scholarly journals Noninvasive Blood-Free Full Quantification of Positron Emission Tomography Radioligand Binding

2014 ◽  
Vol 35 (1) ◽  
pp. 148-156 ◽  
Author(s):  
Francesca Zanderigo ◽  
R Todd Ogden ◽  
Ramin V Parsey
Keyword(s):  
Positron Emission Tomography ◽  
Radioligand Binding ◽  
Partial Agonist ◽  
Brain Regions ◽  
Emission Tomography ◽  
Simultaneous Estimation ◽  
Arterial Line ◽  
Blood Samples ◽  
Arterial Blood ◽  
Positron Emission

Full quantification of a positron emission tomography (PET) radioligand binding to its target is preferred because it requires the fewest assumptions, but generally involves measuring the concentration of free radioligand in the arterial plasma by collecting blood samples from the subject's radial artery during the scan, and performing metabolite analysis. This invasive, costly procedure deters subjects’ participation, and requires specialized staff and equipment. Simultaneous estimation (SIME) can fully quantify binding using only PET data from multiple brain regions and one individual anchor value, which is based on a single arterial blood sample. Drawing this sample can still be challenging in clinical settings, particularly when using simultaneous PET/magnetic resonance scanners. Here we propose a methodology for full quantification of binding that does not require any blood samples. The methodology substitutes the SIME blood-based anchor with a value predicted using multiple linear regression of noninvasive, easy-to-collect variables related to the radioligand blood concentration, and individual metabolism, such as injected dose, body mass index, or body surface area. As a study case, we show here the methodology in comparison to analysis with full arterial-line blood sampling in a cohort of 23 available scans with [11C]CUMI-101, a partial agonist of the serotonin 5-HT1A receptors.

scholarly journals Global Cerebral Blood Flow Decreases during Pain

1998 ◽  
Vol 18 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Robert C. Coghill ◽  
Christine N. Sang ◽  
Karen Faith Berman ◽  
Gary J. Bennett ◽  
Michael J. Iadarola
Keyword(s):  
Positron Emission Tomography ◽  
Heart Rate ◽  
Brain Regions ◽  
Intradermal Injection ◽  
Emission Tomography ◽  
Intravenous Bolus ◽  
Arterial Blood Sampling ◽  
Arterial Blood ◽  
Positron Emission ◽  
Global Cerebral Blood Flow

Positron emission tomography studies have identified a common set of brain regions activated by pain. No studies, however, have quantitatively examined pain-induced CBF changes. To better characterize CBF during pain, 14 subjects received positron emission tomography scans during rest, during capsaicin-evoked pain (250 μg, intradermal injection), and during innocuous vibration. Using the H215O intravenous bolus method with arterial blood sampling, global CBF changes were assessed quantitatively. Painful stimulation produced a 22.8% decrease in global CBF from resting levels ( P < 0.0005). This decrease was not accounted for by arterial PCO2 or heart rate changes. Although the exact mechanism remains to be determined, this pain-induced global decrease represents a previously unidentified response of CBF.

scholarly journals Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España
Keyword(s):  
Positron Emission Tomography ◽  
Blood Sample ◽  
Pet Imaging ◽  
Spectroscopic Analysis ◽  
Gamma Spectroscopy ◽  
Emission Tomography ◽  
Blood Samples ◽  
Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

Validation and optimisation of an automatic blood sampler for preclinical positron emission tomography research in domestic pigs

2021 ◽  
pp. 002367722110490
Author(s):  
Sofia Vestergaard Nielsen ◽  
Mie Ringgaard Dollerup ◽  
Simone Larsen Bærentzen ◽  
Anne M Landau ◽  
Ole Lajord Munk ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Animal Studies ◽  
Time Course ◽  
Activity Concentration ◽  
Blood Sampling ◽  
Emission Tomography ◽  
Domestic Pigs ◽  
Arterial Blood ◽  
Positron Emission

In preclinical positron emission tomography animal studies, continuous blood sampling is used to measure the time course of the activity concentration in arterial blood. However, pigs have hypercoagulable blood that tends to clot inside plastic tubes. We tested several tube materials and lengths and the use of three-way connectors. We validated set-ups for automated blood sampling with and without blood recirculation that could run for 90 minutes without problematic clots and without any evidence of emboli formation during necropsy.

scholarly journals Quantification of PET infusion studies without true equilibrium: A tissue clearance correction

2019 ◽  
Vol 40 (4) ◽  
pp. 860-874
Author(s):  
Ansel T Hillmer ◽  
Richard E Carson
Keyword(s):  
Positron Emission Tomography ◽  
Data Analysis ◽  
Brain Regions ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Constant Infusion ◽  
Scanning Time ◽  
Positron Emission ◽  
Study Population ◽  
True Equilibrium

In some positron emission tomography (PET) studies, a reversibly binding radioligand is administered as a constant infusion to establish true equilibrium for quantification. This approach reduces scanning time and simplifies data analysis, but assumes similar behavior of the radioligand in plasma across the study population to establish true equilibrium in all subjects. Bias in outcome measurements can result if this assumption is not met. This work developed and validated a correction that reduces bias in total distribution volume ( VT) estimates when true equilibrium is not present. This correction, termed tissue clearance correction (TCC), took the form [Formula: see text], where β is the radioligand clearance rate in tissue, γ is a radiotracer-specific constant, and VT(A) is the apparent VT. Simulations characterized the robustness of TCC across imperfect values of γ and β and demonstrated reduction to false positive rates. This approach was validated with human infusion data for three radiotracers: [18F]FPEB, (−)-[18F]flubatine, and [11C]UCB-J. TCC reduced bias in VT estimates for all radiotracers and significantly reduced intersubject variance in VT for [18F]FPEB data in some brain regions. Thus, TCC improves quantification of data acquired from PET infusion studies.

29 POSITRON EMISSION TOMOGRAPHY IMAGING OF BRAIN METABOLISM AND DOPAMINERGIC NEURON DESTRUCTION IN PARKINSON'S DISEASE MODEL PIG

2017 ◽  
Vol 29 (1) ◽  
pp. 122
Author(s):  
H. J. Oh ◽  
J. Moon ◽  
G. A. Kim ◽  
S. Lee ◽  
S. H. Paek ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Dopaminergic Neuron ◽  
Brain Metabolism ◽  
Brain Research ◽  
Brain Regions ◽  
Emission Tomography ◽  
Positron Emission ◽  
Significant Difference ◽  
And Control ◽  
The Brain

Due to similarities between human and porcine, pigs have been proposed as an excellent experimental animal for human medical research. Especially in paediatric brain research, piglets share similarities with human infants in the extent of peak brain growth at the time of birth and the growth pattern of brain. Thus, these findings have supported the wider use of pigs rather than rodents in neuroscience research. Previously, we reported the production of porcine model of Parkinson's disease (PD) by nuclear transfer using donor cell that had been stably infected with lentivirus containing the human α-synuclein gene. The purpose of this study was to determine the alternation of brain metabolism and dopaminergic neuron destruction using noninvasive method in a 2-yr-old PD model and a control pig. The positron emission tomography (PET) scan was done using Biograph TruePoint40 with a TrueV (Siemens, Munich, Germany). The [18F]N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) was administrated via the ear vein. Static images of the brain for 15 min were acquired from 2 h after injection. The 18F-fluorodeoxy-D-glucose PET (18F-FDG PET) images of the brain were obtained for 15 min at 45 min post-injection. Computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed at the same location of the brain. In both MRI and CT images, there was no difference in brain regions between PD model and control pigs. However, administration of [18F]FP-CIT was markedly decreased in the bilateral putamen of the PD model pig compared with the control pigs. Moreover, [18F]FP-CIT administration was asymmetrical in the PD model pig but it was symmetrical in control pigs. Regional brain metabolism was also assessed and there was no significant difference in cortical metabolism of PD model and control pigs. We demonstrated that PET imaging could provide a foundation for translational Parkinson neuroimaging in transgenic pigs. In the present study, a 2-yr-old PD model pig showed dopaminergic neuron destruction in brain regions. Therefore, PD model pig expressing human α-synuclein gene would be an efficient model for human PD patients. This study was supported by Korea IPET (#311011–05–5-SB010), Research Institute for Veterinary Science, TS Corporation and the BK21 plus program.

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 Comparison of cerebral blood flow measurement with [15O]-water positron emission tomography and arterial spin labeling magnetic resonance imaging: A systematic review

2016 ◽  
Vol 36 (5) ◽  
pp. 842-861 ◽  
Author(s):  
Audrey P Fan ◽  
Hesamoddin Jahanian ◽  
Samantha J Holdsworth ◽  
Greg Zaharchuk
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Arterial Spin Labeling ◽  
Brain Perfusion ◽  
Spin Labeling ◽  
Emission Tomography ◽  
Flow Measurements ◽  
Arterial Blood ◽  
Positron Emission

Noninvasive imaging of cerebral blood flow provides critical information to understand normal brain physiology as well as to identify and manage patients with neurological disorders. To date, the reference standard for cerebral blood flow measurements is considered to be positron emission tomography using injection of the [15O]-water radiotracer. Although [15O]-water has been used to study brain perfusion under normal and pathological conditions, it is not widely used in clinical settings due to the need for an on-site cyclotron, the invasive nature of arterial blood sampling, and experimental complexity. As an alternative, arterial spin labeling is a promising magnetic resonance imaging technique that magnetically labels arterial blood as it flows into the brain to map cerebral blood flow. As arterial spin labeling becomes more widely adopted in research and clinical settings, efforts have sought to standardize the method and validate its cerebral blood flow values against positron emission tomography-based cerebral blood flow measurements. The purpose of this work is to critically review studies that performed both [15O]-water positron emission tomography and arterial spin labeling to measure brain perfusion, with the aim of better understanding the accuracy and reproducibility of arterial spin labeling relative to the positron emission tomography reference standard.

scholarly journals Evaluation of [13N]ammonia positron emission tomography as a potential method for quantifying glutamine synthetase activity in the human brain.

2020 ◽  
Author(s):  
Alice Egerton ◽  
Joel Dunn ◽  
Nisha Singh ◽  
Zilin Yu ◽  
Jim O'Doherty ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Glutamine Synthetase ◽  
Human Brain ◽  
Kinetic Modelling ◽  
Emission Tomography ◽  
Synthetase Activity ◽  
Glutamine Synthetase Activity ◽  
Kinetic Rate Constant ◽  
Arterial Blood ◽  
Positron Emission

Abstract Purpose: The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [13N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans.Methods: In this test-retest study, eight healthy volunteers each received two dynamic [13N]ammonia PET scans on the morning and afternoon of the same day. Each [13N]ammonia scan was preceded by a [15O]water PET scan to account for effects of cerebral blood flow (CBF).Results: Concentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constant k3 (related to GS activity) from K1 (related to [13N]ammonia brain uptake), and indicated a non-negligible back-flux of [13N] to blood (k2). Model selection favoured a reversible one-tissue compartmental model, and [13N]ammonia K1 correlated reliably (r2 = 0.72 - 0.92) with [15O]water CBF.Conclusion: The [13N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.

scholarly journals Network Diffusion Modeling Explains Longitudinal Tau PET Data

2020 ◽  
Vol 14 ◽  
Author(s):  
Amelie Schäfer ◽  
Elizabeth C. Mormino ◽  
Ellen Kuhl
Keyword(s):  
Positron Emission Tomography ◽  
Clinical Symptoms ◽  
Dynamic Network ◽  
Network Models ◽  
Brain Regions ◽  
Brain Network ◽  
Emission Tomography ◽  
Model Parameters ◽  
Positron Emission ◽  
Network Diffusion

Alzheimer's disease is associated with the cerebral accumulation of neurofibrillary tangles of hyperphosphorylated tau protein. The progressive occurrence of tau aggregates in different brain regions is closely related to neurodegeneration and cognitive impairment. However, our current understanding of tau propagation relies almost exclusively on postmortem histopathology, and the precise propagation dynamics of misfolded tau in the living brain remain poorly understood. Here we combine longitudinal positron emission tomography and dynamic network modeling to test the hypothesis that misfolded tau propagates preferably along neuronal connections. We follow 46 subjects for three or four annual positron emission tomography scans and compare their pathological tau profiles against brain network models of intracellular and extracellular spreading. For each subject, we identify a personalized set of model parameters that characterizes the individual progression of pathological tau. Across all subjects, the mean protein production rate was 0.21 ± 0.15 and the intracellular diffusion coefficient was 0.34 ± 0.43. Our network diffusion model can serve as a tool to detect non-clinical symptoms at an earlier stage and make informed predictions about the timeline of neurodegeneration on an individual personalized basis.

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