4,088 research outputs found
The Blood-CSF-Brain Route of Neurological Disease: The Indirect Pathway into the Brain.
Full text linkThe brain is protected by the endothelial blood-brain-barrier (BBB) that limits the access of micro-organisms, tumour cells, immune cells and autoantibodies to the parenchyma. However, the classic model of disease spread across a disrupted BBB does not explain the focal distribution of lesions seen in a variety of neurological diseases and why lesions are frequently adjacent to the cerebrospinal fluid (CSF) spaces. We have critically reviewed the possible role of a blood-CSF-brain route as a disease entry pathway into the brain parenchyma. The initial step of this pathway is the transfer of pathogens or immune components from the blood into the CSF at the choroid plexuses, where the blood-CSF-barrier (BCSFB) is located. The flow of CSF results in disease dissemination throughout the CSF spaces. Access to the brain parenchyma from the CSF, can then occur across the ependymal layer at the ventricular surface, or across the pial-glial barrier of the subarachnoid space and the Virchow-Robin spaces. We have reviewed the anatomy and physiology of the blood-CSF-brain pathway and the brain barriers controlling this process. We then summarised the evidence supporting this brain entry route in a cross-section of neurological diseases including neuromyelitis optica, multiple sclerosis, neurosarcoidosis, neuropsychiatric lupus, cryptococcal infection, and both solid and haematological tumours. This summary highlights the conditions that share the blood-CSF-brain pathway as a pathogenetic mechanism. These include the characteristic proximity of lesions to CSF, evidence of disruption of the brain barriers, and the identification of significant pathology within the CSF. An improved understanding of pathological transfer through the CSF and across all brain barriers will inform on more effective and targeted treatments of primary and secondary disease of the central nervous system
Spectral Analysis of Dynamic PET Studies: A Review of 20 Years of Method Developments and Applications
Full text linkIn Positron Emission Tomography (PET), spectral analysis (SA) allows the quantification of dynamic data by relating the radioactivity measured by the scanner in time to the underlying physiological processes of the system under investigation. Among the different approaches for the quantification of PET data, SA is based on the linear solution of the Laplace transform inversion whereas the measured arterial and tissue time-activity curves of a radiotracer are used to calculate the input response function of the tissue. In the recent years SA has been used with a large number of PET tracers in brain and nonbrain applications, demonstrating that it is a very flexible and robust method for PET data analysis. Differently from the most common PET quantification approaches that adopt standard nonlinear estimation of compartmental models or some linear simplifications, SA can be applied without defining any specific model configuration and has demonstrated very good sensitivity to the underlying kinetics. This characteristic makes it useful as an investigative tool especially for the analysis of novel PET tracers. The purpose of this work is to offer an overview of SA, to discuss advantages and limitations of the methodology, and to inform about its applications in the PET field
Experimental Design and Practical Data Analysis in Positron Emission Tomography
No full textThe book contains all the basic notions of Positron Emission Tomography that span from physiology to radiochemistry, physics, math and statistics. All material was carefully crafted and is now presented in graphical manner to ease reading, studying and browsing. It suits equally undergraduate and graduate academic students but it shall be of interest to clinical fellows or professionals in the biomedical sector that use PET in their activity or develop technologies in the area
TSPO: functions and applications of a mitochondrial stress response pathway
No full textThe mitochondrial outer membrane protein TSPO (translocator protein) lies in a privileged position at the interface between mitochondrion and cytosol. Since the initially discovery, nearly forty years ago, it has generated major interest among various disciplines of modern experimental and applied biomedicine. The focused meeting we have organized aimed at summarizing the state of the art knowledge on TSPO and the discipline-based segregated concepts that have made this an exciting and active field of science. The scientists who have generously contributed the event have agreed to generate a special issue here published—stemmed from the discussion of the vent. This consists in a series of contributions via which the know-how is shared aiming to inspire current and future endeavours to validate and accelerate the impact of TSPO science in human pathophysiology and clinical applications
Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot
Full text linkPET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions.
The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans.
In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade.
We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i.e. there were no significant post-transcriptional changes). This condition can be readily established a priori by assessing the correlation between PET and mRNA expression
Controlling the multiplicity using weighted T-sum statistic.
Full text linkWe introduce a new test procedure for multiple hypothesis testing based on the permutation space of the sum of test-statistics (t-sum). The underlying combining function is shown to be an instance of a family to which it also belongs the well-known combining functions based on the maximum of test-statistics (t-max). After discussing the family-wise error rate and the false discovery rate, two common approaches to the control of the type I error in multiple testing, we consider two further error rates, the stochastic family error and the mean square error model fit estimator. By means of a two large set of simulations we shoe that besides controlling the family-wise error rate the weak sense, the t-sum procedure also controls the stochastic family error and could considerably outperform the t-max procedure in power and mean square error in experiments with low degrees of freedom. They are also shown several circumstances in which it fits the model better than a procedure controlling the false discovery rate and even better of simply performing a series of univariate tests, which do not control any errors. The t-sum procedure is suitable for pilot and exploratory studies in neuroimaging and in other experimental contexts in which the sample size/number of hypotheses ratio is low, the data correlation is moderate, and the proportion of false hypothesis is possibly large. We end the discussion outlining possible investigations of the more general form of combining function (weighted sum) with the aim of data-driven selection of an optimal poewer combining function
Milano consolato nell' elettione a questo arciuescouado, e promotione alla sagra porpora dell' eminentissimo Federico Visconti : colla sua solennissima entrata seguita a' 11. genaro 1682 e fontioni antecedenti /
No full textFrontispiece coat of arms of Milan, engraved by Federico Agnelli.Signatures: pi⁴ A-G⁴ H⁴(-H4).Mode of access: Internet.Binding: limp vellum. Author & title written on spine
sj-pdf-1-jcb-10.1177_0271678X231157958 - Supplemental material for The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats
No full textSupplemental material, sj-pdf-1-jcb-10.1177_0271678X231157958 for The effects of acute Methylene Blue administration on cerebral blood flow and metabolism in humans and rats by Nisha Singh, Eilidh MacNicol, Ottavia DiPasquale, Karen Randall, David Lythgoe, Ndabezinhle Mazibuko, Camilla Simmons, Pierluigi Selvaggi, Stephanie Stephenson, Federico E Turkheimer, Diana Cash, Fernando Zelaya and Alessandro Colasanti in Journal of Cerebral Blood Flow & Metabolism</p
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