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Sample records for brain tumor perfusion

  1. Visual analysis of longitudinal brain tumor perfusion

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  2. 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

  3. 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

  4. Comparison of Perfusion- and Diffusion-weighted Imaging Parameters in Brain Tumor Studies Processed Using Different Software Platforms

    PubMed Central

    Milchenko, Mikhail V.; Rajderkar, Dhanashree; LaMontagne, Pamela; Massoumzadeh, Parinaz; Bogdasarian, Ronald; Schweitzer, Gordon; Benzinger, Tammie; Marcus, Dan; Shimony, Joshua S.; Fouke, Sarah Jost

    2015-01-01

    Rationale and Objectives To compare quantitative imaging parameter measures from diffusion- and perfusion-weighted imaging magnetic resonance imaging (MRI) sequences in subjects with brain tumors that have been processed with different software platforms. Materials and Methods Scans from 20 subjects with primary brain tumors were selected from the Comprehensive Neuro-oncology Data Repository at Washington University School of Medicine (WUSM) and the Swedish Neuroscience Institute. MR images were coregistered, and each subject's data set was processed by three software packages: 1) vendor-specific scanner software, 2) research software developed at WUSM, and 3) a commercially available, Food and Drug Administration–approved, processing platform (Nordic Ice). Regions of interest (ROIs) were chosen within the brain tumor and normal nontumor tissue. The results obtained using these methods were compared. Results For diffusion parameters, including mean diffusivity and fractional anisotropy, concordance was high when comparing different processing methods. For perfusion-imaging parameters, a significant variance in cerebral blood volume, cerebral blood flow, and mean transit time (MTT) values was seen when comparing the same raw data processed using different software platforms. Correlation was better with larger ROIs (radii ≥ 5 mm). Greatest variance was observed in MTT. Conclusions Diffusion parameter values were consistent across different software processing platforms. Perfusion parameter values were more variable and were influenced by the software used. Variation in the MTT was especially large suggesting that MTT estimation may be unreliable in tumor tissues using current MRI perfusion methods. PMID:25088833

  5. [Brain MR perfusion and MR spectroscopy in differentiation of radiation necrosis from tumor recurrence (case report)].

    PubMed

    Tekşam, Mehmet; Kayahan, Esra Meltem; Yerli, Hasan; Ağildere, A Muhteşem

    2004-12-01

    It is not always possible to differentiate tumor recurrence from radiation necrosis using conventional MR images. In this report we present a case of pathologically proven radiation necrosis which appeared as nodular contrast enhancement on conventional MR images in a patient who was surgically treated for grade II astrocytoma 5 years ago. There were decreased choline, creatine and N-acetyl aspartate peaks and significantly increased lipid peak on multivoxel H1-MR spectroscopy while there was no significant perfusion increase on MR perfusion. These findings suggested changes secondary to radiation necrosis. PMID:15611913

  6. 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 ...

  7. Brain Tumors

    MedlinePlus

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

  8. Brain tumors.

    PubMed Central

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

    1991-01-01

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

  9. 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

  10. Brain tumor - primary - adults

    MedlinePlus

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

  11. Brain tumor - children

    MedlinePlus

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

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ( ...

  16. Metastatic brain tumor

    MedlinePlus

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

  17. Adolescent and Pediatric Brain Tumors

    MedlinePlus

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

  18. 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 ...

  19. Evaluation of CT Perfusion Biomarkers of Tumor Hypoxia

    PubMed Central

    Qi, Qi; Yeung, Timothy Pok Chi; Lee, Ting-Yim; Bauman, Glenn; Crukley, Cathie; Morrison, Laura; Hoffman, Lisa; Yartsev, Slav

    2016-01-01

    Background Tumor hypoxia is associated with treatment resistance to cancer therapies. Hypoxia can be investigated by immunohistopathologic methods but such procedure is invasive. A non-invasive method to interrogate tumor hypoxia is an attractive option as such method can provide information before, during, and after treatment for personalized therapies. Our study evaluated the correlations between computed tomography (CT) perfusion parameters and immunohistopathologic measurement of tumor hypoxia. Methods Wistar rats, 18 controls and 19 treated with stereotactic radiosurgery (SRS), implanted with the C6 glioma tumor were imaged using CT perfusion on average every five days to monitor tumor growth. A final CT perfusion scan and the brain were obtained on average 14 days (8–22 days) after tumor implantation. Tumor hypoxia was detected immunohistopathologically with pimonidazole. The tumor, necrotic, and pimonidazole-positive areas on histology samples were measured. Percent necrotic area and percent hypoxic areas were calculated. Tumor volume (TV), blood flow (BF), blood volume (BV), and permeability-surface area product (PS) were obtained from the CT perfusion studies. Correlations between CT perfusion parameters and histological parameters were assessed by Spearman’s ρ correlation. A Bonferroni-corrected P value < 0.05 was considered significant. Results BF and BV showed significant correlations with percent hypoxic area ρ = -0.88, P < 0.001 and ρ = -0.81, P < 0.001, respectively, for control animals and ρ = -0.7, P < 0.001 and ρ = -0.6, P = 0.003, respectively, for all animals, while TV and BV were correlated (ρ = -0.64, P = 0.01 and ρ = -0.43, P = 0.043, respectively) with percent necrotic area. PS was not correlated with either percent necrotic or percent hypoxic areas. Conclusions Percent hypoxic area provided significant correlations with BF and BV, suggesting that CT perfusion parameters are potential non-invasive imaging biomarkers of tumor

  20. Metastatic brain tumor

    MedlinePlus

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

  1. 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 ...

  2. Early perfusion changes in patients with recurrent high-grade brain tumor treated with Bevacizumab: preliminary results by a quantitative evaluation

    PubMed Central

    2012-01-01

    Background To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by a Perfusion Computed Tomography (PCT), may be a predictor of the response to treatment assessed through conventional MRI follow-up. Methods Sixteen patients were enrolled in the present study. For each patient, two PCT examinations, before and after the first dose of bevacizumab, were acquired. Areas of abnormal Cerebral Blood Volume (CBV) were manually defined on the CBV maps, using co-registered T1- weighted images, acquired before treatment, as a guide to the tumor location. Different perfusion metrics were derived from the histogram analysis of the normalized CBV (nCBV) maps; both hyper and hypo-perfused sub-volumes were quantified in the lesion, including tumor necrosis. A two-tailed Wilcoxon test was used to establish the significance of changes in the different perfusion metrics, observed at baseline and during treatment. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated. Results Significant reductions in mean and median nCBV were detected throughout the entire patient population, after only a single dose of bevacizumab. The nCBV histogram modifications indicated the normalization effect of bevacizumab on the tumor abnormal vasculature. An improvement in hypoxia after a single dose of bevacizumab was predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up. Conclusions These preliminary results show that a quantification of changes in necrotic intra-tumoral regions could be proposed as a potential imaging biomarker of tumor response to anti-VEGF therapies. PMID:22494770

  3. Central Nervous System Lymphoma in a 3-Year-Old Male Suffering from a Severe Juvenile Xanthogranuloma – the Usefulness of Perfusion Weighted Imaging and Diffusion Weighted Imaging in the Diagnostics of Pediatric Brain Tumors

    PubMed Central

    Neska-Matuszewska, Małgorzata; Zimny, Anna; Kałwak, Krzysztof; Sąsiadek, Marek J.

    2015-01-01

    Summary Background Primary Central Nervous System Lymphomas (PCNSLs) are rare, malignant brain tumors derived from lymphocytes B. Juvenile xanthogranuloma (JXG) is a non-Langerhans histiocytic cell disorder in children which mostly affects the skin. Rare fatalities have been reported in extracutaneous manifestation. Brain magnetic resonance imaging (MRI) is a method of choice in the diagnostics of all neoplastic CNS lesions. Perfusion weighted imaging (PWI) and diffusion weighted imaging (DWI) allow for more detailed analysis of brain tumors including the rate of neoangiogenesis and cellularity. We presented a pediatric patient suffering from JXG with CNS involvement and the role of brain MRI including DWI and PWI in the evaluation of brain focal lesions. Case Report A 3-year-old male with severe JXG underwent two stem cell transplantations with a development of neurological complications. The patient underwent emergency CT and MRI which revealed a non-specific enhancing focal brain lesion. In DWI it showed restricted diffusion while PWI revealed low values of rCBV and the signal intensity curve returning above the baseline level. Advanced MRI techniques such as DWI and PWI suggested PCNSL. Stereotactic biopsy confirmed PCNSL due to Ebstein-Barr virus reactivation. Conclusions The use of advanced MRI sequences is important to differentiate brain lesions in pediatric patients. The use of PWI and DWI facilitated the diagnosis of PCNSL. It is important to remember that PCNSLs show a very typical pattern of changes visualized with MRI such as: usually strong homogenous enhancement, restricted diffusion and low perfusion. PMID:25624957

  4. Pediatric Brain Tumor Foundation

    MedlinePlus

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

  5. 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, ...

  6. 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 ...

  7. American Brain Tumor Association

    MedlinePlus

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

  8. 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 ...

  9. Childhood Brain Tumors

    MedlinePlus

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

  10. Perfusion harmonic imaging of the human brain

    NASA Astrophysics Data System (ADS)

    Metzler, Volker H.; Seidel, Guenter; Wiesmann, Martin; Meyer, Karsten; Aach, Til

    2003-05-01

    The fast visualisation of cerebral microcirculation supports diagnosis of acute cerebrovascular diseases. However, the commonly used CT/MRI-based methods are time consuming and, moreover, costly. Therefore we propose an alternative approach to brain perfusion imaging by means of ultrasonography. In spite of the low signal/noise-ratio of transcranial ultrasound and the high impedance of the skull, flow images of cerebral blood flow can be derived by capturing the kinetics of appropriate contrast agents by harmonic ultrasound image sequences. In this paper we propose three different methods for human brain perfusion imaging, each of which yielding flow images indicating the status of the patient's cerebral microcirculation by visualising local flow parameters. Bolus harmonic imaging (BHI) displays the flow kinetics of bolus injections, while replenishment (RHI) and diminution harmonic imaging (DHI) compute flow characteristics from contrast agent continuous infusions. RHI measures the contrast agents kinetics in the influx phase and DHI displays the diminution kinetics of the contrast agent acquired from the decay phase. In clinical studies, BHI- and RHI-parameter images were found to represent comprehensive and reproducible distributions of physiological cerebral blood flow. For DHI it is shown, that bubble destruction and hence perfusion phenomena principally can be displayed. Generally, perfusion harmonic imaging enables reliable and fast bedside imaging of human brain perfusion. Due to its cost efficiency it complements cerebrovascular diagnostics by established CT/MRI-based methods.

  11. Quantification of brain perfusion with tracers retained by the brain

    SciTech Connect

    Pupi, A.; Bacciottini, L.; De Cristofaro, M.T.R.; Formiconi, A.R.; Castagnoli, A.

    1991-12-31

    Almost a decade ago, tracers, labelled with {sup 123}I and {sup 99m}Tc, that are retained by the brain, started to be used for studies of regional brain perfusion (regional cerebral blood flow, rCBF). To date, these tracers have been used for brain perfusion imaging with SPECT in brain disorders as well as for physiological activation protocols. Only seldom, however, have they been used in protocols that quantitatively measure rCBF. Nevertheless, comparative studies with perfusion reference tracers have repeatedly demonstrated that the brain uptake of these brain-retained tracers is correlated to perfusion, the major determinant of the distribution of these tracers in the brain. The brain kinetics of {sup 99m}Tc HMPAO, which is the tracer most commonly used, was described with a two-compartment tissue model. The theoretical approach, which is, in itself, sufficient for modeling quantitative measurements with {sup 99m}Tc HMPAO, initially suggested the possibility of empirically narrowing the distance between the brain`s regional uptake of the tracer and rCBF with a linearization algorithm which uses the cerebellum as the reference region. The value of this empirical method is hampered by the fact that the cerebellum can be involved in cerebrovascular disease (i.e. cerebellar diaschisis) as well as in several other brain disorders (e.g. anxiety, and dementia of the Alzheimer type). It also was proposed that different reference regions (occipital, whole slice, or whole brain) should be selected in relation to the brain disorder under study. However, this approach does not solve the main problem because it does not equip us with a reliable tool to evaluate rCBF with a high predictive value, and, at the same time, to reduce intersubject variability. The solution would be to measure a quantitative parameter which directly reflects rCBF, such as the unidirectional influx constant of the freely diffusible flow-limited tracers. 45 refs., 3 figs., 1 tab.

  12. Brain tumor - children

    MedlinePlus

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

  13. The pediatric template of brain perfusion

    PubMed Central

    Avants, Brian B; Duda, Jeffrey T; Kilroy, Emily; Krasileva, Kate; Jann, Kay; Kandel, Benjamin T; Tustison, Nicholas J; Yan, Lirong; Jog, Mayank; Smith, Robert; Wang, Yi; Dapretto, Mirella; Wang, Danny J J

    2015-01-01

    Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7–18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development. PMID:25977810

  14. 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

  15. Epilepsy and brain tumors.

    PubMed

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

    2016-01-01

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

  16. Ultrasound perfusion signal processing for tumor detection

    NASA Astrophysics Data System (ADS)

    Kim, MinWoo; Abbey, Craig K.; Insana, Michael F.

    2016-04-01

    Enhanced blood perfusion in a tissue mass is an indication of neo-vascularity and a sign of a potential malignancy. Ultrasonic pulsed-Doppler imaging is a preferred modality for noninvasive monitoring of blood flow. However, the weak blood echoes and disorganized slow flow make it difficult to detect perfusion using standard methods without the expense and risk of contrast enhancement. Our research measures the efficiency of conventional power-Doppler (PD) methods at discriminating flow states by comparing measurement performance to that of an ideal discriminator. ROC analysis applied to the experimental results shows that power Doppler methods are just 30-50 % efficient at perfusion flows less than 1ml/min, suggesting an opportunity to improve perfusion assessment through signal processing. A new perfusion estimator is proposed by extending the statistical discriminator approach. We show that 2-D perfusion color imaging may be enhanced using this approach.

  17. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

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

  18. Aquaporins and Brain Tumors.

    PubMed

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

    2016-01-01

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

  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. Brain Tumor Risk Factors

    MedlinePlus

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

  1. Living with a Brain Tumor

    MedlinePlus

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

  2. 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) ...

  3. 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

  4. Automatic brain tumor segmentation

    NASA Astrophysics Data System (ADS)

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

    1998-06-01

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

  5. ASFNR recommendations for clinical performance of MR dynamic susceptibility contrast perfusion imaging of the brain.

    PubMed

    Welker, K; Boxerman, J; Kalnin, A; Kaufmann, T; Shiroishi, M; Wintermark, M

    2015-06-01

    MR perfusion imaging is becoming an increasingly common means of evaluating a variety of cerebral pathologies, including tumors and ischemia. In particular, there has been great interest in the use of MR perfusion imaging for both assessing brain tumor grade and for monitoring for tumor recurrence in previously treated patients. Of the various techniques devised for evaluating cerebral perfusion imaging, the dynamic susceptibility contrast method has been employed most widely among clinical MR imaging practitioners. However, when implementing DSC MR perfusion imaging in a contemporary radiology practice, a neuroradiologist is confronted with a large number of decisions. These include choices surrounding appropriate patient selection, scan-acquisition parameters, data-postprocessing methods, image interpretation, and reporting. Throughout the imaging literature, there is conflicting advice on these issues. In an effort to provide guidance to neuroradiologists struggling to implement DSC perfusion imaging in their MR imaging practice, the Clinical Practice Committee of the American Society of Functional Neuroradiology has provided the following recommendations. This guidance is based on review of the literature coupled with the practice experience of the authors. While the ASFNR acknowledges that alternate means of carrying out DSC perfusion imaging may yield clinically acceptable results, the following recommendations should provide a framework for achieving routine success in this complicated-but-rewarding aspect of neuroradiology MR imaging practice. PMID:25907520

  6. {sup 99m}Tc radiopharmaceuticals for brain perfusion imaging

    SciTech Connect

    Deutsch, E.; Volkert, W.A.

    1991-12-31

    It is well established that small, neutral, lipophilic technetium complexes can diffuse into the brain and then be trapped intracellularly by a variety of mechanisms. A more detailed understanding of the structural and chemical parameters which promote efficient diffusion into the brain, and which underlie the trapping mechanisms, will be necessary to delineate the clinical relevance of current agents, and to design improved technetium 99 pharmaceuticals. Current technetium 99 brain-perfusion imaging agents do not show ideal characteristics of brain uptake and retention. Furthermore, significant fractions of the technetium 99 complexes are lost between site of injection and the brain. Thus, it is difficult to use these current agents to quantitate regional cerebral blood flow. Nevertheless, these agents are proving extremely valuable for the SPECT evaluation of abnormalities in brain perfusion patients with neurological disorders.

  7. Pancreas tumor model in rabbit imaged by perfusion CT scans

    NASA Astrophysics Data System (ADS)

    Gunn, Jason; Tichauer, Kenneth; Moodie, Karen; Kane, Susan; Hoopes, Jack; Stewart, Errol E.; Hadway, Jennifer; Lee, Ting-Yim; Pereira, Stephen P.; Pogue, Brian W.

    2013-03-01

    The goal of this work was to develop and validate a pancreas tumor animal model to investigate the relationship between photodynamic therapy (PDT) effectiveness and photosensitizer drug delivery. More specifically, this work lays the foundation for investigating the utility of dynamic contrast enhanced blood perfusion imaging to be used to inform subsequent PDT. A VX2 carcinoma rabbit cell line was grown in the tail of the pancreas of three New Zealand White rabbits and approximately 3-4 weeks after implantation the rabbits were imaged on a CT scanner using a contrast enhanced perfusion protocol, providing parametric maps of blood flow, blood volume, mean transit time, and vascular permeability surface area product.

  8. 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.

  9. 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

  10. [Imaging of childhood brain tumors].

    PubMed

    Couanet, D; Adamsbaum, C

    2006-06-01

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

  11. 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

  12. Quantitative Perfusion and Permeability Biomarkers in Brain Cancer from Tomographic CT and MR Images

    PubMed Central

    Eilaghi, Armin; Yeung, Timothy; d’Esterre, Christopher; Bauman, Glenn; Yartsev, Slav; Easaw, Jay; Fainardi, Enrico; Lee, Ting-Yim; Frayne, Richard

    2016-01-01

    Dynamic contrast-enhanced perfusion and permeability imaging, using computed tomography and magnetic resonance systems, are important techniques for assessing the vascular supply and hemodynamics of healthy brain parenchyma and tumors. These techniques can measure blood flow, blood volume, and blood–brain barrier permeability surface area product and, thus, may provide information complementary to clinical and pathological assessments. These have been used as biomarkers to enhance the treatment planning process, to optimize treatment decision-making, and to enable monitoring of the treatment noninvasively. In this review, the principles of magnetic resonance and computed tomography dynamic contrast-enhanced perfusion and permeability imaging are described (with an emphasis on their commonalities), and the potential values of these techniques for differentiating high-grade gliomas from other brain lesions, distinguishing true progression from posttreatment effects, and predicting survival after radiotherapy, chemotherapy, and antiangiogenic treatments are presented. PMID:27398030

  13. Parametric imaging of tumor perfusion and neovascular morphology using ultrasound

    NASA Astrophysics Data System (ADS)

    Hoyt, Kenneth

    2015-03-01

    A new image processing strategy is detailed for the simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. A technique for locally mapping tumor perfusion parameters using skeletonized neovascular data is also introduced. Simulated images were used to test the neovascular skeletonization technique and variance (error) of relevant parametric estimates. Preliminary DCE-US image datasets were collected in 6 female patients diagnosed with invasive breast cancer and using a Philips iU22 ultrasound system equipped with a L9-3 MHz transducer and Definity contrast agent. Simulation data demonstrates that neovascular morphology parametric estimation is reproducible albeit measurement error can occur at a lower signal-to-noise ratio (SNR). Experimental results indicate the feasibility of our approach to performing both tumor perfusion and neovascular morphology measurements from DCE-US images. Future work will expand on our initial clinical findings and also extent our image processing strategy to 3-dimensional space to allow whole tumor characterization.

  14. Modelling Brain Temperature and Perfusion for Cerebral Cooling

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2015-11-01

    Brain temperature relies heavily on two aspects: i) blood perfusion and porous heat transport through tissue and ii) blood flow and heat transfer through embedded arterial and venous vasculature. Moreover brain temperature cannot be measured directly unless highly invasive surgical procedures are used. A 3D two-phase fluid-porous model for mapping flow and temperature in brain is presented with arterial and venous vessels extracted from MRI scans. Heat generation through metabolism is also included. The model is robust and reveals flow and temperature maps in unprecedented 3D detail. However, the Karmen-Kozeny parameters of the porous (tissue) phase need to be optimised for expected perfusion profiles. In order to optimise the K-K parameters a reduced order two-phase model is developed where 1D vessels are created with a tree generation algorithm embedded inside a 3D porous domain. Results reveal that blood perfusion is a strong function of the porosity distribution in the tissue. We present a qualitative comparison between the simulated perfusion maps and those obtained clinically. We also present results studying the effect of scalp cooling on core brain temperature and preliminary results agree with those observed clinically.

  15. Pediatric Brain Tumors: An Update.

    PubMed

    Segal, Devorah; Karajannis, Matthias A

    2016-07-01

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

  16. Brain perfusion in acute and chronic hyperglycemia in rats

    SciTech Connect

    Kikano, G.E.; LaManna, J.C.; Harik, S.I. )

    1989-08-01

    Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose.

  17. Synergistic Effects of Hemoglobin and Tumor Perfusion on Tumor Control and Survival in Cervical Cancer

    SciTech Connect

    Mayr, Nina A. Wang, Jian Z.; Zhang Dongqing; Montebello, Joseph F.; Grecula, John C.; Lo, Simon S.; Fowler, Jeffery M.; Yuh, William T.C.

    2009-08-01

    Purpose: The tumor oxygenation status is likely influenced by two major factors: local tumor blood supply (tumor perfusion) and its systemic oxygen carrier, hemoglobin (Hgb). Each has been independently shown to affect the radiotherapy (RT) outcome in cervical cancer. This study assessed the effect of local tumor perfusion, systemic Hgb levels, and their combination on the treatment outcome in cervical cancer. Methods and Materials: A total of 88 patients with cervical cancer, Stage IB2-IVA, who were treated with RT/chemotherapy, underwent serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before RT, at 20-22 Gy, and at 45-50 Gy. The DCE-MRI perfusion parameters, mean and lowest 10th percentile of the signal intensity distribution in the tumor pixels, and the Hgb levels, including pre-RT, nadir, and mean Hgb (average of weekly Hgb during RT), were correlated with local control and disease-specific survival. The median follow-up was 4.6 years. Results: Local recurrence predominated in the group with both a low mean Hgb (<11.2 g/dL) and low perfusion (lowest 10th percentile of signal intensity <2.0 at 20-22 Gy), with a 5-year local control rate of 60% vs. 90% for all other groups (p = .001) and a disease-specific survival rate of 41% vs. 72% (p = .008), respectively. In the group with both high mean Hgb and high perfusion, the 5-year local control rate and disease-specific survival rate was 100% and 78%, respectively. Conclusion: These results suggest that the compounded effects of Hgb level and tumor perfusion during RT influence the radioresponsiveness and survival in cervical cancer patients. The outcome was worst when both were impaired. The management of Hgb may be particularly important in patients with low tumor perfusion.

  18. 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

  19. Clinical Brain Death with False Positive Radionuclide Cerebral Perfusion Scans

    PubMed Central

    Venkatram, Sindhaghatta; Bughio, Sara; Diaz-Fuentes, Gilda

    2015-01-01

    Practice guidelines from the American Academy of Neurology for the determination of brain death in adults define brain death as “the irreversible loss of function of the brain, including the brainstem.” Neurological determination of brain death is primarily based on clinical examination; if clinical criteria are met, a definitive confirmatory test is indicated. The apnea test remains the gold standard for confirmation. In patients with factors that confound the clinical determination or when apnea tests cannot safely be performed, an ancillary test is required to confirm brain death. Confirmatory ancillary tests for brain death include (a) tests of electrical activity (electroencephalography (EEG) and somatosensory evoked potentials) and (b) radiologic examinations of blood flow (contrast angiography, transcranial Doppler ultrasound (TCD), and radionuclide methods). Of these, however, radionuclide studies are used most commonly. Here we present data from two patients with a false positive Radionuclide Cerebral Perfusion Scan (RCPS). PMID:26167307

  20. Dendrimer technologies for brain tumor.

    PubMed

    Mishra, Vijay; Kesharwani, Prashant

    2016-05-01

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

  1. 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 ...

  2. Mismatch between iodine-123 IMP and technetium-99m HM-PAO brain perfusion imaging in a patient with meningioma

    SciTech Connect

    Hoshi, H.; Jinnouchi, S.; Watanabe, K.; Nakano, S.; Kinoshita, K.

    1987-09-01

    The discrepancy between three methods for cerebral perfusion imagings in the case of a man with meningioma is presented. Imaging with N-isopropyl-P-(I-123) iodoamphetamine (IMP) showed no activity in the tumor. Imaging with Tc-99m hexamethylpropyleneamine oxime (HM-PAO) and the local cerebral blood flow (LCBF) image with Xe-133 inhalation showed high tumor activity. IMP is a more accurate method for imaging the brain tissue blood flow.

  3. Rapid decrease in tumor perfusion following VEGF blockade predicts long-term tumor growth inhibition in preclinical tumor models.

    PubMed

    Eichten, Alexandra; Adler, Alexander P; Cooper, Blerta; Griffith, Jennifer; Wei, Yi; Yancopoulos, George D; Lin, Hsin Chieh; Thurston, Gavin

    2013-04-01

    Vascular endothelial growth factor (VEGF) is a key upstream mediator of tumor angiogenesis, and blockade of VEGF can inhibit tumor angiogenesis and decrease tumor growth. However, not all tumors respond well to anti-VEGF therapy. Despite much effort, identification of early response biomarkers that correlate with long-term efficacy of anti-VEGF therapy has been difficult. These difficulties arise in part because the functional effects of VEGF inhibition on tumor vessels are still unclear. We therefore assessed rapid molecular, morphologic and functional vascular responses following treatment with aflibercept (also known as VEGF Trap or ziv-aflibercept in the United States) in preclinical tumor models with a range of responses to anti-VEGF therapy, including Colo205 human colorectal carcinoma (highly sensitive), C6 rat glioblastoma (moderately sensitive), and HT1080 human fibrosarcoma (resistant), and correlated these changes to long-term tumor growth inhibition. We found that an overall decrease in tumor vessel perfusion, assessed by dynamic contrast-enhanced ultrasound (DCE-US), and increases in tumor hypoxia correlated well with long-term tumor growth inhibition, whereas changes in vascular gene expression and microvessel density did not. Our findings support previous clinical studies showing that decreased tumor perfusion after anti-VEGF therapy (measured by DCE-US) correlated with response. Thus, measuring tumor perfusion changes shortly after treatment with VEGF inhibitors, or possibly other anti-angiogenic therapies, may be useful to predict treatment efficacy. PMID:23238831

  4. Technological advances in MRI measurement of brain perfusion.

    PubMed

    Duyn, Jeff H; van Gelderen, Peter; Talagala, Lalith; Koretsky, Alan; de Zwart, Jacco A

    2005-12-01

    Measurement of brain perfusion using arterial spin labeling (ASL) or dynamic susceptibility contrast (DSC) based MRI has many potential important clinical applications. However, the clinical application of perfusion MRI has been limited by a number of factors, including a relatively poor spatial resolution, limited volume coverage, and low signal-to-noise ratio (SNR). It is difficult to improve any of these aspects because both ASL and DSC methods require rapid image acquisition. In this report, recent methodological developments are discussed that alleviate some of these limitations and make perfusion MRI more suitable for clinical application. In particular, the availability of high magnetic field strength systems, increased gradient performance, the use of RF coil arrays and parallel imaging, and increasing pulse sequence efficiency allow for increased image acquisition speed and improved SNR. The use of parallel imaging facilitates the trade-off of SNR for increases in spatial resolution. As a demonstration, we obtained DSC and ASL perfusion images at 3.0 T and 7.0 T with multichannel RF coils and parallel imaging, which allowed us to obtain high-quality images with in-plane voxel sizes of 1.5 x 1.5 mm(2). PMID:16267852

  5. Extra-axial brain tumors.

    PubMed

    Rapalino, Otto; Smirniotopoulos, James G

    2016-01-01

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

  6. 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.

  7. 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.

  8. 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

  9. Optimization of arterial spin labeling MRI for quantitative tumor perfusion in a mouse xenograft model.

    PubMed

    Rajendran, Reshmi; Liang, Jieming; Tang, Mei Yee Annie; Henry, Brian; Chuang, Kai-Hsiang

    2015-08-01

    Perfusion is an important biomarker of tissue function and has been associated with tumor pathophysiology such as angiogenesis and hypoxia. Arterial spin labeling (ASL) MRI allows noninvasive and quantitative imaging of perfusion; however, the application in mouse xenograft tumor models has been challenging due to the low sensitivity and high perfusion heterogeneity. In this study, flow-sensitive alternating inversion recovery (FAIR) ASL was optimized for a mouse xenograft tumor. To assess the sensitivity and reliability for measuring low perfusion, the lumbar muscle was used as a reference region. By optimizing the number of averages and inversion times, muscle perfusion as low as 32.4 ± 4.8 (mean ± standard deviation) ml/100 g/min could be measured in 20 min at 7 T with a quantification error of 14.4 ± 9.1%. Applying the optimized protocol, heterogeneous perfusion ranging from 49.5 to 211.2 ml/100 g/min in a renal carcinoma was observed. To understand the relationship with tumor pathology, global and regional tumor perfusion was compared with histological staining of blood vessels (CD34), hypoxia (CAIX) and apoptosis (TUNEL). No correlation was observed when the global tumor perfusion was compared with these pathological parameters. Regional analysis shows that areas of high perfusion had low microvessel density, which was due to larger vessel area compared with areas of low perfusion. Nonetheless, these were not correlated with hypoxia or apoptosis. The results suggest that tumor perfusion may reflect certain aspect of angiogenesis, but its relationship with other pathologies needs further investigation. PMID:26104980

  10. [Antegrade unilateral perfusion of the brain through the brachiocephalic trunk in operations on the aortic arch].

    PubMed

    Kozlov, B N; Panfilov, D S; Kuznetsov, M S; Ponomarenko, I V; Nasrashvili, G G; Shipulin, V M

    2016-01-01

    Presented herein is a technique of unilateral antegrade perfusion of the brain in operations on the aortic arch. The method makes it possible to perform both systemic artificial circulation and adequate physiological perfusion of the brain, promoting minimization of the number of neurological complications. PMID:27100557

  11. The diagnostic accuracy of multiparametric MRI to determine pediatric brain tumor grades and types.

    PubMed

    Koob, Mériam; Girard, Nadine; Ghattas, Badih; Fellah, Slim; Confort-Gouny, Sylviane; Figarella-Branger, Dominique; Scavarda, Didier

    2016-04-01

    Childhood brain tumors show great histological variability. The goal of this retrospective study was to assess the diagnostic accuracy of multimodal MR imaging (diffusion, perfusion, MR spectroscopy) in the distinction of pediatric brain tumor grades and types. Seventy-six patients (range 1 month to 18 years) with brain tumors underwent multimodal MR imaging. Tumors were categorized by grade (I-IV) and by histological type (A-H). Multivariate statistical analysis was performed to evaluate the diagnostic accuracy of single and combined MR modalities, and of single imaging parameters to distinguish the different groups. The highest diagnostic accuracy for tumor grading was obtained with diffusion-perfusion (73.24 %) and for tumor typing with diffusion-perfusion-MR spectroscopy (55.76 %). The best diagnostic accuracy was obtained for tumor grading in I and IV and for tumor typing in embryonal tumor and pilocytic astrocytoma. Poor accuracy was seen in other grades and types. ADC and rADC were the best parameters for tumor grading and typing followed by choline level with an intermediate echo time, CBV for grading and Tmax for typing. Multiparametric MR imaging can be accurate in determining tumor grades (primarily grades I and IV) and types (mainly pilocytic astrocytomas and embryonal tumors) in children. PMID:26732081

  12. 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

  13. Deregulated proliferation and differentiation in brain tumors.

    PubMed

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

    2015-01-01

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

  14. Primary Neuroendocrine Tumor in Brain

    PubMed Central

    Tamura, Ryota; Kuroshima, Yoshiaki; Nakamura, Yoshiki

    2014-01-01

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

  15. Iterative blind deconvolution in magnetic resonance brain perfusion imaging.

    PubMed

    Grüner, Renate; Taxt, Torfinn

    2006-04-01

    In first pass magnetic resonance brain perfusion imaging, arterial input functions are used in the deconvolution of the observed contrast concentrations to obtain quantitative hemodynamic parameters. Ideally, arterial input functions should be measured in each imaged voxel to eliminate the effects of delay and dispersion of the contrast agent from the injection site. An approach based on iterative blind deconvolution with the Richardson-Lucy algorithm is proposed for the simultaneous estimation of voxel-specific arterial input functions and voxel-specific tissue residue functions. An extended contrast concentration model was used to separate the first pass bolus from additional recirculation and leakage signals. The extended model was evaluated using in vivo data. Computer simulations examined the feasibility of iterative blind deconvolution in perfusion imaging. Preliminary in vivo results from a patient with fibromuscular dysplasia showed territories with delayed/dispersed arterial input functions that coincided with the location of territories supplied by collateral circulation as described from the complete radiologic examination. Higher flow values and shorter mean transit times compared to conventional methods were obtained in these areas, suggesting that the effects of dispersion were minimized. The in vivo estimated arterial input functions visualized the patient's blood supply patterns as a function of time. PMID:16526016

  16. Absolute perfusion measurements and associated iodinated contrast agent time course in brain metastasis: a study for contrast-enhanced radiotherapy

    PubMed Central

    Obeid, Layal; Deman, Pierre; Tessier, Alexandre; Balosso, Jacques; Estève, François; Adam, Jean- François

    2014-01-01

    Contrast-enhanced radiotherapy is an innovative treatment that combines the selective accumulation of heavy elements in tumors with stereotactic irradiations using medium energy X-rays. The radiation dose enhancement depends on the absolute amount of iodine reached in the tumor and its time course. Quantitative, postinfusion iodine biodistribution and associated brain perfusion parameters were studied in human brain metastasis as key parameters for treatment feasibility and quality. Twelve patients received an intravenous bolus of iodinated contrast agent (CA) (40 mL, 4 mL/s), followed by a steady-state infusion (160 mL, 0.5 mL/s) to ensure stable intratumoral amounts of iodine during the treatment. Absolute iodine concentrations and quantitative perfusion maps were derived from 40 multislice dynamic computed tomography (CT) images of the brain. The postinfusion mean intratumoral iodine concentration (over 30 minutes) reached 1.94±0.12 mg/mL. Reasonable correlations were obtained between these concentrations and the permeability surface area product and the cerebral blood volume. To our knowledge, this is the first quantitative study of CA biodistribution versus time in brain metastasis. The study shows that suitable and stable amounts of iodine can be reached for contrast-enhanced radiotherapy. Moreover, the associated perfusion measurements provide useful information for the patient recruitment and management processes. PMID:24447951

  17. Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia.

    PubMed

    Cohen, M B; Lake, R R; Graham, L S; King, M A; Kling, A S; Fitten, L J; O'Rear, J; Bronca, G A; Gan, M; Servrin, R

    1989-10-01

    Decreased perfusion in the frontal lobes of patients with chronic schizophrenia has been reported by multiple observes using a variety of techniques. Other observers have been unable to confirm this finding using similar techniques. In this study quantitative single photon emission computed tomography brain imaging was performed using p,5n [123I]IMP in five normal subjects and ten chronically medicated patients with schizophrenia. The acquisition data were preprocessed with an image dependent Metz filter and reconstructed using a ramp filtered back projection technique. The uptake in each of 50 regions of interest in each subject was normalized to the uptake in the cerebellum. There were no significant confirmed differences in the comparable ratios of normal subjects and patients with schizophrenia even at the p = 0.15 level. "Hypofrontality" was not observed. PMID:2795201

  18. Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia

    SciTech Connect

    Cohen, M.B.; Lake, R.R.; Graham, L.S.; King, M.A.; Kling, A.S.; Fitten, L.J.; O'Rear, J.; Bronca, G.A.; Gan, M.; Servrin, R. )

    1989-10-01

    Decreased perfusion in the frontal lobes of patients with chronic schizophrenia has been reported by multiple observes using a variety of techniques. Other observers have been unable to confirm this finding using similar techniques. In this study quantitative single photon emission computed tomography brain imaging was performed using p,5n ({sup 123}I)IMP in five normal subjects and ten chronically medicated patients with schizophrenia. The acquisition data were preprocessed with an image dependent Metz filter and reconstructed using a ramp filtered back projection technique. The uptake in each of 50 regions of interest in each subject was normalized to the uptake in the cerebellum. There were no significant confirmed differences in the comparable ratios of normal subjects and patients with schizophrenia even at the p = 0.15 level. Hypofrontality was not observed.

  19. Antiangiogenic therapy in brain tumors

    PubMed Central

    Lakka, Sajani S; Rao, Jasti S

    2008-01-01

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

  20. Brain perfusion in polysubstance users: Relationship to substance and tobacco use, cognition, and self-regulation*

    PubMed Central

    Murray, Donna E.; Durazzo, Timothy C.; Mon, Anderson; Schmidt, Thomas P.; Meyerhoff, Dieter J.

    2015-01-01

    Background Brain perfusion is altered in both alcohol dependence and stimulant dependence. Although most substance users also abuse/depend on alcohol concurrently (polysubstance users; PSU), rigorous perfusion research in PSU is limited. Also, the relationships of perfusion abnormalities with cognition, impulsivity or decision making are not well known. Methods Arterial spin labeling MRI and neuropsychological measures assessed perfusion levels and neurocognition in 20 alcohol dependent individuals with comorbid stimulant dependence (PSU), 26 individuals dependent on alcohol only (ALC), and 31 light/non-drinking controls (LD). The patient groups included smokers and non-smokers. Results ALC had lower perfusion than LD in subcortical and cortical brain regions including the brain reward/executive oversight system (BREOS). Contrary to our hypothesis, regional perfusion was generally not lower in PSU than ALC. However, smoking PSU had lower perfusion than smoking ALC in several regions, including BREOS. Lower BREOS perfusion related to greater drinking severity in smoking substance users and to greater smoking severity in smoking ALC. Lower regional perfusion in ALC and PSU correlated with worse performance in different cognitive domains; smoking status affected perfusion-cognition relationships in ALC only. Lower BREOS perfusion in both substance using groups related to higher impulsivity. Conclusion Although regional perfusion was not decreased in PSU as a group, the combination of cigarette smoking and polysubstance use is strongly related to hypoperfusion in important cortical and subcortical regions. As lower perfusion relates to greater smoking severity, worse cognition and higher impulsivity, smoking cessation is warranted for treatment-seeking PSU and ALC. PMID:25772434

  1. Brain Perfusion in Corticobasal Syndrome with Progressive Aphasia

    PubMed Central

    Abe, Yoshitake; Kimura, Noriyuki; Goto, Megumi; Aso, Yasuhiro; Matsubara, Etsuro

    2016-01-01

    Background Brain perfusion may differ between patients with corticobasal syndrome (CBS) with and without aphasia. Methods Twenty-six (9 males and 17 females; mean age 76 ± 5.3 years) patients with CBS were enrolled in the study. Brain MRI and single-photon emission computed tomography were performed in all subjects. Language was evaluated using the Standard Language Test of Aphasia. The patients were divided into two subgroups according to the presence or absence of progressive aphasia. Differences in the regional cerebral blood flow (rCBF) between the two groups were detected based on voxel-by-voxel group analysis using Statistical Parametric Mapping 8. Results All patients exhibited asymmetric motor symptoms and signs, including limb apraxia, bradykinesia, and akinetic rigidity. Of 26 patients, 9 had a clinically obvious language disturbance, characterized as nonfluent aphasia. Almost all CBS patients with aphasia exhibited cortical atrophy predominantly in the left frontal and temporal lobes with widening of the Sylvian fissure on MRI. The rCBF in the left middle frontal gyrus differed significantly between CBS patients with and without aphasia. Conclusion CBS patients with aphasia exhibit motor symptoms predominantly on the right side and cortical atrophy mainly in the left perisylvian cortices. In particular, left frontal dysfunction might be related to nonfluent aphasia in CBS. PMID:27195001

  2. Interobserver variation in diagnosis of dementia by brain perfusion SPECT.

    PubMed

    Honda, Norinari; Machida, Kikuo; Hosono, Makoto; Matsumoto, Tohru; Matsuda, Hiroshi; Oshima, Motoo; Koizumi, Kiyoshi; Kosuda, Shigeru; Momose, Toshimitsu; Mori, Yutaka; Hashimoto, Jun; Shimizu, Yuji

    2002-01-01

    Brain perfusion SPECT (BP-SPECT) has characteristic patterns of abnormality, enabling the differential diagnosis of dementia. The purpose of this study was to measure interobserver variations in the diagnosis of dementia using BP-SPECT. BP-SPECT images of 57 cases, 19 of Alzheimer's disease (AD), eight of multi-infarct dementia (MID), three of Pick's disease, five of other dementias, and 22 normal controls, were interpreted by ten nuclear medicine physicians with varying levels of experience. Brain MR images of the cases were then interpreted apart from SPECT. The physicians independently rated all of the diagnoses listed beforehand according to a five-point scale, with clinical information provided. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (Az) were calculated. Az varied from 0.48 to 0.87. Mean Az's were significantly larger (p<0.05) in the diagnosis by SPECT than in that by MRI (0.715 and 0.629 for dementia vs. normal, 0.670 and 0.560 for AD or MID vs. normal, 0.610 and 0.416 for AD vs. normal, and 0.672 and 0.412 for AD vs. MID, respectively). Considerable interobserver variation was present in BP-SPECT interpretation. BP-SPECT may be more effective for the evaluation of dementia than MRI when the same nuclear medicine physicians interpret both images. PMID:12553341

  3. 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.

  4. Neuropsychological Correlates of Brain Perfusion SPECT in Patients with Macrophagic Myofasciitis

    PubMed Central

    Van Der Gucht, Axel; Aouizerate, Jessie; Evangelista, Eva; Chalaye, Julia; Gherardi, Romain K.; Ragunathan-Thangarajah, Nilusha; Bachoud-Levi, Anne-Catherine; Authier, François-Jérôme

    2015-01-01

    Background Patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis (MMF) complain of arthromyalgias, chronic fatigue and cognitive deficits. This study aimed to characterize brain perfusion in these patients. Methods Brain perfusion SPECT was performed in 76 consecutive patients (aged 49±10 y) followed in the Garches-Necker-Mondor-Hendaye reference center for rare neuromuscular diseases. Images were acquired 30 min after intravenous injection of 925 MBq 99mTc-ethylcysteinate dimer (ECD) at rest. All patients also underwent a comprehensive battery of neuropsychological tests, within 1.3±5.5 mo from SPECT. Statistical parametric maps (SPM12) were obtained for each test using linear regressions between each performance score and brain perfusion, with adjustment for age, sex, socio-cultural level and time delay between brain SPECT and neuropsychological testing. Results SPM analysis revealed positive correlation between neuropsychological scores (mostly exploring executive functions) and brain perfusion in the posterior associative cortex, including cuneus/precuneus/occipital lingual areas, the periventricular white matter/corpus callosum, and the cerebellum, while negative correlation was found with amygdalo-hippocampal/entorhinal complexes. A positive correlation was also observed between brain perfusion and the posterior associative cortex when the time elapsed since last vaccine injection was investigated. Conclusions Brain perfusion SPECT showed a pattern of cortical and subcortical changes in accordance with the MMF-associated cognitive disorder previously described. These results provide a neurobiological substrate for brain dysfunction in aluminum hydroxide adjuvant-induced MMF patients. PMID:26030650

  5. Contrast-enhanced diffuse optical tomography of brain perfusion in humans using ICG

    NASA Astrophysics Data System (ADS)

    Habermehl, Christina; Schmitz, Christoph; Steinbrink, Jens

    2012-02-01

    Regular monitoring of brain perfusion at the bedside in neurointensive care is desirable. Currently used imaging modalities are not suited for constant monitoring and often require a transport of the patient. Noninvasive near infrared spectroscopy (NIRS) in combination with an injection of a safe dye (indocyanine green, ICG) could serve as a quasi-continuous brain perfusion monitor. In this work, we evaluate prerequisites for the development of a brain perfusion monitor using continuous wave (cw) NIRS technique. We present results from a high-resolution diffuse optical tomography (HR-DOT) experiment in humans demonstrating the separation of signals from skin from the brain. This technique can help to monitor neurointensive care patients on a regular basis, detecting changes in cortical perfusion in time.

  6. Intra-procedural Transcatheter Intraarterial Perfusion MRI as a Predictor of Tumor Response to Chemoembolization for Hepatocellular Carcinoma

    PubMed Central

    Wang, Dingxin; Gaba, Ron C.; Jin, Brian; Riaz, Ahsun; Lewandowski, Robert J.; Ryu, Robert K.; Sato, Kent T.; Ragin, Ann B.; Kulik, Laura M.; Mulcahy, Mary F.; Salem, Riad; Larson, Andrew C.; Omary, Reed A.

    2011-01-01

    Rationale and Objectives To prospectively test the hypothesis that transcatheter intraarterial perfusion magnetic resonance imaging (TRIP-MRI) measured semi-quantitative perfusion reductions during transcatheter arterial chemoembolization of hepatocellular carcinoma (HCC) are associated with tumor response. Materials and Methods Twenty eight patients (mean age 63 years; range 47–87 years) with 29 tumors underwent chemoembolization in a combined MR-interventional radiology suite. Intra-procedural tumor perfusion reductions during chemoembolization were monitored using TRIP-MRI. Pre- and post-–chemoembolization semi-quantitative area under the time-signal enhancement curve (AUC) tumor perfusion was measured. Mean tumor perfusion pre- and post-chemoembolization were compared using a paired t-test. Imaging follow-up was performed one to three months after chemoembolization. We studied the relationship between short-term tumor imaging response and intra-procedural perfusion reductions using univariate and multivariate analysis. Results Intra-procedural AUC perfusion value decreased significantly after chemoembolization (342.1 versus 158.6 arbitrary unit, P < 0.001). Twenty six patients with 27 HCCs (n = 27) had follow-up imaging at mean 39 days post-chemoembolization. Favorable response was present in 67% of these treated tumors according to necrosis criteria. 15 of 16 (94%) tumors with 25–75% perfusion reductions showed necrosis treatment response compared to only 3 of 11 (27%) tumors with perfusion reductions outside the above range (P = 0.001). Multivariate logistic regression indicated that intra-procedural tumor perfusion reduction and Child-Pugh class were independent factors associated significantly with tumor response (P = 0.012 and 0.047, respectively). Conclusion TRIP-MRI can successfully measure semi-quantitative changes in HCC perfusion during chemoembolization. Intra-procedural tumor perfusion reductions are associated with future tumor response. PMID

  7. Whole-Brain Computed Tomographic Perfusion Imaging in Acute Cerebral Venous Sinus Thrombosis

    PubMed Central

    Mokin, Maxim; Ciambella, Chelsey C.; Masud, Muhammad W.; Levy, Elad I.; Snyder, Kenneth V.; Siddiqui, Adnan H.

    2016-01-01

    Background Acute cerebral venous sinus thrombosis (VST) can be difficult to diagnose because of its diverse clinical presentation. The utility of perfusion imaging for diagnosing VST is not well understood. Summary We retrospectively reviewed cases of acute VST in patients who underwent whole-brain (320-detector-row) computed tomographic (CT) perfusion imaging in combination with craniocervical CT venography. Perfusion maps that were analyzed included cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time, and time to peak. Among the 10 patients with acute VST included in this study, 9 had perfusion abnormalities. All perfusion abnormalities were localized in areas adjacent to the occluded sinus and did not match typical anterior or posterior circulation arterial territories. Bilateral perfusion deficits were seen in 4 cases. In 2 cases, parenchymal hemorrhage was diagnosed on noncontrast CT imaging; in those cases, focal CBV and CBF were reduced. Key Messages Whole-brain CT perfusion imaging with 320-detector-row scanners can further assist in establishing the diagnosis of VST by detecting perfusion abnormalities corresponding to venous and not arterial territories. CT perfusion could assist in the differentiation between focal reversible changes, such as those caused by vasogenic edema, and irreversible changes due to infarction. PMID:27051406

  8. Radiosensitized treatment of malignant brain tumors

    NASA Astrophysics Data System (ADS)

    Bloznelyte-Plesniene, Laima

    2003-12-01

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

  9. Regional brain perfusion in 10 normal dogs measured using Technetium-99m ethyl cysteinate dimer spect.

    PubMed

    Peremans, K; De Bondt, P; Audenaert, K; Van Laere, K; Gielen, I; Koole, M; Versijpt, J; Van Bree, H; Verschooten, F; Dierckx, R

    2001-01-01

    Single photon emission computed tomography (SPECT) of the brain using perfusion tracers allows estimation of regional brain perfusion. This allows in vivo examination of brain function in the setting of neuropsychologic and pathophysiologic changes. However functional imaging data on brain perfusion in dogs are limited. Hence, the aim of this study was to determine the scintigraphic regional perfusion pattern of the normal canine brain. Ten healthy shepherd type dogs were injected with 925 MBq Technetium-99m ethyl cysteinate (ECD) 20 minutes before the examination. Acquisition was performed using a triple head gamma camera equipped with fanbeam collimators. Uniform attenuation correction and triple energy window correction were applied. Computed tomographic images were obtained from the same dogs, reoriented along the orbito-meatal axis and SPECT perfusion data were coregistered to the CT-volume data. Based on morphological and suggested brain divisions, regions-of-interest (ROIs) were defined for the bilateral frontocerebral, temporocerebral, parietocerebral, occipitocerebral, cerebellar, thalamic, and striatal area. Regional count density was normalized on total counts. All dogs had the highest uptake in the thalamic/striatal area compared to a rather homogeneous cerebral uptake. No significant left/right count differences were found, but a rostro-caudal gradient (+12-13%) was present. In this group, age and gender did not influence the perfusion pattern. PMID:11768526

  10. Pattern of brain blood perfusion in tinnitus patients using technetium-99m SPECT imaging

    PubMed Central

    Mahmoudian, Saeid; Farhadi, Mohammad; Gholami, Saeid; Saddadi, Fariba; Karimian, Ali Reza; Mirzaei, Mohammad; Ghoreyshi, Esmaeel; Ahmadizadeh, Majid; Lenarz, Thomas

    2012-01-01

    Background and Purpose: Tinnitus is associated with an increased activity in central auditory system as demonstrated by neuroimaging studies. Brain perfusion scanning using single photon emission computed tomography (SPECT) was done to understand the pattern of brain blood perfusion of tinnitus subjects and find the areas which are mostly abnormal in these patients. Materials and Methods: A number of 122 patients with tinnitus were enrolled to this cross-sectional study. They underwent SPECT and magnetic resonance imaging (MRI) of brain, and the images were fused to find the regions with abnormal perfusion. Results: SPECT scan results were abnormal in 101 patients (83%). Most patients had bilateral abnormal perfusion (N = 65, 53.3%), and most subjects had abnormality in middle-temporal gyrus (N = 83, 68%) and temporoparietal cortex (N = 46, 37.7%). Patients with multifocal involvement had the least mean age than other 2 groups (patients with no abnormality and unifocal abnormality) (P value = 0.045). Conclusions: Brain blood perfusion pattern differs in patient with tinnitus than others. These patients have brain perfusion abnormality, mostly in auditory gyrus (middle temporal) and associative cortex (temporoparietal cortex). Multifocal abnormalities might be due to more cognitive and emotional brain centers involvement due to tinnitus or more stress and anxiety of tinnitus in the young patients. PMID:23267375

  11. 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 ...

  12. Correction for partial volume effects in brain perfusion ECT imaging

    NASA Astrophysics Data System (ADS)

    Koole, Michel; Staelens, Steven; Van de Walle, Rik; Lemahieu, Ignace L.

    2003-05-01

    The accurate quantification of brain perfusion for emission computed tomography data (PET-SPECT) is limited by partial volume effects (PVE). This study presents a new approach to estimate accurately the true tissue tracer activity within the grey matter tissue compartment. The methodology is based on the availability of additional anatomical side information and on the assumption that activity concentration within the white matter tissue compartment is constant. Starting from an initial estimate for the white matter grey matter activity, the true tracer activity within the grey matter tissue compartment is estimated by an alternating ML-EM-algorithm. During the updating step the constant activity concentration within the white matter compartment is modelled in the forward projection in order to reconstruct the true activity distribution within the grey matter tissue compartment, hence reducing partial volume averaging. Consequently the estimate for the constant activity in the white matter tissue compartment is updated based on the new estimated activity distribution in the grey matter tissue compartment. We have tested this methodology by means of computer simulations. A T1-weighted MR brainscan of a patient was segmented into white matter, grey matter and cerebrospinal fluid, using the segmentation package of the SPM-software (Statistical Parametric Mapping). The segmented grey and white matter were used to simulate a SPECT acquisition, modelling the noise and the distance dependant detector response. Scatter and attenuation were ignored. Following the above described strategy, simulations have shown it is possible to reconstruct the true activity distribution for the grey matter tissue compartment (activity/tissue volume), assuming constant activity in the white matter tissue compartment.

  13. Optimization of perfusion CT protocol for imaging of extracranial head and neck tumors.

    PubMed

    Bisdas, Sotirios; Foo, Chuan Zhi; Thng, Choon Hua; Vogl, Thomas J; Koh, Tong San

    2009-10-01

    The in vivo assessment of physiological processes associated with microcirculation in the head and neck tissue by means of perfusion computed tomography is widely used in the management of patients with head and neck tumors. However, there is no systematic consideration of the total acquisition duration and placement of the scans. A simulation study for optimizing perfusion studies of extracranial head and neck tumors, with considerations of reducing radiation dose while maintaining accuracy of the perfusion parameters, is demonstrated here. The suggested that dual-phase optimized protocols may provide reliable estimations of the permeability surface area product as well as blood flow and volume without additional radiation burden and serious patient discomfort. These optimized protocols can potentially be useful in the clinical setting of examining patients with extracranial head and neck tumors. PMID:18454289

  14. Low contrast medium and radiation dose for hepatic computed tomography perfusion of rabbit VX2 tumor

    PubMed Central

    Zhang, Cai-Yuan; Cui, Yan-Fen; Guo, Chen; Cai, Jing; Weng, Ya-Fang; Wang, Li-Jun; Wang, Deng-Bin

    2015-01-01

    AIM: To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography (CT) perfusion of rabbit VX2 tumor. METHODS: Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential (120 kVp) protocol with 350 mgI/mL contrast medium and filtered back projection, and a low tube potential (80 kVp) protocol with 270 mgI/mL contrast medium with iterative reconstruction. Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor. Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated. RESULTS: A 38% reduction in contrast medium dose (360.1 ± 13.3 mgI/kg vs 583.5 ± 21.5 mgI/kg, P < 0.001) and a 73% decrease in radiation dose (1898.5 mGy • cm vs 6951.8 mGy • cm) were observed. Interestingly, there was a strong positive correlation in hepatic arterial perfusion (r = 0.907, P < 0.001; r = 0.879, P < 0.001), hepatic portal perfusion (r = 0.819, P = 0.002; r = 0.831, P = 0.002), and hepatic blood flow (r = 0.945, P < 0.001; r = 0.930, P < 0.001) as well as a moderate correlation in hepatic perfusion index (r = 0.736, P = 0.01; r = 0.636, P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor. These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumor-to-liver CNR during arterial and portal venous phases (5.63 ± 2.38 vs 6.16 ± 2.60, P = 0.814; 4.60 ± 1.27 vs 5.11 ± 1.74, P = 0.587). CONCLUSION: Compared with the conventional protocol, low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor. PMID:25954099

  15. 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

  16. 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

  17. Malignant metastatic carcinoid presenting as brain tumor.

    PubMed

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

    2016-01-01

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

  18. Intraoperative infrared imaging of brain tumors

    PubMed Central

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

    2014-01-01

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

  19. Brain Tumor Epidemiology Consortium Membership Information

    Cancer.gov

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

  20. Brain Tumors - Multiple Languages: MedlinePlus

    MedlinePlus

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

  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. 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

  3. 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

  4. Repeated Positron Emission Tomography-Computed Tomography and Perfusion-Computed Tomography Imaging in Rectal Cancer: Fluorodeoxyglucose Uptake Corresponds With Tumor Perfusion

    SciTech Connect

    Janssen, Marco H.M.; Aerts, Hugo J.W.L.; Buijsen, Jeroen; Lambin, Philippe; Lammering, Guido; Oellers, Michel C.

    2012-02-01

    Purpose: The purpose of this study was to analyze both the intratumoral fluorodeoxyglucose (FDG) uptake and perfusion within rectal tumors before and after hypofractionated radiotherapy. Methods and Materials: Rectal cancer patients, referred for preoperative hypofractionated radiotherapy (RT), underwent FDG-positron emission tomography (PET)-computed tomography (CT) and perfusion-CT (pCT) imaging before the start of hypofractionated RT and at the day of the last RT fraction. The pCT-images were analyzed using the extended Kety model, quantifying tumor perfusion with the pharmacokinetic parameters K{sup trans}, v{sub e}, and v{sub p}. The mean and maximum FDG uptake based on the standardized uptake value (SUV) and transfer constant (K{sup trans}) within the tumor were correlated. Also, the tumor was subdivided into eight subregions and for each subregion the mean and maximum SUVs and K{sup trans} values were assessed and correlated. Furthermore, the mean FDG uptake in voxels presenting with the lowest 25% of perfusion was compared with the FDG uptake in the voxels with the 25% highest perfusion. Results: The mean and maximum K{sup trans} values were positively correlated with the corresponding SUVs ({rho} = 0.596, p = 0.001 and {rho} = 0.779, p < 0.001). Also, positive correlations were found for K{sup trans} values and SUVs within the subregions (mean, {rho} = 0.413, p < 0.001; and max, {rho} = 0.540, p < 0.001). The mean FDG uptake in the 25% highest-perfused tumor regions was significantly higher compared with the 25% lowest-perfused regions (10.6% {+-} 5.1%, p = 0.017). During hypofractionated radiotherapy, stable mean (p = 0.379) and maximum (p = 0.280) FDG uptake levels were found, whereas the mean (p = 0.040) and maximum (p = 0.003) K{sup trans} values were found to significantly increase. Conclusion: Highly perfused rectal tumors presented with higher FDG-uptake levels compared with relatively low perfused tumors. Also, intratumor regions with a high FDG

  5. Embryonal brain tumors and developmental control genes

    SciTech Connect

    Aguzzi, A.

    1995-12-31

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

  6. Atrasentan (ABT-627) enhances perfusion and reduces hypoxia in a human tumor xenograft model

    PubMed Central

    Yang, Kwang Mo; Russell, James; Lupu, Mihaela E.; Cho, HyungJoon; Li, Xiao-Feng; Koutcher, Jason A.; Ling, C. Clifton

    2010-01-01

    The endothelin-1 antagonist, Atrasentan (ABT-627) was used to modify perfusion in the human tumor xenograft model, HT29, growing in nude mice. Atrasentan produced a significant increase in perfusion, as measured in vivo by Gd-DTPA DCE-MRI. Changes in tumor hypoxia were assessed by comparing the binding of two hypoxia tracers, pimonidazole and EF5 given before and after Atrasentan administration. In vehicle-treated controls, the distribution of EF5 and pimonidazole was very similar. However, Atrasentan treatment was associated with decreased uptake of the second hypoxia tracer (EF5), relative to the first (pimonidazole). Although Atrasentan had no independent effect on the growth of HT29 tumors, Atrasentan combined with 20 Gy radiation led to a modest but significant increase in tumor growth delay compared to radiation alone. PMID:19717985

  7. Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis

    PubMed Central

    Bennink, Edwin; Oosterbroek, Jaap; Horsch, Alexander D.; Dankbaar, Jan Willem; Velthuis, Birgitta K.; Viergever, Max A.; de Jong, Hugo W. A. M.

    2015-01-01

    Objectives Although CT scanners generally allow dynamic acquisition of thin slices (1 mm), thick slice (≥5 mm) reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP) reconstruction may suffer less from partial volume effects, and thus yield more accurate quantitative results with increased resolution. Before thin slice protocols are to be introduced clinically, it needs to be ensured that this does not affect overall CTP constancy. We studied the influence of thin slice reconstruction on average perfusion values by comparing it with standard thick slice reconstruction. Materials and Methods From 50 patient studies, absolute and relative hemisphere averaged estimates of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability-surface area product (PS) were analyzed using 0.8, 2.4, 4.8, and 9.6 mm slice reconstructions. Specifically, the influence of Gaussian and bilateral filtering, the arterial input function (AIF), and motion correction on the perfusion values was investigated. Results Bilateral filtering gave noise levels comparable to isotropic Gaussian filtering, with less partial volume effects. Absolute CBF, CBV and PS were 22%, 14% and 46% lower with 0.8 mm than with 4.8 mm slices. If the AIF and motion correction were based on thin slices prior to reconstruction of thicker slices, these differences reduced to 3%, 4% and 3%. The effect of slice thickness on relative values was very small. Conclusions This study shows that thin slice reconstruction for CTP with unaltered acquisition protocol gives relative perfusion values without clinically relevant bias. It does however affect absolute perfusion values, of which CBF and CBV are most sensitive. Partial volume effects in large arteries and veins lead to overestimation of these values. The effects of reconstruction slice thickness should be taken into account when absolute perfusion values are

  8. 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) ...

  9. 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

  10. The proteomics of pediatric brain tumors.

    PubMed

    Anagnostopoulos, Athanasios K; Tsangaris, George T

    2014-10-01

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

  11. Challenges for non-invasive brain perfusion quantification using arterial spin labeling.

    PubMed

    Sousa, I; Santos, N; Sanches, J; Figueiredo, P

    2011-03-29

    Arterial Spin Labeling (ASL) sequences for perfusion Magnetic Resonance Imaging (MRI) have recently become available to be used in the clinical practice, offering a completely non-invasive technique for the quantitative evaluation of brain perfusion. Despite its great potential, ASL perfusion imaging still presents important methodological challenges before its incorporation in routine protocols. Specifically, in some pathological conditions in which the cerebrovascular dynamics is altered, the standard application of ASL may lead to measurement errors. In these cases, it would be possible to estimate perfusion, as well as arterial transit times, by collecting images at multiple time points and then fitting a mathematical model to the data. This approach can be optimized by selecting a set of optimal imaging time points and incorporating knowledge about the physiological distributions of the parameters into the model estimation procedures. In this study, we address the challenges that arise in the measurement of brain perfusion using PASL, due to variations in the arterial transit times, by estimating the errors produced using different types of acquisitions and proposing methods for minimizing such errors. We show by simulation that multiple inversion time ASL acquisitions are expected to reduce measurement errors relative to standard approaches. In data collected from a group of subjects, we further observed reduced inter-subject variability in perfusion measurements when using a multiple versus single inversion time acquisitions. Both measurement errors and variability were further reduced if optimized acquisition and analysis techniques were employed. PMID:24059574

  12. Validation techniques for quantitative brain tumors measurements.

    PubMed

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

    2005-01-01

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

  13. Recent developments in brain tumor predisposing syndromes.

    PubMed

    Johansson, Gunnar; Andersson, Ulrika; Melin, Beatrice

    2016-01-01

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

  14. MRI and MRS of human brain tumors.

    PubMed

    Hou, Bob L; Hu, Jiani

    2009-01-01

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

  15. 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.

  16. Cerebral abnormalities in cocaine abusers: Demonstration by SPECT perfusion brain scintigraphy. Work in progress

    SciTech Connect

    Tumeh, S.S.; Nagel, J.S.; English, R.J.; Moore, M.; Holman, B.L. )

    1990-09-01

    Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT.

  17. 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

  18. 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

  19. 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

  20. [MR spectroscopy in brain tumors].

    PubMed

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

    2007-06-01

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

  1. Confronting pediatric brain tumors: parent stories.

    PubMed

    McMillan, Gigi

    2014-01-01

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

  2. Correlation of oxygenation and perfusion sensitive MRI with invasive micro probe measurements in healthy mice brain.

    PubMed

    Sedlacik, Jan; Reitz, Matthias; Bolar, Divya S; Adalsteinsson, Elfar; Schmidt, Nils O; Fiehler, Jens

    2015-03-01

    The non-invasive assessment of (patho-)physiological parameters such as, perfusion and oxygenation, is of great importance for the characterization of pathologies e.g., tumors, which may be helpful to better predict treatment response and potential outcome. To better understand the influence of physiological parameters on the investigated oxygenation and perfusion sensitive MRI methods, MRI measurements were correlated with subsequent invasive micro probe measurements during free breathing conditions of air, air+10% CO2 and 100% O2 in healthy mice brain. MRI parameters were the irreversible (R2), reversible (R2') and effective (R2*) transverse relaxation rates, venous blood oxygenation level assessed by quantitative blood oxygenation level dependent (qBOLD) method and cerebral blood flow (CBF) assessed by arterial spin labeling (ASL) using a 7 T small animal MRI scanner. One to two days after MRI, tissue perfusion and pO2 were measured by Laser-Doppler flowmetry and fluorescence quenching micro probes, respectively. The tissue pO2 values were converted to blood oxygen saturation by using the Hill equation. The animals were anesthetized by intra peritoneal injection of ketamine-xylazine-acepromazine (10-2-0.3 mg/ml · kg). Results for normal/hypercapnia/hyperoxia conditions were: R2[s(∧)-1] = 20.7/20.4/20.1, R2*[s(∧)-1] = 31.6/29.6/25.9, R2'[s-(∧)1] = 10.9/9.2/5.7, qBOLD venous blood oxygenation level = 0.43/0.51/0.56, CBF[ml · min(∧)-1 · 100 g(∧)-1] = 70.6/105.5/81.8, Laser-Doppler flowmetry[a.u.] = 89.2/120.2/90.6 and pO2[mmHg] = 6.3/32.3/46.7. All parameters were statistically significantly different with P < 0.001 between all breathing conditions. All MRI and the corresponding micro probe measurements were also statistically significantly (P ≤ 0.03) correlated with each other. However, converting the tissue pO2 to blood oxygen saturation = 0.02/0.34/0.63, showed only very limited agreement with the qBOLD venous blood oxygenation level. We found

  3. Perfused drop microfluidic device for brain slice culture-based drug discovery.

    PubMed

    Liu, Jing; Pan, Liping; Cheng, Xuanhong; Berdichevsky, Yevgeny

    2016-06-01

    Living slices of brain tissue are widely used to model brain processes in vitro. In addition to basic neurophysiology studies, brain slices are also extensively used for pharmacology, toxicology, and drug discovery research. In these experiments, high parallelism and throughput are critical. Capability to conduct long-term electrical recording experiments may also be necessary to address disease processes that require protein synthesis and neural circuit rewiring. We developed a novel perfused drop microfluidic device for use with long term cultures of brain slices (organotypic cultures). Slices of hippocampus were placed into wells cut in polydimethylsiloxane (PDMS) film. Fluid level in the wells was hydrostatically controlled such that a drop was formed around each slice. The drops were continuously perfused with culture medium through microchannels. We found that viable organotypic hippocampal slice cultures could be maintained for at least 9 days in vitro. PDMS microfluidic network could be readily integrated with substrate-printed microelectrodes for parallel electrical recordings of multiple perfused organotypic cultures on a single MEA chip. We expect that this highly scalable perfused drop microfluidic device will facilitate high-throughput drug discovery and toxicology. PMID:27194028

  4. Monitoring therapeutic monoclonal antibodies in brain tumor

    PubMed Central

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

    2014-01-01

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

  5. Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core.

    PubMed

    Lin, Longting; Bivard, Andrew; Krishnamurthy, Venkatesh; Levi, Christopher R; Parsons, Mark W

    2016-06-01

    Purpose To validate the use of perfusion computed tomography (CT) with whole-brain coverage to measure the ischemic penumbra and core and to compare its performance to that of limited-coverage perfusion CT. Materials and Methods Institutional ethics committee approval and informed consent were obtained. Patients (n = 296) who underwent 320-detector CT perfusion within 6 hours of the onset of ischemic stroke were studied. First, the ischemic volume at CT perfusion was compared with the penumbra and core reference values at magnetic resonance (MR) imaging to derive CT perfusion penumbra and core thresholds. Second, the thresholds were tested in a different group of patients to predict the final infarction at diffusion-weighted imaging 24 hours after CT perfusion. Third, the change in ischemic volume delineated by the optimal penumbra and core threshold was determined as the brain coverage was gradually reduced from 160 mm to 20 mm. The Wilcoxon signed-rank test, concordance correlation coefficient (CCC), and analysis of variance were used for the first, second, and third steps, respectively. Results CT perfusion at penumbra and core thresholds resulted in the least volumetric difference from MR imaging reference values with delay times greater than 3 seconds and delay-corrected cerebral blood flow of less than 30% (P = .34 and .33, respectively). When the thresholds were applied to the new group of patients, prediction of the final infarction was allowed with delay times greater than 3 seconds in patients with no recanalization of the occluded artery (CCC, 0.96 [95% confidence interval: 0.92, 0.98]) and with delay-corrected cerebral blood flow less than 30% in patients with complete recanalization (CCC, 0.91 [95% confidence interval: 0.83, 0.95]). However, the ischemic volume with a delay time greater than 3 seconds was underestimated when the brain coverage was reduced to 80 mm (P = .04) and the core volume measured as cerebral blood flow less than 30% was

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

    PubMed

    Weller, M

    2008-02-01

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

  7. The cerebral imaging using vessel-around method in the perfusion CT of the human brain

    NASA Astrophysics Data System (ADS)

    Ahn, Choong-Il; Choi, Seung-Wook; Park, Seung-Chul; Shin, Yeong-Gil; Kim, Jae-Hyoung; Chong, Gi-Bong

    2005-04-01

    Perfusion CT has been successfully used as a functional imaging technique for diagnosis of patients with hyperacute stroke. However, the commonly used methods based on curve-fitting are time consuming. Numerous researchers have investigated to what extent Perfusion CT can be used for the quantitative assessment of cerebral ischemia and to rapidly obtain comprehensive information regarding the extent of ischemic damage in acute stroke patients. The aim of this study is to propose an alternative approach to rapidly obtain the brain perfusion mapping and to show the proposed cerebral flow imaging of the vessel and tissue in human brain be reliable and useful. Our main design concern was algorithmic speed, robustness and automation in order to allow its potential use in the emergency situation of acute stroke. To obtain a more effective mapping, we analyzed the signal characteristics of Perfusion CT and defined the vessel-around model which includes the vessel and tissue. We proposed a nonparametric vessel-around approach which automatically discriminates the vessel and tissue around vessel from non-interested brain matter stratifying the level of maximum enhancement of pixel-based TAC. The stratification of pixel-based TAC was executed using the mean and standard deviation of the signal intensity of each pixel and mapped to the cerebral flow imaging. The defined vessel-around model was used to show the cerebral flow imaging and to specify the area of markedly reduced perfusion with loss of function of still viable neurons. Perfusion CT is a fast and practical technique for routine clinical application. It provides substantial and important additional information for the selection of the optimal treatment strategy for patients with hyperacute stroke. The vessel-around approach reduces the computation time significantly when compared with the perfusion imaging using the GVF. The proposed cerebral imaging shows reliable results which are validated by physicians and

  8. 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

  9. Brain tumors: Special characters for research and banking

    PubMed Central

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

    2015-01-01

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

  10. Ion transporters in brain tumors

    PubMed Central

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

    2015-01-01

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

  11. The kynurenine pathway in brain tumor pathogenesis.

    PubMed

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

    2012-11-15

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

  12. Dependence of Brain Intravoxel Incoherent Motion Perfusion Parameters on the Cardiac Cycle

    PubMed Central

    Federau, Christian; Hagmann, Patric; Maeder, Philippe; Müller, Markus; Meuli, Reto; Stuber, Matthias; O’Brien, Kieran

    2013-01-01

    Measurement of microvascular perfusion with Intravoxel Incoherent Motion (IVIM) MRI is gaining interest. Yet, the physiological influences on the IVIM perfusion parameters (“pseudo-diffusion” coefficient D*, perfusion fraction f, and flow related parameter fD*) remain insufficiently characterized. In this article, we hypothesize that D* and fD*, which depend on blood speed, should vary during the cardiac cycle. We extended the IVIM model to include time dependence of D* = D*(t), and demonstrate in the healthy human brain that both parameters D* and fD* are significantly larger during systole than diastole, while the diffusion coefficient D and f do not vary significantly. The results non-invasively demonstrate the pulsatility of the brain’s microvasculature. PMID:24023649

  13. Effects of perfusion on the mechanical behavior of the brain-exposed to hypergravity.

    PubMed

    Guillaume, A; Osmont, D; Gaffie, D; Sarron, J C; Quandieu, P

    1997-04-01

    In certain flight configurations, fighter pilots are exposed to high Gz acceleration which may induce inflight loss of consciousness (G-LOC). In order to study the mechanical effects induced by these accelerations on the cerebral structures, an experimental model has been developed in vitro. Fresh bovine brains were excised and placed in a transparent mold modeling the inside of the skull. Half of these brains were perfused during the experiment. This assembly was placed into the gondola of a centrifuge, in front of a camera lens. Displacements and deformations of the brains were filmed and recorded at different onset rates. Measurements were made after off-line digitalization of images. Experimental data were incorporated into a finite element calculation code whose mesh represented the brain. The applied behavior law was elastic, the structure being considered as homogeneous and isotropic. The first results concerned the elastic properties of the brains under hypergravity. The mean value of the Young's modulus of the nonperfused brain was 46.8 kPa, which corresponded to the values published in reference literature. For the perfused brains, the mean value of the Young's modulus was higher. The mean value of the equivalent Poisson's ratio was 0.35. In fact, contrary to impacts, the mechanical stimulation is long enough to allow fluid displacements. The mean value of the equivalent Poisson's ratio calculated in the present study should probably be increased since this study was performed post mortem. PMID:9075007

  14. Voxel-by-voxel analysis of brain SPECT perfusion in Fibromyalgia

    NASA Astrophysics Data System (ADS)

    Guedj, Eric; Taïeb, David; Cammilleri, Serge; Lussato, David; de Laforte, Catherine; Niboyet, Jean; Mundler, Olivier

    2007-02-01

    We evaluated brain perfusion SPECT at rest, without noxious stiumuli, in a homogeneous group of hyperalgesic FM patients. We performed a voxel-based analysis in comparison to a control group, matched for age and gender. Under such conditions, we made the assumption that significant cerebral perfusion abnormalities could be demonstrated, evidencing altered cerebral processing associated with spontaneous pain in FM patients. The secondary objective was to study the reversibility and the prognostic value of such possible perfusion abnormalities under specific treatment. Eighteen hyperalgesic FM women (mean age 48 yr; range 25-63 yr; ACR criteria) and 10 healthy women matched for age were enrolled in the study. A voxel-by-voxel group analysis was performed using SPM2 ( p<0.05, corrected for multiple comparisons). All brain SPECT were performed before any change was made in therapy in the pain care unit. A second SPECT was performed a month later after specific treatment by Ketamine. Compared to control subjects, we observed individual brain SPECT abnormalities in FM patients, confirmed by SPM2 analysis with hyperperfusion of the somatosensory cortex and hypoperfusion of the frontal, cingulate, medial temporal and cerebellar cortices. We also found that a medial frontal and anterior cingulate hypoperfusions were highly predictive (PPV=83%; NPV=91%) of non-response on Ketamine, and that only responders showed significant modification of brain perfusion, after treatment. In the present study performed without noxious stimuli in hyperalgesic FM patients, we found significant hyperperfusion in regions of the brain known to be involved in sensory dimension of pain processing and significant hypoperfusion in areas assumed to be associated with the affective dimension. As current pharmacological and non-pharmacological therapies act differently on both components of pain, we hypothesize that SPECT could be a valuable and readily available tool to guide individual therapeutic

  15. Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors.

    PubMed

    Stapleton, Shawn; Mirmilshteyn, Daniel; Zheng, Jinzi; Allen, Christine; Jaffray, David A

    2016-01-01

    The heterogeneous intra-tumoral accumulation of liposomes is a critical determinant of their efficacy. Both the chaotic tumor microcirculation and elevated IFP are linked to the heterogeneous intra-tumoral distribution of nanotechnology-based drug delivery systems such as liposomes. In the present study, the relationship between tumor microcirculation, elevated IFP, and accumulation of nanoparticles was investigated through in vivo experimentation. This was accomplished by evaluation of the tumor microcirculation using dynamic contrast enhanced computed tomography (DCE-CT) and measurement of tumor IFP using a novel image-guided robotic needle placement system connected to the micro-CT scanner. The intra-tumoral accumulation of liposomes was determined by CT image-based assessment of a nanoparticle liposomal formulation that stably encapsulate the contrast agent iohexol (CT-liposomes). CT imaging allowed for co-localization of the spatial distribution of tumor hemodynamics, IFP and CT-liposome accumulation in an individual subcutaneous xenograft mouse model of breast cancer. Measurements led to the discovery that perfusion and plasma volume fraction are strong mediators of the intra-tumoral distribution of liposomes. Furthermore, the results suggest that IFP plays an indirect role in mediating liposome distribution through modulating blood flow. PMID:27583578

  16. Three-dimensional analysis for radio-frequency ablation of liver tumor with blood perfusion effect.

    PubMed

    Sheu, Tony W H; Chou, C W; Tsai, S F; Liang, P C

    2005-08-01

    Increase of temperature above 50 approximately 60 degrees C for few minutes by the emitted radio-frequency (RF) energy has been shown to be able to denaturate the intracellular proteins and destruct membranes of tumor cells. To improve the efficacy of this thermal therapy, it is important to investigate factors that may affect the RF heating characteristics for the hepatocellular carcinoma and metastatic liver tumors. In order to make sure the applied RF energy is adequate to ablate the target tumor, a 3D thermoelectric analysis for the system consisting of liver, liver arteries and 4 mm diameter tumor is conducted. The effect of blood perfusion is addressed in this study. PMID:16298845

  17. Acute effect of a high nitrate diet on brain perfusion in older adults

    PubMed Central

    Presley, Tennille D.; Morgan, Ashley R.; Bechtold, Erika; Clodfelter, William; Dove, Robin W.; Jennings, Janine M.; Kraft, Robert A.; King, S. Bruce; Laurienti, Paul J.; Rejeski, W. Jack; Burdette, Jonathan H.; Kim-Shapiro, Daniel B.; Miller, Gary D.

    2010-01-01

    Aims Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. Methods and Results In this investigation we administered a high vs. low nitrate diet to older adults (74.7 ± 6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. Conclusion These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning. PMID:20951824

  18. Targeting tumor perfusion and oxygenation to improve the outcome of anticancer therapy.

    PubMed

    Jordan, Bénédicte F; Sonveaux, Pierre

    2012-01-01

    Radiotherapy and chemotherapy are widespread clinical modalities for cancer treatment. Among other biological influences, hypoxia is a main factor limiting the efficacy of radiotherapy, primarily because oxygen is involved in the stabilization of the DNA damage caused by ionizing radiations. Radiobiological hypoxia is found in regions of rodent and human tumors with a tissue oxygenation level below 10 mmHg at which tumor cells become increasingly resistant to radiation damage. Since hypoxic tumor cells remain clonogenic, their resistance to the treatment strongly influences the therapeutic outcome of radiotherapy. There is therefore an urgent need to identify adjuvant treatment modalities aimed to increase tumor pO(2) at the time of radiotherapy. Since tumor hypoxia fundamentally results from an imbalance between oxygen delivery by poorly efficient blood vessels and oxygen consumption by tumor cells with high metabolic activities, two promising approaches are those targeting vascular reactivity and tumor cell respiration. This review summarizes the current knowledge about the development and use of tumor-selective vasodilators, inhibitors of tumor cell respiration, and drugs and treatments combining both activities in the context of tumor sensitization to X-ray radiotherapy. Tumor-selective vasodilation may also be used to improve the delivery of circulating anticancer agents to tumors. Imaging tumor perfusion and oxygenation is of importance not only for the development and validation of such combination treatments, but also to determine which patients could benefit from the therapy. Numerous techniques have been developed in the preclinical setting. Hence, this review also briefly describes both magnetic resonance and non-magnetic resonance in vivo methods and compares them in terms of sensitivity, quantitative or semi-quantitative properties, temporal, and spatial resolutions, as well as translational aspects. PMID:22661950

  19. Targeting Tumor Perfusion and Oxygenation to Improve the Outcome of Anticancer Therapy1

    PubMed Central

    Jordan, Bénédicte F.; Sonveaux, Pierre

    2012-01-01

    Radiotherapy and chemotherapy are widespread clinical modalities for cancer treatment. Among other biological influences, hypoxia is a main factor limiting the efficacy of radiotherapy, primarily because oxygen is involved in the stabilization of the DNA damage caused by ionizing radiations. Radiobiological hypoxia is found in regions of rodent and human tumors with a tissue oxygenation level below 10 mmHg at which tumor cells become increasingly resistant to radiation damage. Since hypoxic tumor cells remain clonogenic, their resistance to the treatment strongly influences the therapeutic outcome of radiotherapy. There is therefore an urgent need to identify adjuvant treatment modalities aimed to increase tumor pO2 at the time of radiotherapy. Since tumor hypoxia fundamentally results from an imbalance between oxygen delivery by poorly efficient blood vessels and oxygen consumption by tumor cells with high metabolic activities, two promising approaches are those targeting vascular reactivity and tumor cell respiration. This review summarizes the current knowledge about the development and use of tumor-selective vasodilators, inhibitors of tumor cell respiration, and drugs and treatments combining both activities in the context of tumor sensitization to X-ray radiotherapy. Tumor-selective vasodilation may also be used to improve the delivery of circulating anticancer agents to tumors. Imaging tumor perfusion and oxygenation is of importance not only for the development and validation of such combination treatments, but also to determine which patients could benefit from the therapy. Numerous techniques have been developed in the preclinical setting. Hence, this review also briefly describes both magnetic resonance and non-magnetic resonance in vivo methods and compares them in terms of sensitivity, quantitative or semi-quantitative properties, temporal, and spatial resolutions, as well as translational aspects. PMID:22661950

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

    PubMed

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

    2015-08-01

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

  1. Home care for brain tumor patients

    PubMed Central

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

    2014-01-01

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

  2. Cholinergic and perfusion brain networks in Parkinson disease dementia

    PubMed Central

    McKeith, Ian G.; Burn, David J.; Wyper, David J.; O'Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. Methods: Forty-nine participants (25 PDD and 24 elderly controls) underwent 123I-QNB and 99mTc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). Results: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor–naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. Conclusion: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition. PMID:27306636

  3. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

    PubMed Central

    Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

  4. Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury: acute versus chronic disturbances?

    PubMed

    Metting, Zwany; Spikman, Jacoba M; Rödiger, Lars A; van der Naalt, Joukje

    2014-04-01

    In a subgroup of patients with mild traumatic brain injury (TBI) residual symptoms, interfering with outcome and return to work, are found. With neuropsychological assessment cognitive deficits can be demonstrated although the pathological underpinnings of these cognitive deficits are not fully understood. As the admission computed tomography (CT) often is normal, perfusion CT imaging may be a useful indicator of brain dysfunction in the acute phase after injury in these patients. In the present study, directly after admission perfusion CT imaging was performed in mild TBI patients with follow-up neuropsychological assessment in those with complaints and a normal non-contrast CT. Neuropsychological tests comprised the 15 Words test Immediate Recall, Trailmaking test part B, Zoo Map test and the FEEST, which were dichotomized into normal and abnormal. Perfusion CT results of patients with normal neuropsychological test scores were compared to those with abnormal test scores. In total eighteen patients were included. Those with an abnormal score on the Zoo Map test had a significant lower CBV in the right frontal and the bilateral parieto-temporal white matter. Patients with an abnormal score on the FEEST had a significant higher MTT in the bilateral frontal white matter and a significant decreased CBF in the left parieto-temporal grey matter. No significant relation between the perfusion CT parameters and the 15 Words test and the Trailmaking test part B was present. In conclusion, impairments in executive functioning and emotion perception assessed with neuropsychological tests during follow up were related to differences in cerebral perfusion at admission in mild TBI. The pathophysiological concept of these findings is discussed. PMID:24556319

  5. 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.

  6. ROI for outlining an entire tumor is a reliable approach for quantification of lung cancer tumor vascular parameters using CT perfusion

    PubMed Central

    Ma, Ensen; Ren, An; Gao, Baoxiang; Yang, Minxing; Zhao, Qichao; Wang, Wu; Li, Kefeng

    2016-01-01

    Objective To investigate the effect of position and size of tumor region of interest (ROI) on the estimation of lung cancer vascular parameters using 256-slice computed tomography (CT) perfusion. Methods After institutional review board approval and written informed consent, 16 men and 11 women with lung cancer were enrolled in this CT perfusion study. Perfusion, blood volume, and peak enhancement were determined for 60 or 120 mm2 circular ROIs placed at the edge, center, and around (outlining) the visible tumor. Average values were obtained by performing ROI analysis twice by the same observers without any procedural changes. Results Perfusion, blood volume, and peak enhancement measurements were substantially higher at the edge than at the center for both 60 and 120 mm2 ROIs (all P<0.05). Measurements varied substantially depending on the ROI size. Perfusion, blood volume, and peak enhancement for the ROIs outlining tumor were intermediate between those at the tumor edge and center. There were significant correlations between median values and interquartile ranges as follows; perfusion (12.51 [7.91–28.10] mL⋅min−1⋅100 mL−1), blood volume (29.31 [21.82–37.65] mL⋅100 g−1), peak enhancement (12.93 [2.42–22.50]) for the ROIs outlining the tumor, and microvascular density ([19.43±8.78] vessels/0.74 mm2), respectively (r values were 0.732, 0.590, and 0.544 respectively, all P<0.05). Conclusion Spatial and size selection of ROI significantly affects CT perfusion analysis. ROI outlining of entire tumor provides efficient and reliable measurements for clinical assessment of lung cancer using CT perfusion. PMID:27175083

  7. Extracellular Vesicles in Brain Tumor Progression.

    PubMed

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

    2016-04-01

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

  8. Brain perfusion SPECT with Brodmann areas analysis in differentiating frontotemporal dementia subtypes.

    PubMed

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Kapsalaki, Eftychia; Fezoulidis, Ioannis; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2014-01-01

    Despite the known validity of clinical diagnostic criteria, significant overlap of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in several cases, resulting in great uncertainty of the diagnostic boundaries. We evaluated the perfusion between FTD subtypes using brain perfusion (99m)Tc-HMPAO SPECT with Brodmann areas (BA) mapping. NeuroGam software was applied on single photon emission computed tomographic (SPECT) studies for the semi-quantitative evaluation of perfusion in BA and the comparison with the software's normal database. We studied 91 consecutive FTD patients: 21 with behavioural variants (bvFTD), 39 with language variants (lvFTD) [12 with progressive non-fluent aphasia (PNFA), 27 with semantic dementia (SD)], and 31 patients with progressive supranuclear palsy (PSP)/corticobasal degeneration (CBD). Stepwise logistic regression analyses showed that the BA 28L and 32R could independently differentiate bvFTD from lvFTD, while the BA 8R and 25R could discriminate bvFTD from SD and PNFA, respectively. Additionally, BA 7R and 32R were found to discriminate bvFTD from CBD/PSP. The only BA that could differentiate SD from PNFA was 6L. BA 6R and 20L were found to independently differentiate CBD/PSP from lvFTD. Moreover, BA 20L and 22R could discriminate CBD/PSP from PNFA, while BA 6R, 20L and 45R were found to independently discriminate CBD/PSP from SD. Brain perfusion SPECT with BA mapping can be a useful additional tool in differentiating FTD variants by improving the definition of brain areas that are specifically implicated, resulting in a more accurate differential diagnosis in atypical or uncertain forms of FTD. PMID:25387340

  9. Four dimensional optoacoustic imaging of perfusion in preclinical breast tumor model in vivo (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Deán-Ben, Xosé Luís.; Ermolayev, Vladimir; Mandal, Subhamoy; Ntziachristos, Vasilis; Razansky, Daniel

    2016-03-01

    Imaging plays an increasingly important role in clinical management and preclinical studies of cancer. Application of optical molecular imaging technologies, in combination with highly specific contrast agent approaches, eminently contributed to understanding of functional and histological properties of tumors and anticancer therapies. Yet, optical imaging exhibits deterioration in spatial resolution and other performance metrics due to light scattering in deep living tissues. High resolution molecular imaging at the whole-organ or whole-body scale may therefore bring additional understanding of vascular networks, blood perfusion and microenvironment gradients of malignancies. In this work, we constructed a volumetric multispectral optoacoustic tomography (vMSOT) scanner for cancer imaging in preclinical models and explored its capacity for real-time 3D intravital imaging of whole breast cancer allografts in mice. Intrinsic tissue properties, such as blood oxygenation gradients, along with the distribution of externally administered liposomes carrying clinically-approved indocyanine green dye (lipo-ICG) were visualized in order to study vascularization, probe penetration and extravasation kinetics in different regions of interest within solid tumors. The use of v-MSOT along with the application of volumetric image analysis and perfusion tracking tools for studies of pathophysiological processes within microenvironment gradients of solid tumors demonstrated superior volumetric imaging system performance with sustained competitive resolution and imaging depth suitable for investigations in preclinical cancer models.

  10. 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

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

    PubMed

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

    2015-03-01

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

  12. Parametric investigation of heating due to magnetic fluid hyperthermia in a tumor with blood perfusion

    NASA Astrophysics Data System (ADS)

    Liangruksa, Monrudee; Ganguly, Ranjan; Puri, Ishwar K.

    2011-03-01

    Magnetic fluid hyperthermia (MFH) is a cancer treatment that can selectively elevate the tumor temperature without significantly damaging the surrounding healthy tissue. Optimal MFH design requires a fundamental parametric investigation of the heating of soft materials by magnetic fluids. We model the problem of a spherical tumor and its surrounding healthy tissue that are heated by exciting a homogeneous dispersion of magnetic nanoparticles infused only into the tumor with an external AC magnetic field. The key dimensionless parameters influencing thermotherapy are the Péclet, Fourier, and Joule numbers. Analytical solutions for transient and steady hyperthermia provide correlations between these parameters and the portions of tumor and healthy tissue that are subjected to a threshold temperature beyond which they are damaged. Increasing the ratio of the Fourier and Joule numbers also increases the tumor temperature, but doing so can damage the healthy tissue. Higher magnetic heating is required for larger Péclet numbers due to the larger convection heat loss that occurs through blood perfusion. A comparison of the model predictions with previous experimental data for MFH applied to rabbit tumors shows good agreement. The optimal MFH conditions are identified based on two indices, the fraction IT of the tumor volume in which the local temperature is above a threshold temperature and the ratio IN of the damaged normal tissue volume to the tumor tissue volume that also lies above it. The spatial variation in the nanoparticle concentration is also considered. A Gaussian distribution provides efficacy while minimizing the possibility of generating a tumor hot spot. Varying the thermal properties of tumor and normal tissue alters ITand IN but the nature of the temperature distribution remains unchanged.

  13. Adenoviral virotherapy for malignant brain tumors

    PubMed Central

    Nandi, Suvobroto; Lesniak, Maciej S

    2009-01-01

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

  14. Adenoviral virotherapy for malignant brain tumors.

    PubMed

    Nandi, Suvobroto; Lesniak, Maciej S

    2009-06-01

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

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

    SciTech Connect

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

    1988-01-01

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

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

    PubMed Central

    2012-01-01

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

  17. Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

    PubMed Central

    Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

    2015-01-01

    Background Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Methods Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. Results During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Conclusions Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness. PMID:26241047

  18. 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

  19. Perfusion deficits in patients with mild traumatic brain injury characterized by dynamic susceptibility contrast MRI.

    PubMed

    Liu, Wei; Wang, Binquan; Wolfowitz, Rachel; Yeh, Ping-Hong; Nathan, Dominic E; Graner, John; Tang, Haiying; Pan, Hai; Harper, Jamie; Pham, Dzung; Oakes, Terrence R; French, Louis M; Riedy, Gerard

    2013-06-01

    Perfusion deficits in patients with mild traumatic brain injury (TBI) from a military population were characterized by dynamic susceptibility contrast perfusion imaging. Relative cerebral blood flow (rCBF) was calculated by a model-independent deconvolution approach from the tracer concentration curves following a bolus injection of gadolinium diethylenetriaminepentaacetate (Gd-DTPA) using both manually and automatically selected arterial input functions (AIFs). Linear regression analysis of the mean values of rCBF from selected regions of interest showed a very good agreement between the two approaches, with a regression coefficient of R = 0.88 and a slope of 0.88. The Bland-Altman plot also illustrated the good agreement between the two approaches, with a mean difference of 0.6 ± 12.4 mL/100 g/min. Voxelwise analysis of rCBF maps from both approaches demonstrated multiple clusters of decreased perfusion (p < 0.01) in the cerebellum, cuneus, cingulate and temporal gyrus in the group with mild TBI relative to the controls. MRI perfusion deficits in the cerebellum and anterior cingulate also correlated (p < 0.01) with neurocognitive results, including the mean reaction time in the Automated Neuropsychological Assessment Metrics and commission error and detection T-scores in the Continuous Performance Test, as well as neurobehavioral scores in the Post-traumatic Stress Disorder Checklist-Civilian Version. In conclusion, rCBF calculated using AIFs selected from an automated approach demonstrated a good agreement with the corresponding results using manually selected AIFs. Group analysis of patients with mild TBI from a military population demonstrated scattered perfusion deficits, which showed significant correlations with measures of verbal memory, speed of reaction time and self-report of stress symptoms. PMID:23456696

  20. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    Akimoto, Jiro

    2016-04-15

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

  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. 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

  3. 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.

  4. Interleukin-1β induces the upregulation of caveolin-1 expression in a rat brain tumor model

    PubMed Central

    QIN, LI-JUAN; JIA, YONG-SEN; ZHANG, YI-BING; WANG, YIN-HUAN

    2016-01-01

    The aim of the present study was to investigate the expression of caveolin-1 in rat brain glioma tissue, and to determine whether interleukin-1β (IL-1β) has a role in this process. Using glioma cells, a tumor-burdened rat model was established, and the expression of caveolin-1 protein in the tumor sites was significantly increased following intracarotid infusion of IL-1β (3.7 ng/kg/min), as indicated by western blot analysis. The maximum value of the caveolin-1 expression was observed in tumor-burdened rats after 60 min of IL-1β perfusion, and which was significantly enhanced by vascular endothelial growth factor (VEGF). In addition, VEGF also significantly increased IL-1β-induced blood tumor barrier (BTB) permeability. The results suggest that the IL-1β-induced BTB permeability increase may be associated with the expression of caveolin-1 protein, and VEGF may be involved in this process. PMID:27073627

  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. Intraoperative MRI in pediatric brain tumors.

    PubMed

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

    2015-09-01

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

  7. Well plate-based perfusion culture device for tissue and tumor microenvironment replication.

    PubMed

    Zhang, W; Gu, Y; Hao, Y; Sun, Q; Konior, K; Wang, H; Zilberberg, J; Lee, W Y

    2015-07-01

    There are significant challenges in developing in vitro human tissue and tumor models that can be used to support new drug development and evaluate personalized therapeutics. The challenges include: (1) working with primary cells which are often difficult to maintain ex vivo, (2) mimicking native microenvironments from which primary cells are harvested, and (3) the lack of culture devices that can support these microenvironments to evaluate drug responses in a high-throughput manner. Here we report a versatile well plate-based perfusion culture device that was designed, fabricated and used to: (1) ascertain the role of perfusion in facilitating the expansion of human multiple myeloma cells and evaluate drug response of the cells, (2) preserve the physiological phenotype of primary murine osteocytes by reconstructing the 3D cellular network of osteocytes, and (3) circulate primary murine T cells through a layer of primary murine intestine epithelial cells to recapitulate the interaction of the immune cells with the epithelial cells. Through these diverse case studies, we demonstrate the device's design features to support: (1) the convenient and spatiotemporal placement of cells and biomaterials into the culture wells of the device; (2) the replication of tissues and tumor microenvironments using perfusion, stromal cells, and/or biomaterials; (3) the circulation of non-adherent cells through the culture chambers; and (4) conventional tissue and cell characterization by plate reading, histology, and flow cytometry. Future challenges are identified and discussed from the perspective of manufacturing the device and making its operation for routine and wide use. PMID:26021852

  8. Multifunctional nanoparticles for brain tumor imaging and therapy.

    PubMed

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

    2014-02-01

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

  9. 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

  10. Correlation of Intra-Tumor 18F-FDG Uptake Heterogeneity Indices with Perfusion CT Derived Parameters in Colorectal Cancer

    PubMed Central

    Tixier, Florent; Groves, Ashley M.; Goh, Vicky; Hatt, Mathieu; Ingrand, Pierre; Le Rest, Catherine Cheze; Visvikis, Dimitris

    2014-01-01

    Application of textural features analysis to 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) images has been used to characterize intra-tumor uptake heterogeneity and has been shown to reflect disease outcome. A current hypothesis is that 18F-FDG uptake heterogeneity may reflect the physiological tracer uptake related to tumor perfusion. The purpose of our study was to investigate the correlations between intra-tumor uptake heterogeneity and vascular parameters derived from dynamic contrast enhanced (DCE) computed tomography (CT) obtained from an integrated 18F-FDG PET/perfusion CT examination. Methods Thirty patients with proven colorectal cancer prospectively underwent integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT blood flow parametric maps and PET images were analyzed. Correlations between PET heterogeneity and perfusion CT were assessed by Spearman's rank correlation analysis. Results Blood flow visualization provided by DCE-CT images was significantly correlated with 18F-FDG PET metabolically active tumor volume as well as with uptake heterogeneity for patients with stage III/IV tumors (|ρ|:0.66 to 0.78; p-value<0.02). Conclusion The positive correlation found with tumor blood flow indicates that intra-tumor heterogeneity of 18F-FDG PET accumulation reflects to some extent tracer distribution and consequently indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with physiological processes such as tumor vascularization. PMID:24926986

  11. Involvement of tumor acidification in brain cancer pathophysiology

    PubMed Central

    Honasoge, Avinash; Sontheimer, Harald

    2013-01-01

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

  12. Decreased Brain and Placental Perfusion in Omphalopagus Conjoined Twins on Fetal MRI.

    PubMed

    Gorkem, Sureyya Burcu; Kutuk, Mehmet Serdar; Doganay, Selim; Gunes, Tamer; Yildiz, Karamehmet; Kucukaydin, Mustafa

    2016-01-01

    The aim of this study is to evaluate perfusional changes in brain and placenta of omphalopagus conjoined twins and to compare them with singleton fetuses by using diffusion weighted imaging and apparent diffusion coefficient. Fetal MRIs of 28-week-old omphalopagus conjoined twins with a shared liver with two separate gallbladders and portal and hepatic venous systems and three singleton fetuses with unilateral borderline ventriculomegaly at the same gestational week as control group were enrolled retrospectively. There was a significant decrease in ADC values of brain regions (p = 0.018) and placenta (p = 0.005) of conjoined twins compared to the control group. The decreased ADC values in placenta and brain regions in conjoined twins might be due to decreased placental perfusion compared to singleton pregnancy. Our results would be a keystone for future studies which will compare larger group of monochorionic multiple pregnancies with singleton pregnancies. PMID:27034830

  13. Decreased Brain and Placental Perfusion in Omphalopagus Conjoined Twins on Fetal MRI

    PubMed Central

    Kutuk, Mehmet Serdar; Doganay, Selim; Gunes, Tamer; Yildiz, Karamehmet; Kucukaydin, Mustafa

    2016-01-01

    The aim of this study is to evaluate perfusional changes in brain and placenta of omphalopagus conjoined twins and to compare them with singleton fetuses by using diffusion weighted imaging and apparent diffusion coefficient. Fetal MRIs of 28-week-old omphalopagus conjoined twins with a shared liver with two separate gallbladders and portal and hepatic venous systems and three singleton fetuses with unilateral borderline ventriculomegaly at the same gestational week as control group were enrolled retrospectively. There was a significant decrease in ADC values of brain regions (p = 0.018) and placenta (p = 0.005) of conjoined twins compared to the control group. The decreased ADC values in placenta and brain regions in conjoined twins might be due to decreased placental perfusion compared to singleton pregnancy. Our results would be a keystone for future studies which will compare larger group of monochorionic multiple pregnancies with singleton pregnancies. PMID:27034830

  14. SPECT brain perfusion imaging with Tc-99m ECD: Semi-quantitative regional analysis and database mapping

    SciTech Connect

    Schiepers, C.; Hegge, J.; De Roo, M.

    1994-05-01

    Brain SPECT is a well accepted method for the assessment of brain perfusion in various disorders such as epilepsy, stroke, dementia. A program for handling the tomographic data was developed, using a commercial spreadsheet (Microsoft EXCEL) with a set of macro`s for analysis, graphic display and database management of the final results.

  15. Perfusion parameters as potential imaging biomarkers for the early prediction of radiotherapy response in a rat tumor model

    PubMed Central

    Lee, Ho Yun; Kim, Namkug; Goo, Jin Mo; Chie, Eui Kyu; Song, Hye Jong

    2016-01-01

    PURPOSE We aimed to compare various tumor-related radiologic morphometric changes and computed tomography (CT) perfusion parameters before and after treatment, and to determine the optimal imaging assessment technique for the prediction of early response in a rat tumor model treated with radiotherapy. METHODS Among paired tumors of FN13762 murine breast cancer cells implanted bilaterally in the necks of eight Fischer rats, tumors on the right side were treated with a single 20 Gy dose of radiotherapy. Perfusion CT studies were performed on day 0 before radiotherapy, and on days 1 and 5 after radiotherapy. Variables based on the size, including the longest diameter, tumor area, and volume, were measured. Quantitative perfusion analysis was performed for the whole tumor volume and permeabilities and blood volumes (BVs) were obtained. The area under the curve (AUC) difference in the histograms of perfusion parameters and texture analyses of uniformity and entropy were quantified. Apoptotic cell density was measured on pathology specimens immediately after perfusion imaging on day 5. RESULTS On day 1 after radiotherapy, differences in size between the irradiated and nonirradiated tumors were not significant. In terms of percent changes in the uniformity of permeabilities between tumors before irradiation and on day 1 after radiotherapy, the changes were significantly higher in the irradiated tumors than in the nonirradiated tumors (0.085 [−0.417, 0.331] vs. −0.131 [−0.536, 0.261], respectively; P = 0.042). The differences in AUCs of the histogram of voxel-by-voxel vascular permeability and BV in tumors between day 0 and day 1 were significantly higher in treated tumors compared with the control group (permeability, 21.4 [−2.2, 37.5] vs. 9.5 [−8.9, 33.8], respectively, P = 0.030; BV, 52.9 [−6186.0, 419.2] vs. 11.9 [−198.3, 346.7], respectively, P = 0.049). Apoptotic cell density showed a significantly positive correlation with the AUC difference of BV, the

  16. Chemotherapy for malignant brain tumors of childhood

    PubMed Central

    Gottardo, Nicholas G.; Gajjar, Amar

    2009-01-01

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

  17. Estimation of Radiation Exposure of 128-Slice 4D-Perfusion CT for the Assessment of Tumor Vascularity

    PubMed Central

    Horger, Marius; Buchgeister, Markus; Fenchel, Michael; Thomas, Christoph; Boehringer, Nadine; Schulze, Maximilian; Tsiflikas, Ilias; Claussen, Claus D.; Heuschmid, Martin

    2010-01-01

    Objective We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity. Materials and Methods An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D-Perfusion-CT. Phantom measurements were performed on a 128-slice single-source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs). Results Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively. Conclusion Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans. PMID:20808699

  18. 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.

  19. Anger camera imaging of perfused and nonperfused brain tissue with intra-arterial 133Xenon technique.

    PubMed

    Guldberg, C; Karle, A; Jørgensen, P B

    1977-12-30

    The regional cerebral blood flow, the regional blood flow distribution, and the regional distribution of perfused (= vital) brain tissue been imaged with a digitalized conventional Anger camer. An analog scaler was placed behind the PM-tubes to reduce dead-time loss. The input pulse rate was doubled to counteract the effect of scaling on counting statistics, and the gamma emission was filtered through 1 mm of brass to increase the fraction of the integral count rate within the 40% window. In this way the 31 keV peak disappears, and Compton scatter and disturbing coincidences are markedly reduced. This improves spatial resolution. The flow parameters are imaged regionally in 3 X 3 mm2 matrix elements after flat field correction and smoothing. The matrix is 64 X 64 interpolated to 128 X 128. Patient studies emphasized the importance of imaging the distribution of perfused and nonperfused tissue in cases of infarctions, dilacerations, etc., where angiography and conventional brain scanning may often be negative. PMID:415863

  20. Erythropoietin improves the accumulation and therapeutic effects of carboplatin by enhancing tumor vascularization and perfusion.

    PubMed

    Doleschel, Dennis; Rix, Anne; Arns, Susanne; Palmowski, Karin; Gremse, Felix; Merkle, Ruth; Salopiata, Florian; Klingmüller, Ursula; Jarsch, Michael; Kiessling, Fabian; Lederle, Wiltrud

    2015-01-01

    Recombinant human erythropoietin (rhuEpo) is currently under debate for the treatment of chemotherapy-induced anemia due to clinical trials showing adverse effects in Epo-treated patients and the discovery of the erythropoietin-receptor (EpoR) in tumor and endothelial cells. Here, using Epo-Cy5.5 as theranostic near-infrared fluorescent probe we analyzed the effects of rhuEpo as co-medication to carboplatin in non-small-cell-lung-cancer (NSCLC)-xenografts with different tumor cell EpoR-expression (H838 ~8-fold higher than A549). Nude mice bearing subcutaneous A549 and H838 NSCLC-xenografts received either only carboplatin or carboplatin and co-medication of rhuEpo in two different doses. Tumor sizes and relative blood volumes (rBV) were longitudinally measured by 3D-contrast-enhanced ultrasound (3D-US). Tumoral EpoR-levels were determined by combined fluorescence molecular tomography (FMT)/ micro computed tomography (µCT) hybrid imaging. We found that rhuEpo predominantly acted on the tumor endothelium. In both xenografts, rhuEpo co-medication significantly increased vessel densities, diameters and the amount of perfused vessels. Accordingly, rhuEpo induced EpoR-phoshorylation and stimulated proliferation of endothelial cells. However, compared with solely carboplatin-treated tumors, tumor growth was significantly slower in the groups co-medicated with rhuEpo. This is explained by the Epo-mediated vascular remodeling leading to improved drug delivery as obvious by a more than 2-fold higher carboplatin accumulation and significantly enhanced tumor apoptosis. In addition, co-medication of rhuEpo reduced tumor hypoxia and diminished intratumoral EpoR-levels which continuously increased during carboplatin (Cp) -treatment. These findings suggest that co-medication of rhuEpo in well balanced doses can be used to improve the accumulation of anticancer drugs. Doses and indications may be personalized and refined using theranostic EpoR-probes. PMID:26000061

  1. Erythropoietin Improves the Accumulation and Therapeutic Effects of Carboplatin by Enhancing Tumor Vascularization and Perfusion

    PubMed Central

    Doleschel, Dennis; Rix, Anne; Arns, Susanne; Palmowski, Karin; Gremse, Felix; Merkle, Ruth; Salopiata, Florian; Klingmüller, Ursula; Jarsch, Michael; Kiessling, Fabian; Lederle, Wiltrud

    2015-01-01

    Recombinant human erythropoietin (rhuEpo) is currently under debate for the treatment of chemotherapy-induced anemia due to clinical trials showing adverse effects in Epo-treated patients and the discovery of the erythropoietin-receptor (EpoR) in tumor and endothelial cells. Here, using Epo-Cy5.5 as theranostic near-infrared fluorescent probe we analyzed the effects of rhuEpo as co-medication to carboplatin in non-small-cell-lung-cancer (NSCLC)-xenografts with different tumor cell EpoR-expression (H838 ~8-fold higher than A549). Nude mice bearing subcutaneous A549 and H838 NSCLC-xenografts received either only carboplatin or carboplatin and co-medication of rhuEpo in two different doses. Tumor sizes and relative blood volumes (rBV) were longitudinally measured by 3D-contrast-enhanced ultrasound (3D-US). Tumoral EpoR-levels were determined by combined fluorescence molecular tomography (FMT)/ micro computed tomography (µCT) hybrid imaging. We found that rhuEpo predominantly acted on the tumor endothelium. In both xenografts, rhuEpo co-medication significantly increased vessel densities, diameters and the amount of perfused vessels. Accordingly, rhuEpo induced EpoR-phoshorylation and stimulated proliferation of endothelial cells. However, compared with solely carboplatin-treated tumors, tumor growth was significantly slower in the groups co-medicated with rhuEpo. This is explained by the Epo-mediated vascular remodeling leading to improved drug delivery as obvious by a more than 2-fold higher carboplatin accumulation and significantly enhanced tumor apoptosis. In addition, co-medication of rhuEpo reduced tumor hypoxia and diminished intratumoral EpoR-levels which continuously increased during carboplatin (Cp) -treatment. These findings suggest that co-medication of rhuEpo in well balanced doses can be used to improve the accumulation of anticancer drugs. Doses and indications may be personalized and refined using theranostic EpoR-probes. PMID:26000061

  2. Targeting endothelial connexin40 inhibits tumor growth by reducing angiogenesis and improving vessel perfusion.

    PubMed

    Alonso, Florian; Domingos-Pereira, Sonia; Le Gal, Loïc; Derré, Laurent; Meda, Paolo; Jichlinski, Patrice; Nardelli-Haefliger, Denise; Haefliger, Jacques-Antoine

    2016-03-22

    Endothelial connexin40 (Cx40) contributes to regulate the structure and function of vessels. We have examined whether the protein also modulates the altered growth of vessels in tumor models established in control mice (WT), mice lacking Cx40 (Cx40-/-), and mice expressing the protein solely in endothelial cells (Tie2-Cx40). Tumoral angiogenesis and growth were reduced, whereas vessel perfusion, smooth muscle cell (SMC) coverage and animal survival were increased in Cx40-/- but not Tie2-Cx40 mice, revealing a critical involvement of endothelial Cx40 in transformed tissues independently of the hypertensive status of Cx40-/- mice. As a result, Cx40-/- mice bearing tumors survived significantly longer than corresponding controls, including after a cytotoxic administration. Comparable observations were made in WT mice injected with a peptide targeting Cx40, supporting the Cx40 involvement. This involvement was further confirmed in the absence of Cx40 or by peptide-inhibition of this connexin in aorta-sprouting, matrigel plug and SMC migration assays, and associated with a decreased expression of the phosphorylated form of endothelial nitric oxide synthase. The data identify Cx40 as a potential novel target in cancer treatment. PMID:26883111

  3. Targeting endothelial connexin40 inhibits tumor growth by reducing angiogenesis and improving vessel perfusion

    PubMed Central

    Alonso, Florian; Domingos-Pereira, Sonia; Le Gal, Loïc; Derré, Laurent; Meda, Paolo; Jichlinski, Patrice; Nardelli-Haefliger, Denise; Haefliger, Jacques-Antoine

    2016-01-01

    Endothelial connexin40 (Cx40) contributes to regulate the structure and function of vessels. We have examined whether the protein also modulates the altered growth of vessels in tumor models established in control mice (WT), mice lacking Cx40 (Cx40−/−), and mice expressing the protein solely in endothelial cells (Tie2-Cx40). Tumoral angiogenesis and growth were reduced, whereas vessel perfusion, smooth muscle cell (SMC) coverage and animal survival were increased in Cx40−/− but not Tie2-Cx40 mice, revealing a critical involvement of endothelial Cx40 in transformed tissues independently of the hypertensive status of Cx40−/− mice. As a result, Cx40−/− mice bearing tumors survived significantly longer than corresponding controls, including after a cytotoxic administration. Comparable observations were made in WT mice injected with a peptide targeting Cx40, supporting the Cx40 involvement. This involvement was further confirmed in the absence of Cx40 or by peptide-inhibition of this connexin in aorta-sprouting, matrigel plug and SMC migration assays, and associated with a decreased expression of the phosphorylated form of endothelial nitric oxide synthase. The data identify Cx40 as a potential novel target in cancer treatment. PMID:26883111

  4. Analysis of perfusion, microcirculation and drug transport in tumors. A computational study.

    NASA Astrophysics Data System (ADS)

    Zunino, Paolo; Cattaneo, Laura

    2013-11-01

    We address blood flow through a network of capillaries surrounded by a porous interstitium. We develop a computational model based on the Immersed Boundary method [C. S. Peskin. Acta Numer. 2002.]. The advantage of such an approach relies in its efficiency, because it does not need a full description of the real geometry allowing for a large economy of memory and CPU time and it facilitates handling fully realistic vascular networks [L. Cattaneo and P. Zunino. Technical report, MOX, Department of Mathematics, Politecnico di Milano, 2013.]. The analysis of perfusion and drug release in vascularized tumors is a relevant application of such techniques. Blood vessels in tumors are substantially leakier than in healthy tissue and they are tortuous. These vascular abnormalities lead to an impaired blood supply and abnormal tumor microenvironment characterized by hypoxia and elevated interstitial fluid pressure that reduces the distribution of drugs through advection [L.T. Baxter and R.K. Jain. Microvascular Research, 1989]. Finally, we discuss the application of the model to deliver nanoparticles. In particular, transport of nanoparticles in the vessels network, their adhesion to the vessel wall and the drug release in the surrounding tissue will be addressed.

  5. 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

  6. 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

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

    PubMed

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  9. Current concepts of optimal cerebral perfusion pressure in traumatic brain injury

    PubMed Central

    Prabhakar, Hemanshu; Sandhu, Kavita; Bhagat, Hemant; Durga, Padmaja; Chawla, Rajiv

    2014-01-01

    Traumatic brain injury (TBI) consists of varied pathophysiological consequences and alteration of intracranial dynamics, reduction of the cerebral blood flow and oxygenation. In the past decade more emphasis has been directed towards optimizing cerebral perfusion pressure (CPP) in patients who have suffered TBI. Injured brain may show signs of ischemia if CPP remains below 50 mmHg and raising the CPP above 60 mmHg may avoid cerebral oxygen desaturation. Though CPP above 70 mmHg is influential in achieving an improved patient outcome, maintenance of CPP higher than 70 mmHg was associated with greater risk of acute respiratory distress syndrome (ARDS). The target CPP has been laid within 50-70 mmHg. Cerebral blood flow and metabolism are heterogeneous after TBI and with regional temporal differences in the requirement for CPP. Brain monitoring techniques such as jugular venous oximetry, monitoring of brain tissue oxygen tension (PbrO2), and cerebral microdialysis provide complementary and specific information that permits the selection of the optimal CPP. This review highlights the rationale for use CPP directed therapies and neuromonitoring to identify optimal CPP of head injured patients. The article also reviews the evidence provided by various clinical trials regarding optimal CPP and their application in the management of head injured patients. PMID:25190937

  10. An integrated in vitro model of perfused tumor and cardiac tissue

    PubMed Central

    2013-01-01

    Cancer and cardiovascular disease remain the two leading causes of death in the United States. Progress in treatment to reduce morbidity and mortality will include the development of new drugs. Recent advances in induced pluripotent stem cell technology, tissue engineering, and microfabrication techniques have created a unique opportunity to develop three-dimensional (3D) microphysiological systems that more accurately reflect in vivo human biology when compared with two-dimensional flat systems or animal models. Our group is working to develop 3D microphysiological systems using induced pluripotent stem cell technology that simulates the microcirculation, the cardiac muscle, and the solid tumor, and then to combine these systems into an integrated microphysiological system that simulates perfused cardiac muscle and solid tumor on a single platform. The platform will be initially validated to predict anti-cancer efficacy while minimizing cardiac muscle toxicity. A critical feature will be blood flow through a human microcirculation (capillaries and larger microvessels), which is necessary to overcome diffusion limitations of nutrients and waste products in realistic 3D cultures, and serves to integrate multiple organ systems. This is a necessary and critical feature of any platform that seeks to simulate integrated human organ systems. The results of our project should produce a new paradigm for efficient and accurate drug and toxicity screening, initially for anti-cancer drugs with minimal cardiac side effects, and a platform technology that can be eventually used to integrate multiple major organ systems of the human body. PMID:24565445

  11. Novel treatment strategies for brain tumors and metastases

    PubMed Central

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

    2015-01-01

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

  12. Novel treatment strategies for brain tumors and metastases.

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. Radiological Follow-up of a Cerebral Tuberculoma with a Paradoxical Response Mimicking a Brain Tumor

    PubMed Central

    Kim, Jeong-Kwon; Lee, Kyung-Hwa; Kim, Seul-Kee

    2015-01-01

    We report a case of a paradoxical response of a tuberculoma in the brain mimicking a brain tumor. A 76-year-old woman presented with a 2 week history of headache, dysarthia, and orthopnea. Brain magnetic resonance images (MRI) revealed two rim-enhancing lesions on the pons and occipital lobe, and chest computed tomography showed randomly distributed miliary nodules. The tentative diagnosis was tuberculosis (TB) of the brain and lung. She complained of right hemiparesis and worsening general weakness after taking the anti-TB medication. On the monthly follow-up images, the enhanced lesions were enlarged with increased perfusion and choline/creatinine ratio, suggesting a high grade glioma. A surgical resection was completed to diagnose the occipital lesion, and the tuberculoma was pathologically confirmed by a positive TB-polymerase chain reaction. The anti-TB medication was continued for 13 months. A follow-up MRI showed decreased size of the brain lesions associated with perilesional edema, and the clinical symptoms had improved. Brain tuberculoma could be aggravated mimicking brain malignancy during administration of anti-TB medication. This paradoxical response can be effectively managed by continuing the anti-TB drugs. PMID:25932302

  16. Arterial Spin Labeling Perfusion Study in the Patients with Subacute Mild Traumatic Brain Injury

    PubMed Central

    Lin, Che-Ming; Tseng, Ying-Chi; Hsu, Hui-Ling; Chen, Chi-Jen; Chen, David Yen-Ting; Yan, Feng-Xian; Chiu, Wen-Ta

    2016-01-01

    Background This study uses a MRI technique, three-dimension pulse continuous arterial spin labeling (3D-PCASL), to measure the patient’s cerebral blood flow (CBF) at the subacute stage of mild traumatic brain injury (MTBI) in order to analyze the relationship between cerebral blood flow and neurocognitive deficits. Objective To provide the relationship between cortical CBF and neuropsychological dysfunction for the subacute MTBI patients. Methods After MTBI, perfusion MR imaging technique (3D-PCASL) measures the CBF of MTBI patients (n = 23) within 1 month and that of normal controls (n = 22) to determine the quantity and location of perfusion defect. The correlation between CBF abnormalities and cognitive deficits was elucidated by combining the results of the neuropsychological tests of the patients. Result We observed a substantial reduction in CBF in the bilateral frontal and left occipital cortex as compared with the normal persons. In addition, there were correlation between post concussive symptoms (including dizziness and simulator sickness) and CBF in the hypoperfused areas. The more severe symptom was correlated with higher CBF in bilateral frontal and left occipital lobes. Conclusion First, this study determined that despite no significant abnormality detected on conventional CT and MRI studies, hypoperfusion was observed in MTBI group using 3D-PCASL technique in subacute stage, which suggested that this approach may increase sensitivity to MTBI. Second, the correlation between CBF and the severity of post concussive symptoms suggested that changes in cerebral hemodynamics may play a role in pathophysiology underlies the symptoms. PMID:26871696

  17. Stroke prognosis by applying double thresholds on CT-perfusion-brain images

    NASA Astrophysics Data System (ADS)

    Chokchaitam, Somchart; Santipromwong, Nittaya; Muengtaweepongsa, Sombat

    2013-03-01

    The CT-perfusion image shows information of brain abnormalities such as its size and location. Generally, neurologist diagnoses stroke disease using CT-perfusion images such as Cerebral blood flow (CBF), cerebral blood volume (CBV). In our previous report, we applied threshold technique to divide amount of CBV and CBF into low and high level. Then, their levels are applied to identify normal tissue areas, dead tissue areas (infract core) and blood-cot tissue areas (infract penumbra). However, it's not totally correct, if the same threshold is applied to the whole area (it must depend on size of blood vessel in that area. In this report, we propose double thresholds to divided CBV and CBF into 3 levels: very low, medium and very high levels. Very low and very high levels are definitely implied to bad areas and good areas, respectively. The proposed double thresholds makes stroke prognosis more accurate. The simulation results confirm that our proposed results closed to results defined from neurologist comparing to the conventional results.

  18. 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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-12-01

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

  1. Baseline brain perfusion and brain structure in patients with major depression: a multimodal magnetic resonance imaging study

    PubMed Central

    Vasic, Nenad; Wolf, Nadine D.; Grön, Georg; Sosic-Vasic, Zrinka; Connemann, Bernhard J.; Sambataro, Fabio; von Strombeck, Anna; Lang, Dirk; Otte, Stefanie; Dudek, Manuela; Wolf, Robert C.

    2015-01-01

    Background Abnormal regional cerebral blood flow (rCBF) and grey matter volume have been frequently reported in patients with major depressive disorder (MDD). However, it is unclear to what extent structural and functional change co-occurs in patients with MDD and whether markers of neural activity, such as rCBF, can be predicted by structural change. Methods Using MRI, we investigated resting-state rCBF and brain structure in patients with MDD and healthy controls between July 2008 and January 2013. We acquired perfusion images obtained with continuous arterial spin labelling, used voxel-based morphometry to assess grey matter volume and integrated biological parametric mapping analyses to investigate the impact of brain atrophy on rCBF. Results We included 43 patients and 29 controls in our study. Frontotemporal grey matter volume was reduced in patients compared with controls. In patients, rCBF was reduced in the anterior cingulate and bilateral parahippocampal areas and increased in frontoparietal and striatal regions. These abnormalities were confirmed by analyses with brain volume as a covariate. In patients with MDD there were significant negative correlations between the extent of depressive symptoms and bilateral parahippocampal rCBF. We found a positive correlation between depressive symptoms and rCBF for right middle frontal cortical blood flow. Limitations Medication use in patients has to be considered as a limitation of our study. Conclusion Our data suggest that while changes of cerebral blood flow and brain volume co-occur in patients with MDD, structural change is not sufficient to explain altered neural activity in patients at rest. Abnormal brain structure and function in patients with MDD appear to reflect distinct levels of neuropathology. PMID:26125119

  2. Synthesis and evaluation of p-iodophentermine (IP) as a brain perfusion imaging agent

    SciTech Connect

    Elmaleh, D.R.; Kizuka, H.; Garneau, J.; Brownell, G.L.; Keiss, M.; B-Kovach, M.; Hanson, R.N.; Strauss, H.W.

    1984-01-01

    Recently N-isopropyl-rho-(/sup 123/I)-iodoamphetamine (IMP) has been reported as a potential cerebral perfusion imaging agent for single-photon emission tomography (SPECT). Since addition of a methyl group in the alpha position of amphetamine results in increased lipophilicity and prolonged residence time of the compound in the brain, the authors synthesized and evaluated the biological behaviour of rho-Iodo phenteramine (IP). IP was prepared by diazotization of rho-aminophentermine followed by decomposition of the diazonium salt with KI. Radioiodinated analog was prepared either by the solid-phase isotopic exchange reaction of Mangner et al or by decomposition of the piperidinotrazine derivative with a radiochemical yield of 40-60%. Biodistribution in rats showed that the brain concentration of /sup 131/I-IP was 1.69 +- 0.53, 1.70 +- 0.23 and 1.72 +- 0.11% injected dose/g tissue at 5, 30 and 60 min respectively, after IV injection. The lung uptake was 10.82% ID/g at 5 min and decreased to 7.7% ID/g at 60 min. The thyroid activity was low during the first hour of the study indicating minimal deiodination on the aryl ring. Sequential images of the brains of three dogs after intracarotid injection of /sup 123/I-IP showed localization of activity to one hemisphere of the brain, and clearance of <15% at one hour. In addition, SPECT images revealed more intense localization in the region of gray matter then white matter in the brain.

  3. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism1

    PubMed Central

    Galie, Mirco; Farace, Paolo; Nanni, Cristina; Spinelli, Antonello; Nicolato, Elena; Boschi, Federico; Magnani, Paolo; Trespidi, Silvia; Ambrosini, Valentina; Fanti, Stefano; Merigo, Flavia; Osculati, Francesco; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition. PMID:18030358

  4. Cilengitide in Treating Children With Refractory Primary Brain Tumors

    ClinicalTrials.gov

    2013-09-27

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

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

    PubMed

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

    2015-01-01

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

  6. Partial volume correction of brain perfusion estimates using the inherent signal data of time-resolved arterial spin labeling.

    PubMed

    Ahlgren, André; Wirestam, Ronnie; Petersen, Esben Thade; Ståhlberg, Freddy; Knutsson, Linda

    2014-09-01

    Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross-contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high-resolution T1 -weighted morphological image volume that is coregistered to the low-resolution ASL data, making the result sensitive to errors in the segmentation and coregistration. In this work, we present a methodology for partial volume estimation and correction, using only low-resolution ASL data acquired with the QUASAR sequence. The methodology consists of a T1 -based segmentation method, with no spatial priors, and a modified PVC method based on linear regression. The presented approach thus avoids prior assumptions about the spatial distribution of brain compartments, while also avoiding coregistration between different image volumes. Simulations based on a digital phantom as well as in vivo measurements in 10 volunteers were used to assess the performance of the proposed segmentation approach. The simulation results indicated that QUASAR data can be used for robust partial volume estimation, and this was confirmed by the in vivo experiments. The proposed PVC method yielded probable perfusion maps, comparable to a reference method based on segmentation of a high-resolution morphological scan. Corrected gray matter (GM) perfusion was 47% higher than uncorrected values, suggesting a significant amount of PVEs in the data. Whereas the reference method failed to completely eliminate the dependence of perfusion estimates on the volume fraction, the novel approach produced GM perfusion values independent of GM volume fraction. The intra-subject coefficient of variation of corrected perfusion values was lowest for the proposed PVC method. As shown in this work, low-resolution partial volume estimation in connection with ASL perfusion

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

    PubMed

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

    2016-05-01

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

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

    PubMed

    Gordillo, Nelly; Montseny, Eduard; Sobrevilla, Pilar

    2013-10-01

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

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

    PubMed

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

    2015-01-01

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

  10. Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

    SciTech Connect

    Fokas, Emmanouil; Haenze, Joerg; Kamlah, Florentine; Eul, Bastian G.; Lang, Nico; Keil, Boris; Heverhagen, Johannes T.; Engenhart-Cabillic, Rita; An Hanxiang; Rose, Frank

    2010-08-01

    Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.

  11. Detection of the brain response during a cognitive task using perfusion-based event-related functional MRI.

    PubMed

    Yee, S H; Liu, H L; Hou, J; Pu, Y; Fox, P T; Gao, J H

    2000-08-01

    Event-related (ER) fMRI has evoked great interest due to the ability to depict the dynamic features of human brain function during various cognitive tasks. Thus far, all cognitive ER-fMRI studies have been based on blood oxygenation level-dependent (BOLD) contrast techniques. Compared with BOLD-based fMRI techniques, perfusion-based fMRI is able to localize the region of neuronal activity more accurately. This report demonstrates, for the first time, the detection of the brain response to a cognitive task using high temporal resolution perfusion-based ER-fMRI. An English verb generation task was used in this study. Results show that perfusion-based ER-fMRI accurately depicts the activation in Broca's area. Average changes in regional relative cerebral blood flow reached a maximum value of 30.7% at approximately 6.5 s after the start of stimulation and returned to 10% of the maximum value at approximately 12.8 s. Our results show that perfusion-based ER-fMRI is a useful tool for cognitive neuroscience studies, providing comparable temporal resolution and better localization of brain function than BOLD ER-fMRI. PMID:10943717

  12. 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.

  13. Cortical Plasticity in the Setting of Brain Tumors.

    PubMed

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

    2016-02-01

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

  14. Childhood Brain and Spinal Cord Tumors Treatment Overview

    MedlinePlus

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

  15. Treatment of Newly Diagnosed and Recurrent Childhood Brain Tumors

    MedlinePlus

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

  16. Glial brain tumor detection by using symmetry analysis

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  17. [Assessment of brain perfusion by arterial spin-labeling MR imaging in qusai-moyamoya disease associated with Graves' disease].

    PubMed

    Hayashi, Hisako; Kawatani, Masao; Ohta, Genrei; Kometani, Hiroshi; Ohshima, Yusei

    2014-07-01

    We report a case of 12-year-old girl with Graves' disease who had presented with deterioration in physical and scholastic performances since 10 years of age. She had an episode of atonic seizure and difficulty in speech. Brain MRI revealed formation of moyamoya vessels and a lesion suggestive of ischemic changes in the left frontal lobe. Because of uncontrollable thyrotoxicosis with anti-thyroid drug, she received a subtotal thyroidectomy. Two months later, she received a shunt operation between left superficial temporal artery and middle cerebral artery. The postoperative arterial spin-labeling MR imaging demonstrated an improvement of brain perfusion in left frontal lobe compared with the preoperative one, and provided comparable results of angiography and acetazolamide-challenged 150-gas PET. Thus, arterial spin-labeling MR imaging seems useful for follow-up evaluation of brain perfusion in qusai-moyamoya disease. PMID:25154228

  18. Localized Drug Application and Sub-Second Voltammetric Dopamine Release Measurements in a Brain Slice Perfusion Device

    PubMed Central

    2015-01-01

    The use of fast scan cyclic voltammetry (FSCV) to measure the release and uptake of dopamine (DA) as well as other biogenic molecules in viable brain tissue slices has gained popularity over the last 2 decades. Brain slices have the advantage of maintaining the functional three-dimensional architecture of the neuronal network while also allowing researchers to obtain multiple sets of measurements from a single animal. In this work, we describe a simple, easy-to-fabricate perfusion device designed to focally deliver pharmacological agents to brain slices. The device incorporates a microfluidic channel that runs under the perfusion bath and a microcapillary that supplies fluid from this channel up to the slice. We measured electrically evoked DA release in brain slices before and after the administration of two dopaminergic stimulants, cocaine and GBR-12909. Measurements were collected at two locations, one directly over and the other 500 μm away from the capillary opening. Using this approach, the controlled delivery of drugs to a confined region of the brain slice and the application of this chamber to FSCV measurements, were demonstrated. Moreover, the consumption of drugs was reduced to tens of microliters, which is thousands of times less than traditional perfusion methods. We expect that this simply fabricated device will be useful in providing spatially resolved delivery of drugs with minimum consumption for voltammetric and electrophysiological studies of a variety of biological tissues both in vitro and ex vivo. PMID:24734992

  19. 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

  20. 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 ( ...

  1. 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

  2. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis.

    PubMed

    Zhao, Liya; Jia, Kebin

    2016-01-01

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

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

    PubMed

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

    2014-08-01

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

  4. 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

  5. Hepatic perfusion in a tumor model using DCE-CT: an accuracy and precision study

    NASA Astrophysics Data System (ADS)

    Stewart, Errol E.; Chen, Xiaogang; Hadway, Jennifer; Lee, Ting-Yim

    2008-08-01

    In the current study we investigate the accuracy and precision of hepatic perfusion measurements based on the Johnson and Wilson model with the adiabatic approximation. VX2 carcinoma cells were implanted into the livers of New Zealand white rabbits. Simultaneous dynamic contrast-enhanced computed tomography (DCE-CT) and radiolabeled microsphere studies were performed under steady-state normo-, hyper- and hypo-capnia. The hepatic arterial blood flows (HABF) obtained using both techniques were compared with ANOVA. The precision was assessed by the coefficient of variation (CV). Under normo-capnia the microsphere HABF were 51.9 ± 4.2, 40.7 ± 4.9 and 99.7 ± 6.0 ml min-1 (100 g)-1 while DCE-CT HABF were 50.0 ± 5.7, 37.1 ± 4.5 and 99.8 ± 6.8 ml min-1 (100 g)-1 in normal tissue, tumor core and rim, respectively. There were no significant differences between HABF measurements obtained with both techniques (P > 0.05). Furthermore, a strong correlation was observed between HABF values from both techniques: slope of 0.92 ± 0.05, intercept of 4.62 ± 2.69 ml min-1 (100 g)-1 and R2 = 0.81 ± 0.05 (P < 0.05). The Bland-Altman plot comparing DCE-CT and microsphere HABF measurements gives a mean difference of -0.13 ml min-1 (100 g)-1, which is not significantly different from zero. DCE-CT HABF is precise, with CV of 5.7, 24.9 and 1.4% in the normal tissue, tumor core and rim, respectively. Non-invasive measurement of HABF with DCE-CT is accurate and precise. DCE-CT can be an important extension of CT to assess hepatic function besides morphology in liver diseases.

  6. 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

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

    PubMed Central

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

    2014-01-01

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

  8. A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.

    PubMed

    Xie, Long; Dolui, Sudipto; Das, Sandhitsu R; Stockbower, Grace E; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A; Detre, John A; Wolk, David A

    2016-01-01

    Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease. PMID:27222794

  9. Development of a realistic, dynamic digital brain phantom for CT perfusion validation

    NASA Astrophysics Data System (ADS)

    Divel, Sarah E.; Segars, W. Paul; Christensen, Soren; Wintermark, Max; Lansberg, Maarten G.; Pelc, Norbert J.

    2016-03-01

    Physicians rely on CT Perfusion (CTP) images and quantitative image data, including cerebral blood flow, cerebral blood volume, and bolus arrival delay, to diagnose and treat stroke patients. However, the quantification of these metrics may vary depending on the computational method used. Therefore, we have developed a dynamic and realistic digital brain phantom upon which CTP scans can be simulated based on a set of ground truth scenarios. Building upon the previously developed 4D extended cardiac-torso (XCAT) phantom containing a highly detailed brain model, this work consisted of expanding the intricate vasculature by semi-automatically segmenting existing MRA data and fitting nonuniform rational B-spline surfaces to the new vessels. Using time attenuation curves input by the user as reference, the contrast enhancement in the vessels changes dynamically. At each time point, the iodine concentration in the arteries and veins is calculated from the curves and the material composition of the blood changes to reflect the expected values. CatSim, a CT system simulator, generates simulated data sets of this dynamic digital phantom which can be further analyzed to validate CTP studies and post-processing methods. The development of this dynamic and realistic digital phantom provides a valuable resource with which current uncertainties and controversies surrounding the quantitative computations generated from CTP data can be examined and resolved.

  10. A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment

    PubMed Central

    Xie, Long; Dolui, Sudipto; Das, Sandhitsu R.; Stockbower, Grace E.; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A.; Detre, John A.; Wolk, David A.

    2016-01-01

    Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or “stress test”, may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease. PMID:27222794

  11. Is the solitary dark neuron a manifestation of postmortem trauma to the brain inadequately fixed by perfusion?

    PubMed

    Cammermeyer, J

    1978-06-01

    Dark neurons, classified as solitary because of their sparse occurrence, were discerned in the transitional zones between gray and white matter in various species of laboratory animals fixed by perfusion. These neurons, histologically indistinguishable from dark neurons in immersion fixed material, tended to develop when the saline perfusion was delayed or slow, the amount of the Bouin fixative was excessive, or the autopsy was performed shortly after the perfusion. Under these conditions, the white matter manifested a softer consistency and a paler color than the gray matter. These observations suggest that, as the consequence of regional differences in intensity and speed of fixation, distortion during extraction of the brain may activate a stress force in the transitional zones where incompletely fixed neurons become affected and acquire an abnormal affinity for aniline dyes and silver. PMID:97249

  12. 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.

  13. 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

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

    NASA Astrophysics Data System (ADS)

    Dahal, Sudhir

    ) and healthy tissue with over 99% accuracy. NMPPAS spectral features showed evident differences between tumor and healthy tissues, and ratiometric analysis ensured that only a few wavelengths could be used for excitation instead of using numerous wavelength excitations to create spectra. This process would significantly reduce the analysis time while maintaining the same degree of accuracy. Tissue phantoms were fabricated in order to characterize the properties of NMPPAS. Scattering particles were doped into the phantoms to simulate their light scattering properties to real tissues. This allowed for better control over shape, size, reproducibility and doping in the sample while maintaining the light-tissue interaction properties of real tissue. To make NMPPAS viable for clinical applications, the technique was characterized to determine the spatial (lateral and longitudinal) resolution, depth of penetration and its ability to image in three-dimension through layers of tissue. Both resolutions were determined to be near-cellular level resolution (50-70 microm), obtained initially with the aid of the technique of multiphoton fluorescence, and later verified using NMPPAS imaging. Additionally, the maximum depth of penetration and detection was determined to be about 1.4cm, making the technique extremely suitable to margin tumors from underlying tissues in the brain. The capability of NMPPAS to detect and image layers that lie beneath other structures and blood vessels was also investigated. Three-dimensional images were obtained for the first time using NMPPAS. The images were obtained from different depths and structures were imaged through other layers of existing structures in the sample. This verified that NMPPAS was capable of detecting and imaging structures that lie embedded within the tissues. NMPPAS images of embedded structures were also obtained with the presence of hemoglobin, which is potentially the largest source of background in blood-perfused tissues

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

    PubMed

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

    2009-07-01

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

  16. 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

  17. 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

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

    PubMed

    Karathanasis, Efstathios; Ghaghada, Ketan B

    2016-09-01

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

  19. 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

  20. Evolution of Brain Tumor and Stability of Geometric Invariants

    PubMed Central

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

    2008-01-01

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

  1. 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

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

    PubMed Central

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

    2008-01-01

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

  3. Hemodynamic Segmentation of Brain Perfusion Images with Delay and Dispersion Effects Using an Expectation-Maximization Algorithm

    PubMed Central

    Lu, Chia-Feng; Guo, Wan-Yuo; Chang, Feng-Chi; Huang, Shang-Ran; Chou, Yen-Chun; Wu, Yu-Te

    2013-01-01

    Automatic identification of various perfusion compartments from dynamic susceptibility contrast magnetic resonance brain images can assist in clinical diagnosis and treatment of cerebrovascular diseases. The principle of segmentation methods was based on the clustering of bolus transit-time profiles to discern areas of different tissues. However, the cerebrovascular diseases may result in a delayed and dispersed local perfusion and therefore alter the hemodynamic signal profiles. Assessing the accuracy of the segmentation technique under delayed/dispersed circumstance is critical to accurately evaluate the severity of the vascular disease. In this study, we improved the segmentation method of expectation-maximization algorithm by using the results of hierarchical clustering on whitened perfusion data as initial parameters for a mixture of multivariate Gaussians model. In addition, Monte Carlo simulations were conducted to evaluate the performance of proposed method under different levels of delay, dispersion, and noise of signal profiles in tissue segmentation. The proposed method was used to classify brain tissue types using perfusion data from five normal participants, a patient with unilateral stenosis of the internal carotid artery, and a patient with moyamoya disease. Our results showed that the normal, delayed or dispersed hemodynamics can be well differentiated for patients, and therefore the local arterial input function for impaired tissues can be recognized to minimize the error when estimating the cerebral blood flow. Furthermore, the tissue in the risk of infarct and the tissue with or without the complementary blood supply from the communicating arteries can be identified. PMID:23894386

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

    PubMed Central

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

    2013-01-01

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

  5. 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.

  6. 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.

  7. Longitudinal Changes in Tumor Perfusion Pattern during the Radiation Therapy Course and its Clinical Impact in Cervical Cancer

    SciTech Connect

    Mayr, Nina A.; Wang, Jian Z.; Zhang, Dongqing; Grecula, John C.; Lo, Simon S.; Jaroura, David; Montebello, Joseph; Zhang Hualin; Li, Kaile; Lu, Lanchun; Huang Zhibin; Fowler, Jeffery M.; Wu, Dee H.; Knopp, Michael V.; Yuh, William T.C.

    2010-06-01

    Purpose: To study the temporal changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns during the radiation therapy (RT) course and their influence on local control and survival in cervical cancer. Methods and Materials: DCE-MRI was performed in 98 patients with Stage IB{sub 2}-IVA cervical cancer before RT (pre-RT) and during early RT (20-25 Gy) and mid-RT (45-50 Gy). Signal intensity (SI) from the DCE-MRI time-SI curve was derived for each tumor voxel. The poorly perfused low-DCE tumor subregions were quantified as lower 10th percentiles of SI (SI10). Local control, disease-specific survival, and overall survival were correlated with DCE parameters at pre-RT, early RT, and mid-RT. Median follow-up was 4.9 (range, 0.2-9.0) years. Results: Patients (16/98) with initial pre-RT high DCE (SI10 >=2.1) had 100% 5-year local control, 81% disease-specific survival, and 81% overall survival, compared with only 79%, 61%, and 55%, respectively, in patients with pre-RT low DCE. Conversion from pre-RT low DCE to high DCE in early RT (28/82 patients) was associated with higher local control, disease-specific survival, and overall survival (93%, 74%, and 67%, respectively). In comparison with all other groups, outcome was worst in patients with persistently low DCE from pre-RT throughout the mid-RT phase (66%, 44%, and 43%; p = 0.003, 0.003, and 0.020; respectively). Conclusion: Longitudinal tumor perfusion changes during RT correlate with treatment outcome. Persistently low perfusion in pre-RT, early RT, and mid-RT indicates a high risk of treatment failure, whereas outcome is favorable in patients with initially high perfusion or subsequent improvements of initially low perfusion. These findings likely reflect reoxygenation and may have potential for noninvasive monitoring of intra-treatment radio-responsiveness and for guiding adaptive therapy.

  8. 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

  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. 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.