scholarly journals Assessment of Regional Differences in Tariquidar-Induced P-Glycoprotein Modulation at the Human Blood–Brain Barrier

2009 ◽  
Vol 30 (3) ◽  
pp. 510-515 ◽  
Author(s):  
Martin Bauer ◽  
Rudolf Karch ◽  
Friederike Neumann ◽  
Claudia C Wagner ◽  
Kurt Kletter ◽  
...  
Keyword(s):  
Regional Differences ◽  
Statistical Parametric Mapping ◽  
Brain Regions ◽  
Parahippocampal Gyrus ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Positron Emission ◽  
Before And After ◽  
Induced Changes ◽  
Pet Scans

We attempted to assess regional differences in cerebral P-glycoprotein (P-gp) function by performing paired positron emission tomography (PET) scans with the P-gp substrate ( R)-[11C]verapamil in five healthy subjects before and after i.v. infusion of tariquidar (2 mg/kg). Comparison of tariquidar-induced changes in distribution volumes ( DVs) in 42 brain regions of interest (ROIs) failed to detect significant differences among brain ROIs. Statistical parametric mapping analysis of parametric DV images visualized symmetrical bilateral clusters with moderately higher DV increases in response to tariquidar administration in cerebellum, parahippocampal gyrus, olfactory gyrus, and middle temporal lobe and cortex, which might reflect moderately decreased P-gp function and expression.

scholarly journals Head to head comparison of (R)-[11C]verapamil and [18F]MC225 in non-human primates, tracers for measuring P-glycoprotein function

2021 ◽  
Author(s):  
Lara Garcia Varela ◽  
David Vállez García ◽  
Pablo Aguiar ◽  
Teratuka Kakiuchi ◽  
Hiroyuki Ohba ◽  
...  
Keyword(s):  
Regional Differences ◽  
Input Function ◽  
Brain Disorders ◽  
Positive Slope ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Tracer Kinetic ◽  
Best Parameter ◽  
Pet Scans

Abstract Purpose P-glycoprotein (P-gp) function is altered in several brain disorders; thus, it is of interest to monitor the P-gp function in vivo using PET. (R)-[11C]verapamil is considered as the gold standard tracer to measure the P-gp function, however, it presents some drawbacks that limit its use. New P-gp tracers have been developed with improved properties, such as [18F]MC225. This study compares the characteristics of (R)-[11C]verapamil and [18F]MC225 in the same subjects. Methods Three non-human primates underwent 4 PET scans: 2 with (R)-[11C]verapamil and 2 with [18F]MC225, at baseline and after P-gp inhibition. The 30-min PET data were analyzed using 1-TCM and metabolite-corrected-plasma as input function. Tracer kinetic parameters at baseline and after-inhibition were compared. Regional differences and simplified methods to quantify the P-gp function were also assessed. Results At baseline, [18F]MC225 VT values were higher and k2 values were lower than those of (R)-[11C]verapamil, whereas K1 values were not significantly different. After-inhibition, VT values of the 2 tracers were similar, however, (R)-[11C]verapamil K1 and k2 values were higher than those of [18F]MC225. Significant regional differences between tracers were found at baseline, which disappeared after inhibition. The positive slope of the SUV-TAC was positively correlated to the K1 and VT of both tracers. Conclusion [18F]MC225 and (R)-[11C]verapamil show comparable sensitivity to measure the P-gp function in non-human primates. Moreover, this study highlights the 30-min VT as the best parameter to measure decreases in the P-gp function with both tracers. [18F]MC225 may become the first radiofluorinated tracer able to measure decreases and increases in the P-gp function due to its higher baseline VT.

scholarly journals Head-to-head comparison of (R)-[11C]verapamil and [18F]MC225 in non-human primates, tracers for measuring P-glycoprotein function

2021 ◽  
Author(s):  
Lara García-Varela ◽  
David Vállez García ◽  
Pablo Aguiar ◽  
Takeharu Kakiuchi ◽  
Hiroyuki Ohba ◽  
...  
Keyword(s):  
Regional Differences ◽  
Compartment Model ◽  
Input Function ◽  
Positive Slope ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Tracer Kinetic ◽  
Best Parameter ◽  
Pet Scans

Abstract Purpose P-glycoprotein (P-gp) function is altered in several brain disorders; thus, it is of interest to monitor the P-gp function in vivo using PET. (R)-[11C]verapamil is considered the gold standard tracer to measure the P-gp function; however, it presents some drawbacks that limit its use. New P-gp tracers have been developed with improved properties, such as [18F]MC225. This study compares the characteristics of (R)-[11C]verapamil and [18F]MC225 in the same subjects. Methods Three non-human primates underwent 4 PET scans: 2 with (R)-[11C]verapamil and 2 with [18F]MC225, at baseline and after P-gp inhibition. The 30-min PET data were analyzed using 1-Tissue Compartment Model (1-TCM) and metabolite-corrected plasma as input function. Tracer kinetic parameters at baseline and after inhibition were compared. Regional differences and simplified methods to quantify the P-gp function were also assessed. Results At baseline, [18F]MC225 VT values were higher, and k2 values were lower than those of (R)-[11C]verapamil, whereas K1 values were not significantly different. After inhibition, VT values of the 2 tracers were similar; however, (R)-[11C]verapamil K1 and k2 values were higher than those of [18F]MC225. Significant regional differences between tracers were found at baseline, which disappeared after inhibition. The positive slope of the SUV-TAC was positively correlated to the K1 and VT of both tracers. Conclusion [18F]MC225 and (R)-[11C]verapamil show comparable sensitivity to measure the P-gp function in non-human primates. Moreover, this study highlights the 30-min VT as the best parameter to measure decreases in the P-gp function with both tracers. [18F]MC225 may become the first radiofluorinated tracer able to measure decreases and increases in the P-gp function due to its higher baseline VT.

scholarly journals PET Scan Perfusion Imaging in the Prader–Willi Syndrome: New Insights into the Psychiatric and Social Disturbances

2010 ◽  
Vol 31 (1) ◽  
pp. 275-282 ◽  
Author(s):  
Carine Mantoulan ◽  
Pierre Payoux ◽  
Gwenaëlle Diene ◽  
Mélanie Glattard ◽  
Bernadette Rogé ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Severe Disabilities ◽  
Brain Regions ◽  
Pet Scan ◽  
Prader Willi Syndrome ◽  
Behavioral Skills ◽  
Positron Emission ◽  
Functional Consequences ◽  
Magnetic Resonance Imaging Mri ◽  
Pet Scans

The Prader–Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H215O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship ( P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals.

Structural and Functional MRI Brain Changes in Patients with Schizophrenia Following Electroconvulsive Therapy: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Yuchao Jiang ◽  
Mingjun Duan ◽  
Hui He ◽  
Dezhong Yao ◽  
Cheng Luo
Keyword(s):  
Systematic Review ◽  
Functional Mri ◽  
Electroconvulsive Therapy ◽  
Brain Regions ◽  
Parahippocampal Gyrus ◽  
Medical Subject Headings ◽  
Therapeutic Mechanisms ◽  
Brain Changes ◽  
Meta Analyses ◽  
Induced Changes

Background: Schizophrenia (SZ) is a severe psychiatric disorder typically characterized by multidimensional psychotic syndromes. Electroconvulsive therapy (ECT) is a treatment option for medication-resistant patients with SZ or to resolve acute symptoms. Although the efficacy of ECT has been demonstrated in clinical use, its therapeutic mechanisms in the brain remain elusive. Objective: This study aimed to summarize brain changes on structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) after ECT. Methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was carried out. The PubMed and Medline databases were systematically searched using the following medical subject headings (MeSH): (electroconvulsive therapy OR ECT) AND (schizophrenia) AND (MRI OR fMRI OR DTI OR DWI). Results: This review yielded 12 MRI studies, including 4 with sMRI, 5 with fMRI and 3 with multimodal MRI. Increases in volumes of the hippocampus and its adjacent regions (parahippocampal gyrus and amygdala) as well as insula and frontotemporal regions were noted after ECT. fMRI studies found ECT-induced changes in different brain regions/networks, including the hippocampus, amygdala, default model network, salience network and other regions/networks that are thought to highly correlate with the pathophysiologic characteristics of SZ. The results of the correlation between brain changes and symptom remissions are inconsistent Conclusion: Our review provides evidence supporting ECT-induced brain changes on sMRI and fMRI in SZ and explores the relationship between these changes and symptom remission.

scholarly journals Population-specific brain [18F]-FDG PET templates of Chinese subjects for statistical parametric mapping

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Hongkai Wang ◽  
Yang Tian ◽  
Yang Liu ◽  
Zhaofeng Chen ◽  
Haoyu Zhai ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Statistical Parametric Mapping ◽  
Brain Regions ◽  
Brain Images ◽  
Parametric Mapping ◽  
Brain Morphometry ◽  
Brain Pet ◽  
Positron Emission ◽  
The Family ◽  
Function Impairment

AbstractStatistical Parametric Mapping (SPM) is a computational approach for analysing functional brain images like Positron Emission Tomography (PET). When performing SPM analysis for different patient populations, brain PET template images representing population-specific brain morphometry and metabolism features are helpful. However, most currently available brain PET templates were constructed using the Caucasian data. To enrich the family of publicly available brain PET templates, we created Chinese-specific template images based on 116 [18F]-fluorodeoxyglucose ([18F]-FDG) PET images of normal participants. These images were warped into a common averaged space, in which the mean and standard deviation templates were both computed. We also developed the SPM analysis programmes to facilitate easy use of the templates. Our templates were validated through the SPM analysis of Alzheimer’s and Parkinson’s patient images. The resultant SPM t-maps accurately depicted the disease-related brain regions with abnormal [18F]-FDG uptake, proving the templates’ effectiveness in brain function impairment analysis.

scholarly journals Approaching Complete Inhibition of P-Glycoprotein at the Human Blood–Brain Barrier: An (R)-[11C]Verapamil PET Study

2015 ◽  
Vol 35 (5) ◽  
pp. 743-746 ◽  
Author(s):  
Martin Bauer ◽  
Rudolf Karch ◽  
Markus Zeitlinger ◽  
Cécile Philippe ◽  
Kerstin Römermann ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Whole Brain ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Positron Emission ◽  
Pet Scans

As P-glycoprotein (Pgp) inhibition at the blood–brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate ( R)-[11C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume ( VT) of ( R)-[11C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.

Basal and glucoprivic-induced changes in extracellular GABA in the ventral hypothalamus of Zucker rats

1996 ◽  
Vol 271 (2) ◽  
pp. R388-R392 ◽  
Author(s):  
S. E. Specter ◽  
B. A. Horwitz ◽  
J. L. Beverly
Keyword(s):  
Food Intake ◽  
Brain Regions ◽  
Gabaergic System ◽  
Aminobutyric Acid ◽  
Zucker Rats ◽  
Gamma Aminobutyric Acid ◽  
Zucker Rat ◽  
Obese Rats ◽  
Before And After ◽  
Induced Changes

The diminished sensitivity of genetically obese (fa/ fa) Zucker rats to the glucoprivic agent 2-deoxy-D-glucose (2-DG) may involve impaired release of the neurotransmitter gamma-aminobutyric acid (GABA) in discrete regions of the hypothalamus. Extracellular GABA concentrations in the medial (MH) and lateral (LH) hypothalamus of lean (Fa/Fa) and age-matched obese (fa/fa) male Zucker rats before and after 2-DG (1.2 mmol/kg i.v.). Basal GABA concentrations were higher (P < 0.05) in the MH of obese vs. lean rats. No differences were noted in LH GABA levels between lean and obese rats or in baseline extracellular GABA levels between brain regions in lean rats. In lean rats, a characteristic bimodal increase in GABA concentrations was apparent in the MH, whereas GABA concentrations decreased in the LH during the 60 min after 2-DG. No changes in GABA concentrations in dialysate from the MH or LH of obese rats were observed after 2-DG. The alterations in basal activity and responsiveness to glucoprivic stimuli by GABAergic system in the MH of obese rats may reflect a defect in central glucostatic control of food intake and, ultimately, in the hypothesized autonomic imbalance in fa/fa Zucker rat.

scholarly journals Medial Orbitofrontal Cortex Is Associated with Fatigue Sensation

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Seiki Tajima ◽  
Shigeyuki Yamamoto ◽  
Masaaki Tanaka ◽  
Yosky Kataoka ◽  
Masao Iwase ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Orbitofrontal Cortex ◽  
Brain Region ◽  
Statistical Parametric Mapping ◽  
Brain Regions ◽  
Mapping Method ◽  
Emission Tomography ◽  
Neural Basis ◽  
Positron Emission ◽  
The Brain

Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performedH2O  15positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmann's area 10/11). Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue.

scholarly journals Kinetic modelling of [11C]PBR28 for 18 kDa translocator protein PET data: A validation study of vascular modelling in the brain using XBD173 and tissue analysis

2017 ◽  
Vol 38 (7) ◽  
pp. 1227-1242 ◽  
Author(s):  
Mattia Veronese ◽  
Tiago Reis Marques ◽  
Peter S Bloomfield ◽  
Gaia Rizzo ◽  
Nisha Singh ◽  
...  
Keyword(s):  
Kinetic Modelling ◽  
Translocator Protein ◽  
Heterogeneous Distribution ◽  
Positron Emission ◽  
Before And After ◽  
Histological Data ◽  
The Central Nervous System ◽  
Specific Tissue ◽  
Pet Scans

The 18 kDa translocator protein (TSPO) is a marker of microglia activation in the central nervous system and represents the main target of radiotracers for the in vivo quantification of neuroinflammation with positron emission tomography (PET). TSPO PET is methodologically challenging given the heterogeneous distribution of TSPO in blood and brain. Our previous studies with the TSPO tracers [11C]PBR28 and [11C]PK11195 demonstrated that a model accounting for TSPO binding to the endothelium improves the quantification of PET data. Here, we performed a validation of the kinetic model with the additional endothelial compartment through a displacement study. Seven subjects with schizophrenia, all high-affinity binders, underwent two [11C]PBR28 PET scans before and after oral administration of 90 mg of the TSPO ligand XBD173. The addition of the endothelial component provided a signal compartmentalization much more consistent with the underlying biology, as only in this model, the blocking study produced the expected reduction in the tracer concentration of the specific tissue compartment, whereas the non-displaceable compartment remained unchanged. In addition, we also studied TSPO expression in vessels using 3D reconstructions of histological data of frontal lobe and cerebellum, demonstrating that TSPO positive vessels account for 30% of the vascular volume in cortical and white matter.

scholarly journals Reference Region Modeling Approaches for Amphetamine Challenge Studies with [11C]FLB 457 and PET

2015 ◽  
Vol 35 (4) ◽  
pp. 623-629 ◽  
Author(s):  
Christine M Sandiego ◽  
Jean-Dominique Gallezot ◽  
Keunpoong Lim ◽  
Jim Ropchan ◽  
Shu-fei Lin ◽  
...  
Keyword(s):  
Arterial Input Function ◽  
Input Function ◽  
Brain Regions ◽  
Reference Region ◽  
Reference Tissue ◽  
Modeling Approaches ◽  
Positron Emission ◽  
Dopaminergic Dysfunction ◽  
Induced Changes ◽  
Tissue Models

Detecting fluctuations in synaptic dopamine levels in extrastriatal brain regions with [11C]FLB 457 and positron emission tomography (PET) is a valuable tool for studying dopaminergic dysfunction in psychiatric disorders. The evaluation of reference region modeling approaches would eliminate the need to obtain arterial input function data. Our goal was to explore the use of reference region models to estimate amphetamine-induced changes in [11C]FLB 457 dopamine D2/D3 binding. Six healthy tobacco smokers were imaged with [11C]FLB 457 at baseline and at 3 hours after amphetamine (0.4  to 0.5 mg/kg, per os) administration. Simplified reference tissue models, SRTM and SRTM2, were evaluated against the 2-tissue compartmental model (2TC) to estimate [11C]FLB 457 binding in extrastriatal regions of interest (ROIs), using the cerebellum as a reference region. No changes in distribution volume were observed in the cerebellum between scan conditions. SRTM and SRTM2 underestimated binding, compared with 2TC, in ROIs by 26% and 9%, respectively, with consistent bias between the baseline and postamphetamine scans. Postamphetamine, [11C]FLB 457 binding significantly decreased across several brain regions as measured with SRTM and SRTM2; no significant change was detected with 2TC. These data support the sensitivity of [11C]FLB 457 for measuring amphetamine-induced dopamine release in extrastriatal regions with SRTM and SRTM2.

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