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 A Simplified in vivo Autoradiographic Strategy for the Determination of Regional Cerebral Blood Flow by Positron Emission Tomography: Theoretical Considerations and Validation Studies in the Rat

1982 ◽  
Vol 2 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Myron D. Ginsberg ◽  
Alan H. Lockwood ◽  
Raul Busto ◽  
Ronald D. Finn ◽  
Cathy M. Butler ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
Animal Studies ◽  
Blood Flow Rate ◽  
Emission Tomography ◽  
Regional Cerebral Blood ◽  
Positron Emission

A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= z). Integrated cranial activity C̄ B is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that [Formula: see text] where each of the terms A x is a readily evaluated function of the blood flow rate constant k, the brain:blood partition coefficient for the tracer, the cranial activity integration limits T1 and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of C̄ B vs. k, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CBF in vivo = CBFclassical X 0.99 − 0.02 (units in ml g−1 min−1; correlation coefficient r = 0.966).

Dopamine D2/3 receptor availability and human cognitive impulsivity: a high-resolution positron emission tomography imaging study with [11C]raclopride

2013 ◽  
Vol 26 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Jong-Hoon Kim ◽  
Young-Don Son ◽  
Hang-Keun Kim ◽  
Sang-Yoon Lee ◽  
Young-Bo Kim ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
High Resolution ◽  
Animal Studies ◽  
Critical Role ◽  
Positron Emission Tomography Imaging ◽  
Imaging Study ◽  
Emission Tomography ◽  
Positron Emission ◽  
Character Inventory ◽  
Behavioural Aspects

ObjectiveHuman impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioural aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. In this study, we investigated the relationship between self-reported impulsiveness and dopamine D2/3 receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride.MethodsTwenty-one participants completed 3-T magnetic resonance imaging and high-resolution PET scans with [11C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D2/3 receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory.ResultsThe analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D2/3 receptor availability in the pre-commissural dorsal caudate. There was a tendency towards positive correlation between non-planning impulsiveness score and D2/3 receptor availability in the post-commissural caudate.ConclusionThese results suggest that cognitive subtrait of impulsivity is associated with D2/3 receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgement of alternative outcomes, and inhibitory control.

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.

Cerebral Metabolism during Propofol Anesthesia in Humans Studied with Positron Emission Tomography 

1995 ◽  
Vol 82 (2) ◽  
pp. 393-403 ◽  
Author(s):  
Michael T. Alkire ◽  
Richard J. Haier ◽  
Steven J. Barker ◽  
Nitin K. Shah ◽  
Joseph C. Wu ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Animal Studies ◽  
Cerebral Metabolism ◽  
Anterior Cingulate ◽  
Emission Tomography ◽  
Whole Brain ◽  
Metabolic Pattern ◽  
Positron Emission ◽  
Cortical Regions

Background Although the effects of propofol on cerebral metabolism have been studied in animals, these effects have yet to be directly examined in humans. Consequently, we used positron emission tomography (PET) to demonstrate in vivo the regional cerebral metabolic changes that occur in humans during propofol anesthesia. Methods Six volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism, and the other assessed metabolism during anesthesia with a propofol infusion titrated to the point of unresponsiveness (mean rate +/- SD = 7.8 +/- 1.5 mg.kg-1.h-1). Scans were obtained using the 18fluorodeoxyglucose technique. Results Awake whole-brain glucose metabolic rates (GMR) averaged 29 +/- 8 mumoles.100 g-1.min-1 (mean +/- SD). Anesthetized whole-brain GMR averaged 13 +/- 4 mumoles.100 g-1.min-1 (paired t test, P < or = 0.007). GMR decreased in all measured areas during anesthesia. However, the decrease in GMR was not uniform. Cortical metabolism was depressed 58%, whereas subcortical metabolism was depressed 48% (P < or = 0.001). Marked differences within cortical regions also occurred. In the medial and subcortical regions, the largest percent decreases occurred in the left anterior cingulate and the inferior colliculus. Conclusion Propofol produced a global metabolic depression on the human central nervous system. The metabolic pattern evident during anesthesia was reproducible and differed from that seen in the awake condition. These findings are consistent with those from previous animal studies and suggest PET may be useful for investigating the mechanisms of anesthesia in humans.

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 Kinetic Compartment Modeling of [11C]-5-Hydroxy-L-Tryptophan for Positron Emission Tomography Assessment of Serotonin Synthesis in Human Brain

2002 ◽  
Vol 22 (11) ◽  
pp. 1352-1366 ◽  
Author(s):  
Gisela E. Hagberg ◽  
Richard Torstenson ◽  
Ina Marteinsdottir ◽  
Mats Fredrikson ◽  
Bengt Långström ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
White Matter ◽  
Tissue Concentration ◽  
Compartment Model ◽  
Anterior Cingulate ◽  
Emission Tomography ◽  
Serotonin Synthesis ◽  
Compartment Modeling ◽  
Arterial Blood ◽  
Positron Emission

The substrate for the second enzymatic step in serotonin synthesis, 5-hydroxy-L-tryptophan, labeled in the β-position ([11C]-HTP), was used for positron emission tomography (PET) measurements in six healthy human participants, examined on two occasions. One- and two-tissue kinetic compartment modeling of time-radioactivity curves was performed, using arterial, metabolite-corrected [11C]-HTP values as input function. The availability of unchanged tracer in arterial blood plasma was ⩽ 80% up to 60 minutes after injection, while [11C]-hydroxyindole acetic acid and [11C]-serotonin accounted for the remaining radioactivity, amounting to ⩽16% and ⩽4%, respectively. Compartment modeling was performed for brain stem, putamen, caudate nucleus, anterior cingulate, white matter, and superior occipital, occipitotemporal, and temporal cortices. The average biologic half-life for plasma-to-tissue equilibrium was 7 to 12 minutes, and the volume of distribution was 0.2 to 0.5 μL·mL−1. In all regions except white matter, the kinetic compartment model that included irreversible [11C]-HTP trapping showed significantly improved model fits with respect to a one-tissue compartment model. The [11C]-HTP trapping rate constant depended on the estimated tissue availability of the serotonin precursor tryptophan, known to reflect serotonin synthesis in healthy individuals, and correlated with serotonin tissue concentration and synthesis rates reported previously in literature. These findings suggest the use of [11C]-HTP PET measurements to investigate serotonin synthesis.

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.

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