summarizes the history of FL in neurosurgery from 1946 until today. We discuss the molecular mechanism of FL accumulation in cerebral malignant tumors and provide an overview of the current practice of using FL and applying a dedicated surgical microscope filter. Additionally, we outline and discuss ongoing trials and future projects. PMID:26956810

  9. 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.

  10. Evaluation of the increase in permeability of the blood–brain barrier during tumor progression after pulsed focused ultrasound

    PubMed Central

    Yang, Feng-Yi; Wang, Hsin-Ell; Lin, Guan-Liang; Lin, Hui-Hsien; Wong, Tai-Tong

    2012-01-01

    Purpose The purpose of this study was to evaluate the permeability of the blood–brain barrier after sonication by pulsed high-intensity focused ultrasound and to determine if such an approach increases the tumor:ipsilateral brain permeability ratio. Materials and methods F98 glioma-bearing Fischer 344 rats were injected intravenously with Evans blue with or without blood–tumor barrier disruption induced by transcranial pulsed high-intensity focused ultrasound. Sonication was applied at a frequency of 1 MHz with a 5% duty cycle and a repetition frequency of 1 Hz. The permeability of the blood–brain barrier was assessed by the extravasation of Evans blue. Contrast-enhanced magnetic resonance images were used to monitor the gadolinium deposition path associated with transcranial pulsed high-intensity focused ultrasound, and the influencing size and location was also investigated. In addition, whole brain histological analysis was performed. The results were compared by two-tailed unpaired t-test. Results The accumulation of Evans blue in brains and the tumor:ipsilateral brain permeability ratio of Evans blue were significantly increased after pulsed high-intensity focused ultrasound exposure. Evans blue injection followed by sonication showed an increase in the tumor:ipsilateral brain ratio of the target tumors (9.14:1) of about 2.23-fold compared with the control tumors (x4.09) on day 6 after tumor implantation. Magnetic resonance images showed that pulsed high-intensity focused ultrasound locally enhances the permeability of the blood–tumor barrier in the glioma-bearing rats. Conclusion This method could allow enhanced synergistic effects with respect to other brain tumor treatment regimens. PMID:22359451

  11. The Long and Winding Road: from the high affinity choline uptake site to clinical trials for malignant brain tumors

    PubMed Central

    Lowenstein, Pedro R.; Castro, Maria G.

    2016-01-01

    Malignant brain tumors are one of the most lethal cancers. They originate from glial cells and invade throughout the brain. Current standard of care involves surgical resection, radiotherapy and chemotherapy, and median survival is currently ~14–20 months post-diagnosis. Glioma tumors are highly infiltrative. Given that the brain immune system is deficient in priming systemic immune responses to glioma antigens present within the brain, we proposed to reconstitute the brain immune system to achieve immunological priming from within the brain. Two adenoviral vectors are injected into the resection cavity or remaining tumor. One adenoviral vector expresses the HSV-1 derived thymidine kinase which converts ganciclovir into a compound only cytotoxic to dividing glioma cells. The second adenovirus expresses the cytokine fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L differentiates precursors into dendritic cells and acts as a chemokine for dendritic cells. HSV-1/ganciclovir killing of tumor cells releases tumor antigens that are taken up by dendritic cells within the brain tumor microenvironment. Tumor killing also releases HMGB1, a TLR2 agonist that activates dendritic cells. HMGB1 activated dendritic cells, loaded with glioma antigens, migrate to cervical lymph nodes to stimulate a systemic CD8+ T cells cytotoxic immune response against glioma. This immune response is specific to glioma tumors, induces immunological memory, and does neither cause brain toxicity nor autoimmune responses. An IND was granted by the FDA on 4/7/2011. A Phase I, first in person, to test whether re-engineering the brain immune system is potentially therapeutic is ongoing. PMID:27288077

  12. Association between number of cell phone contracts and brain tumor incidence in nineteen U.S. States.

    PubMed

    Lehrer, Steven; Green, Sheryl; Stock, Richard G

    2011-02-01

    Some concern has arisen about adverse health effects of cell phones, especially the possibility that the low power microwave-frequency signal transmitted by the antennas on handsets might cause brain tumors or accelerate the growth of subclinical tumors. We analyzed data from the Statistical Report: Primary Brain Tumors in the United States, 2000-2004 and 2007 cell phone subscription data from the Governing State and Local Sourcebook. There was a significant correlation between number of cell phone subscriptions and brain tumors in nineteen US states (r = 0.950, P < 0.001). Because increased numbers of both cell phone subscriptions and brain tumors could be due solely to the fact that some states, such as New York, have much larger populations than other states, such as North Dakota, multiple linear regression was performed with number of brain tumors as the dependent variable, cell phone subscriptions, population, mean family income and mean age as independent variables. The effect of cell phone subscriptions was significant (P = 0.017), and independent of the effect of mean family income (P = 0.894), population (P = 0.003) and age (0.499). The very linear relationship between cell phone usage and brain tumor incidence is disturbing and certainly needs further epidemiological evaluation. In the meantime, it would be prudent to limit exposure to all sources of electro-magnetic radiation.

  13. Clair Engle and the brain tumor that almost derailed the Civil Rights Act.

    PubMed

    Son, Colin

    2015-07-01

    Senator Clare Engle was a United States senator from California who cast an important vote to end the filibuster of the 1964 Civil Rights Act, even as a brain tumor had left him with an expressive aphasia and would claim his life just a month later. This paper reviews the history of Senator Engle's illness in parallel with that of the Civil Rights Act of 1964.

  14. The clinical impact of SPECT/PET co-registration with MRI in patients with brain tumors

    SciTech Connect

    Macapinlac, H.A.; Scott, A.M.; Zhang, J.J.

    1994-05-01

    We wanted to evaluate the clinical impact of co-registering SPECT and PET images with MRI (Gd-DTPA) in brain tumor patients. 81 patients with known or suspected brain tumors had 168 SPECT and/or PET scans which were difficult to interpret were coregistered with MRI. A modified Pellizari/Chen surface matching algorithm was used to fit the SPECT/PET and MR images. Impact of the technique on interpretation of the scans was defined as (A) no effect, (B) moderate effect (better localize abnormal uptake to suspected tumor and distinguish normal activity from tumor), (C) basis for final interpretation (distinguish tumor from necrosis, localize biopsy site, find occult tumor, grading of tumor). Impact on patient management was defined as (A) no effect, (B) altered diagnostic/treatment decision (continuation of conservative care, or justify chemo or radiation), (C) basis for treatment (direct biopsy, surgery, and/or radiation).

  15. Optimizing brain tumor resection. Midfield interventional MR imaging.

    PubMed

    Alexander, E

    2001-11-01

    The development of the intraoperative MR imager represents an important example of creative vision and interdisciplinary teamwork. The result is a remarkable tool for neurosurgical applications. MRT allows surgical manipulation under direct visualization of the intracranial contents through the eye of the surgeon and through the volumetric images of the MR imaging system. This technology can be applied to cranial and spinal cases, and forseeably can encompass application to the entire gamut of neurosurgical efforts. The author's experience has been that this device is easy and comfortable for the surgeon to use. Image acquisition, giving views in the plane of choice, lasts no more than 2 to 60 seconds (depending on the imaging method), and does not increase the duration of a given procedure substantially. The author believes that the information received through intraoperative MR imaging scanning ultimately will contribute to decreasing the duration of surgery. Future possibilities include combining the intraoperative MR imager with other technologies, such as the endoscope, focused ultrasound, robotics, and the evaluation of brain function intraoperatively. The development of the intraoperative MR imager marks a significant advance in neurosurgery, an advance that will revolutionize intraoperative visualization as fully as the operating microscope. The combination of intraoperative visualization and precise surgical navigation is unparalleled, and its enhancement of surgical applications will be widespread. Considering the remarkable potential of the intraoperative MR imager for neurosurgical applications, optimal magnet design, image quality, and navigational methods are necessary to capitalize on the advantages of this revolutionary tool. The intraoperative MR imaging system that the author's team has developed and used has combined these features, and allows the performance of open surgical procedures without the need of patient or magnet repositioning. By

  16. 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

  17. Memoirs of an amnesiac--two years with brain cancer, or the outer space of living with brain tumors.

    PubMed Central

    Dor-Ner, A. D.

    1991-01-01

    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

  18. 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.

  19. 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

    2012-04-15

    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.

  20. 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.

  1. 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

  2. A Brain Tumor Molecular Imaging Strategy Using A New Triple-Modality MRI-Photoacoustic-Raman Nanoparticle

    PubMed Central

    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

    2011-01-01

    The vexing difficulty in delineating brain tumor margins represents a major obstacle toward better outcome of brain tumor patients. 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 – surface enhanced Raman scattering (SERS) nanoparticle (MPR) can accurately help delineate the margins of brain tumors in living mice both pre- and intra-operatively. The MPRs were detected by all three modalities with at least picomolar sensitivity both in vitro and in living mice. Intravenous injection of MPRs into glioblastoma-bearing mice led to specific MPR accumulation and retention by the tumors, allowing for non-invasive tumor delineation by all three modalities through the intact skull. Raman imaging allowed guidance of intra-operative tumor resection, and histological correlation validated that Raman imaging is accurately delineating brain tumor margins. This novel triple-modality nanoparticle approach holds promise to enable more accurate brain tumor imaging and resection. PMID:22504484

  3. Melanotic neuroectodermal tumor of the brain recurring 12 years after complete remission: case report.

    PubMed

    Omodaka, Shunsuke; Saito, Ryuta; Kumabe, Toshihiro; Kawagishi, Jun; Jokura, Hidefumi; Sonoda, Yukihiko; Watanabe, Mika; Kayama, Takamasa; Tominaga, Teiji

    2010-04-01

    We describe a rare case of melanotic neuroectodermal tumor (MNT) of the brain recurring 12 years after complete remission. An 11-year-old girl initially presented with exotropia and bilateral papilledema. Magnetic resonance (MR) imaging revealed an intracranial extraaxial large tumor at the midfrontal region. T(1)-weighted MR imaging showed the tumor to be well delineated with homogeneous enhancement by gadolinium. The tumor was subtotally removed, and the histological diagnosis was MNT. The residual tumor became enlarged, so gamma knife radiosurgery was performed 5 months after initial surgery. The enhanced lesion disappeared, but another lesion emerged 3 years later. A second gamma knife radiosurgery was performed for this local recurrence. The enhanced lesion disappeared once again. Twelve years after the second gamma knife radiosurgery, another local recurrence was detected. This tumor was subtotally removed. Histological examination confirmed the same diagnosis of MNT. This case suggests that MNTs not completely resected need long-term follow up, even if complete remission was achieved after adjuvant therapy.

  4. Small unilamellar vesicles: a platform technology for molecular imaging of brain tumors

    NASA Astrophysics Data System (ADS)

    Iqbal, Umar; Albaghdadi, Homam; Nieh, Mu-Ping; Tuor, Ursula I.; Mester, Zoltan; Stanimirovic, Danica; Katsaras, John; Abulrob, Abedelnasser

    2011-05-01

    Molecular imaging enables the non-invasive investigation of cellular and molecular processes. Although there are challenges to overcome, the development of targeted contrast agents to increase the sensitivity of molecular imaging techniques is essential for their clinical translation. In this study, spontaneously forming, small unilamellar vesicles (sULVs) (30 nm diameter) were used as a platform to build a bimodal (i.e., optical and magnetic resonance imaging (MRI)) targeted contrast agent for the molecular imaging of brain tumors. sULVs were loaded with a gadolinium (Gd) chelated lipid (Gd-DPTA-BOA), functionalized with targeting antibodies (anti-EGFR monoclonal and anti-IGFBP7 single domain), and incorporated a near infrared dye (Cy5.5). The resultant sULVs were characterized in vitro using small angle neutron scattering (SANS), phantom MRI and dynamic light scattering (DLS). Antibody targeted and nontargeted Gd loaded sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice using time domain optical imaging and MRI. The results demonstrated that a spontaneously forming, nanosized ULVs loaded with a high payload of Gd can selectively target and image, using MR and optical imaging, brain tumor vessels when functionalized with anti-IGFBP7 single domain antibodies. The unique features of these targeted sULVs make them promising molecular MRI contrast agents.

  5. Small Unilamellar Vesicles: A Platform Technology for Molecular Imaging of Brain Tumors

    SciTech Connect

    Iqbal, U; Albaghdadi, H; Nieh, Mu-Ping; Tuor, U.I; Mester, Z; Stanimirovic, D; Katsaras, John; Abulrob, A

    2011-01-01

    Molecular imaging enables the non-invasive investigation of cellular and molecular processes. Although there are challenges to overcome, the development of targeted contrast agents to increase the sensitivity of molecular imaging techniques is essential for their clinical translation. In this study, spontaneously forming, small unilamellar vesicles (sULVs) (30 nm diameter) were used as a platform to build a bimodal (i.e., optical and magnetic resonance imaging (MRI)) targeted contrast agent for the molecular imaging of brain tumors. sULVs were loaded with a gadolinium (Gd) chelated lipid (Gd-DPTA-BOA), functionalized with targeting antibodies (anti-EGFR monoclonal and anti-IGFBP7 single domain), and incorporated a near infrared dye (Cy5.5). The resultant sULVs were characterized in vitro using small angle neutron scattering (SANS), phantom MRI and dynamic light scattering (DLS). Antibody targeted and nontargeted Gd loaded sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice using time domain optical imaging and MRI. The results demonstrated that a spontaneously forming, nanosized ULVs loaded with a high payload of Gd can selectively target and image, using MR and optical imaging, brain tumor vessels when functionalized with anti-IGFBP7 single domain antibodies. The unique features of these targeted sULVs make them promising molecular MRI contrast agents.

  6. Small unilamellar vesicles: a platform technology for molecular imaging of brain tumors.

    PubMed

    Iqbal, Umar; Albaghdadi, Homam; Nieh, Mu-Ping; Tuor, Ursula I; Mester, Zoltan; Stanimirovic, Danica; Katsaras, John; Abulrob, Abedelnasser

    2011-05-13

    Molecular imaging enables the non-invasive investigation of cellular and molecular processes. Although there are challenges to overcome, the development of targeted contrast agent