scholarly journals A Two-Compartment Mathematical Model of Neuroglial Metabolism Using [1-11C] Acetate

2011 ◽  
Vol 32 (3) ◽  
pp. 548-559 ◽  
Author(s):  
Bernard Lanz ◽  
Kai Uffmann ◽  
Matthias T Wyss ◽  
Bruno Weber ◽  
Alfred Buck ◽  
...  
Keyword(s):  
Brain Metabolism ◽  
Arterial Input Function ◽  
Tca Cycle ◽  
Compartment Model ◽  
Metabolic Model ◽  
Input Function ◽  
Resonance Spectroscopy ◽  
Uptake Curve ◽  
Metabolic Fluxes ◽  
Good Agreement

The purpose of this study was to develop a two-compartment metabolic model of brain metabolism to assess oxidative metabolism from [1-11C] acetate radiotracer experiments, using an approach previously applied in 13C magnetic resonance spectroscopy (MRS), and compared with an one-tissue compartment model previously used in brain [1-11C] acetate studies. Compared with 13C MRS studies, 11C radiotracer measurements provide a single uptake curve representing the sum of all labeled metabolites, without chemical differentiation, but with higher temporal resolution. The reliability of the adjusted metabolic fluxes was analyzed with Monte-Carlo simulations using synthetic 11C uptake curves, based on a typical arterial input function and previously published values of the neuroglial fluxes Vtcag, Vx, Vnt, and Vtcan measured in dynamic 13C MRS experiments. Assuming Vxg=10 × Vtcag and Vxn= Vtcan, it was possible to assess the composite glial tricarboxylic acid (TCA) cycle flux Vgtg ( Vgtg= Vxg × Vtcag/( Vxg+ Vtcag)) and the neurotransmission flux Vnt from 11C tissue-activity curves obtained within 30 minutes in the rat cortex with a beta-probe after a bolus infusion of [1-11C] acetate ( n=9), resulting in Vgtg=0.136±0.042 and Vnt=0.170±0.103 μmol/g per minute (mean±s.d. of the group), in good agreement with 13C MRS measurements.

scholarly journals Assessment of Metabolic Fluxes in the Mouse Brain in Vivo Using 1H-[13C] NMR Spectroscopy at 14.1 Tesla

2015 ◽  
Vol 35 (5) ◽  
pp. 759-765 ◽  
Author(s):  
Lijing Xin ◽  
Bernard Lanz ◽  
gxia Lei ◽  
Rolf Gruetter
Keyword(s):  
Mouse Models ◽  
Mouse Brain ◽  
Conversion Rate ◽  
Tca Cycle ◽  
Compartment Model ◽  
13C Nmr Spectroscopy ◽  
Resonance Spectroscopy ◽  
Metabolic Fluxes ◽  
Short Echo Time

13C magnetic resonance spectroscopy (MRS) combined with the administration of 13C labeled substrates uniquely allows to measure metabolic fluxes in vivo in the brain of humans and rats. The extension to mouse models may provide exclusive prospect for the investigation of models of human diseases. In the present study, the short-echo-time (TE) full-sensitivity 1H-[13C] MRS sequence combined with high magnetic field (14.1 T) and infusion of [U-13C6] glucose was used to enhance the experimental sensitivity in vivo in the mouse brain and the 13C turnover curves of glutamate C4, glutamine C4, glutamate+glutamine C3, aspartate C2, lactate C3, alanine C3, γ-aminobutyric acid C2, C3 and C4 were obtained. A one-compartment model was used to fit 13C turnover curves and resulted in values of metabolic fluxes including the tricarboxylic acid (TCA) cycle flux VTCA (1.05 ± 0.04 μmol/g per minute), the exchange flux between 2-oxoglutarate and glutamate Vx (0.48 ± 0.02 μmol/g per minute), the glutamate-glutamine exchange rate Vgln (0.20 ± 0.02 μmol/g per minute), the pyruvate dilution factor Kdil (0.82 ± 0.01), and the ratio for the lactate conversion rate and the alanine conversion rate VLac/ VAla (10 ± 2). This study opens the prospect of studying transgenic mouse models of brain pathologies.

scholarly journals Quantitative Myocardial Perfusion with 2D and 3D Sequences Alternating Every Heartbeat

2021 ◽  
Author(s):  
Qi Huang ◽  
Ye Tian ◽  
Jason Mendes ◽  
Ravi Ranjan ◽  
Ganesh Adluru ◽  
...  
Keyword(s):  
Myocardial Perfusion ◽  
Arterial Input Function ◽  
Compartment Model ◽  
Input Function ◽  
Saturation Recovery ◽  
Quantitative Perfusion ◽  
Stress Studies ◽  
Two Compartment Model ◽  
Quantitative Myocardial Perfusion ◽  
3D Sequences

Abstract PurposeTo evaluate a myocardial perfusion acquisition that alternates 2D simultaneous multi-slice (SMS) and 3D stack-of-stars (SoS) acquisitions each heartbeat. MethodsA hybrid saturation recovery radial 2D SMS and a saturation recovery 3D SoS sequence were created for the quantification of myocardial blood flow (MBF). Initial studies were done to study the effects of using only every other beat for the 2D SMS in two subjects, and for the 3D SoS in two subjects. Alternating heartbeat 2D SMS and 3D SoS were then performed in ten dog studies at rest, four dog studies at adenosine stress, and two human resting studies. 2D SMS acquisition acquired three slices and 3D SoS acquired six slices. An arterial input function (AIF) for 2D SMS was obtained using the first 24 rays. For 3D, the AIF was obtained in a 2D slice prior to each 3D SoS readout. Quantitative MBF analysis was performed for 2D SMS and 3D SoS separately, using a two-compartment model. ResultsAcquiring every-other-beat data resulted in 5-20% perfusion changes at rest for both 2D SMS and 3D SoS methods. For alternating acquisitions, 2D SMS and 3D SoS quantitative perfusion values were comparable for both the twelve rest studies (2D SMS: 0.68±0.15 vs 3D: 0.69±0.15 ml/g/min, p=0.85) and the four stress studies (2D SMS: 1.28±0.22 vs 3D: 1.30±0.24 ml/g/min, p=0.66).ConclusionEvery-other-beat acquisition changed estimated perfusion values relatively little for both sequences. 2D SMS and 3D SoS gave similar quantitative perfusion estimates when used in an alternating every-other-heartbeat acquisition. Such an approach allows consideration of more diverse perfusion acquisitions that could have complementary features, although testing in a cardiac disease population is needed.

scholarly journals Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET

2019 ◽  
Vol 40 (11) ◽  
pp. 2254-2264 ◽  
Author(s):  
Sophie E Holmes ◽  
Jean-Dominique Gallezot ◽  
Margaret T Davis ◽  
Nicole DellaGioia ◽  
David Matuskey ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Arterial Input Function ◽  
Compartment Model ◽  
Input Function ◽  
Treatment Target ◽  
Ketamine Infusion ◽  
Metabotropic Glutamate ◽  
Glutamate Transmission ◽  
Promising Treatment ◽  
Drug Challenge

The metabotropic glutamate receptor 5 (mGluR5) is a promising treatment target for psychiatric disorders due to its modulatory effects on glutamate transmission. Using [11C]ABP688, we previously showed that the rapidly acting antidepressant ketamine decreases mGluR5 availability. The mGluR5 radioligand [18F]FPEB offers key advantages over [11C]ABP688; however, its suitability for drug challenge studies is unknown. We evaluated whether [18F]FPEB can be used to capture ketamine-induced effects on mGluR5. Seven healthy subjects participated in three [18F]FPEB scans: a baseline, a same-day post-ketamine, and a 24-h post-ketamine scan. The outcome measure was VT/ fP, obtained using a two-tissue compartment model and a metabolite-corrected arterial input function. Dissociative symptoms, heart rate and blood pressure increased following ketamine infusion. [18F]FPEB VT/ fP decreased by 9% across the cortex after ketamine infusion, with minimal difference between baseline and 24-h scans. Compared to our previous work using [11C]ABP688, the magnitude of the ketamine-induced change in mGluR5 was smaller using [18F]FPEB; however, effect sizes were similar for the same-day post-ketamine vs. baseline scan (Cohen’s d = 0.75 for [18F]FPEB and 0.88 for [11C]ABP688). [18F]FPEB is therefore able to capture some of the effects of ketamine on mGluR5, but [11C]ABP688 appears to be more suitable in drug challenge paradigms designed to probe glutamate transmission.

scholarly journals Region- and voxel-based quantification in human brain of [18F]LSN3316612, a radioligand for O-GlcNAcase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae-Hoon Lee ◽  
Mattia Veronese ◽  
Jeih-San Liow ◽  
Cheryl L. Morse ◽  
Jose A. Montero Santamaria ◽  
...  
Keyword(s):  
Human Brain ◽  
Arterial Input Function ◽  
Impulse Response Function ◽  
Standardized Uptake Value ◽  
Compartment Model ◽  
Input Function ◽  
Strongly Correlated ◽  
Parametric Images ◽  
Logan Plot ◽  
Positron Emission

Abstract Background Previous studies found that the positron emission tomography (PET) radioligand [18F]LSN3316612 accurately quantified O-GlcNAcase in human brain using a two-tissue compartment model (2TCM). This study sought to assess kinetic model(s) as an alternative to 2TCM for quantifying [18F]LSN3316612 binding, particularly in order to generate good-quality parametric images. Methods The current study reanalyzed data from a previous study of 10 healthy volunteers who underwent both test and retest PET scans with [18F]LSN3316612. Kinetic analysis was performed at the region level with 2TCM using 120-min PET data and arterial input function, which was considered as the gold standard. Quantification was then obtained at both the region and voxel levels using Logan plot, Ichise's multilinear analysis-1 (MA1), standard spectral analysis (SA), and impulse response function at 120 min (IRF120). To avoid arterial sampling, a noninvasive relative quantification (standardized uptake value ratio (SUVR)) was also tested using the corpus callosum as a pseudo-reference region. Venous samples were also assessed to see whether they could substitute for arterial ones. Results Logan and MA1 generated parametric images of good visual quality and their total distribution volume (VT) values at both the region and voxel levels were strongly correlated with 2TCM-derived VT (r = 0.96–0.99) and showed little bias (up to − 8%). SA was more weakly correlated to 2TCM-derived VT (r = 0.93–0.98) and was more biased (~ 16%). IRF120 showed a strong correlation with 2TCM-derived VT (r = 0.96) but generated noisier parametric images. All techniques were comparable to 2TCM in terms of test–retest variability and reliability except IRF120, which gave significantly worse results. Noninvasive SUVR values were not correlated with 2TCM-derived VT, and arteriovenous equilibrium was never reached. Conclusions Compared to SA and IRF, Logan and MA1 are more suitable alternatives to 2TCM for quantifying [18F]LSN3316612 and generating good-quality parametric images.

scholarly journals Quantification of human brain PDE4 occupancy by GSK356278: A [11C](R)-rolipram PET study

2017 ◽  
Vol 38 (11) ◽  
pp. 2033-2040 ◽  
Author(s):  
Jasper van der Aart ◽  
Cristian Salinas ◽  
Rahul Dimber ◽  
Sabina Pampols-Maso ◽  
Ashley A Weekes ◽  
...  
Keyword(s):  
Human Brain ◽  
Arterial Input Function ◽  
Compartment Model ◽  
Input Function ◽  
Post Dose ◽  
Emission Data ◽  
Pet Tracer ◽  
Positron Emission ◽  
Tolerability Data

We characterized the relationship between the plasma concentration of the phospodiesterase (PDE)-4 inhibitor GSK356278 and occupancy of the PDE4 enzyme in the brain of healthy volunteers, using the positron emission tomography (PET) tracer [11C](R)-rolipram. To this end, PET scans were acquired in eight male volunteers before and at 3 and 8 h after a single 14 mg oral dose of GSK356278. A metabolite-corrected arterial input function was used in conjunction with the dynamic PET emission data to estimate volumes of distribution (VT) from a two-tissue compartment model. The administration of GSK356278 reduced [11C](R)-rolipram whole brain VT by 17% at 3 h post-dose (p = 0.01) and by 4% at 8 h post-dose. The mean plasma Cmax was 42.3 ng/ml, leading to a PDE4 occupancy of 48% at Tmax. The in vivo affinity of GSK356278 was estimated as EC50 = 46 ± 3.6 ng/ml. We present the first report of a direct estimation of PDE4 blockade in the living human brain. In vivo affinity of GSK356278 for the PDE4, estimated in this early phase study, was combined with GSK356278 safety and tolerability data to decide on a therapeutic dose for future clinical development.

scholarly journals Kinetic Modeling without Accounting for the Vascular Component Impairs the Quantification of [11C]PBR28 Brain PET Data

2014 ◽  
Vol 34 (6) ◽  
pp. 1060-1069 ◽  
Author(s):  
Gaia Rizzo ◽  
Mattia Veronese ◽  
Matteo Tonietto ◽  
Paolo Zanotti-Fregonara ◽  
Federico E Turkheimer ◽  
...  
Keyword(s):  
Arterial Input Function ◽  
Compartment Model ◽  
Input Function ◽  
Translocator Protein ◽  
Brain Vessels ◽  
Data Set ◽  
Potential Marker ◽  
Positron Emission ◽  
Vascular Component ◽  
The Impact

The positron emission tomography radioligand [11C]PBR28 targets translocator protein (18 kDa) (TSPO) and is a potential marker of neuroinflammation. [11C]PBR28 binding is commonly quantified using a two-tissue compartment model and an arterial input function. Previous studies with [11C]HRJ-PK11195 demonstrated a slow irreversible binding component to the TSPO proteins localized in the endothelium of brain vessels, such as venous sinuses and arteries. However, the impact of this component on the quantification of [11C]PBR28 data has never been investigated. In this work we propose a novel kinetic model for [11C]PBR28. This model hypothesizes the existence of an additional irreversible component from the blood to the endothelium. The model was tested on a data set of 19 healthy subjects. A simulation was also performed to quantify the error generated by the standard two-tissue compartmental model when the presence of the irreversible component is not taken into account. Our results show that when the vascular component is included in the model the estimates that include the vascular component (2TCM-1K) are more than three-fold smaller, have a higher time stability and are better correlated to brain mRNA TSPO expression than those that do not include the model (2TCM).

scholarly journals Laplace Transform Method for 11C-PIB Two-Tissue Reversible Compartment Model with Image-Derived Arterial Input Function

2017 ◽  
Author(s):  
Eliete Biasotto Hauser ◽  
Gianina Teribele Venturin ◽  
Evandro Manica ◽  
Samuel Greggio ◽  
Eduardo Zimmer ◽  
...  
Keyword(s):  
Laplace Transform ◽  
Arterial Input Function ◽  
Compartment Model ◽  
Input Function ◽  
Laplace Transform Method ◽  
Transform Method

scholarly journals An Untargeted Metabolomics Investigation of Milk from Dairy Cows with Clinical Mastitis by 1H-NMR

Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1707
Author(s):  
Chenglin Zhu ◽  
Kaiwei Tang ◽  
Xuan Lu ◽  
Junni Tang ◽  
Luca Laghi
Keyword(s):  
Dairy Cows ◽  
1H Nmr ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Quantitative Information ◽  
Clinical Mastitis ◽  
Economic Losses ◽  
Resonance Spectroscopy ◽  
Mastitic Milk ◽  
Chemical Groups

Mastitis is one of the diseases with the highest incidence in dairy cows, causing huge economic losses to the dairy industry all over the world. The aim of the study was to characterize mastitic milk metabolome through untargeted nuclear magnetic resonance spectroscopy (1H-NMR). Taking advantage of the high reproducibility of 1H-NMR, we had the opportunity to provide quantitative information for all the metabolites identified. Fifty-four molecules were characterized, sorted mainly into the chemical groups, namely amino acids, peptides and analogues, carbohydrates and derivates, organic acids and derivates, nucleosides, nucleotides and analogues. Combined with serum metabolomic investigations, several pathways were addressed to explain the mechanisms of milk metabolome variation affected by clinical mastitis, such as tricarboxylic acid cycle (TCA cycle) and phenylalanine, tyrosine and tryptophan biosynthesis. These results provide a further understanding of milk metabolome altered by clinical mastitis, which can be used as a reference for the further milk metabolome investigations.

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