scholarly journals Noninvasive Estimation of Normalized Distribution Volume: Application to the Muscarinic-2 Ligand [18F]FP-TZTP

2007 ◽  
Vol 28 (2) ◽  
pp. 420-430 ◽  
Author(s):  
Masanori Ichise ◽  
Robert M Cohen ◽  
Richard E Carson
Keyword(s):  
Statistical Significance ◽  
Free Fraction ◽  
Cholinergic Receptor ◽  
Distribution Volume ◽  
Reference Region ◽  
Reference Tissue ◽  
Apoe Ε4 ◽  
Arterial Blood ◽  
Noninvasive Estimation ◽  
Input Region

Reference tissue methods to estimate neuroreceptor binding are not applicable to [18F]FP-TZTP (a muscarinic-2 cholinergic receptor ligand), because there is no suitable receptor-free reference region. We evaluated a new method to estimate, without using arterial data or a receptor-free reference region, a receptor parameter called the normalized distribution volume, V*T, using a region containing receptors as the input tissue. V*T is defined as VT /K′1 (distribution volume ( VT) normalized by K′1 of the input region). We used a two-parameter multilinear reference tissue model (MRTM2) to generate parametric images of V*T and R1 ( R1 = K1/ K′1) from [18F]FP-TZTP PET data of healthy aged subjects (10 with apolipoprotein E-ε4 alleles (APOE-ε4(+)) and nine without (APOE-ε4(–)). VT and VT were normalized by plasma-free fraction, fP. By one-tissue kinetic analysis (1TKA) with metabolite-corrected plasma data, VT was previously reported as higher in the APOE-ε4(+) group. The noise magnitude of MRTM2 V*T and R1 images were nearly identical to those of 1TKA VT and K1 images. K′1 or fP was not different between the two groups. V*T (mins) (1,659 ± 497) and VT (mL/cm3) (701 ± 99) in APOE-ε4(+) were higher by 38 and 22% than those (1,209 ± 233 and 577 ± 112) in APOE-ε4(–), respectively. The statistical significance for V*T (0.041) was lower than that for VT (0.025), due to the higher intersubject variability of V*T (25%) than that of VT (17%). We conclude that MRTM2 V*T allows detection of group differences in receptor binding without arterial blood or a receptor-free reference region.

scholarly journals In Vivo Quantification of Cerebral Muscarinic Receptors in Normal Human Aging Using Positron Emission Tomography and [11C]Tropanyl Benzilate

1996 ◽  
Vol 16 (2) ◽  
pp. 303-310 ◽  
Author(s):  
Kien S. Lee ◽  
Kirk A. Frey ◽  
Robert A. Koeppe ◽  
Alfred Buck ◽  
G. Keith Mulholland ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Cholinergic Receptor ◽  
Elderly Subjects ◽  
Arterial Blood ◽  
Cholinergic Dysfunction ◽  
Positron Emission ◽  
Radiotracer Injection ◽  
Major Loss ◽  
Normal Human

Regional cerebral muscarinic cholinergic receptor binding was quantified in normal young and elderly subjects employing the muscarinic antagonist radioligand [11C]tropanyl benzilate (TRB). Binding was determined by kinetic analyses of positron emission tomographic (PET) determinations of cerebral activity in conjunction with radial arterial blood sampling following intravenous radiotracer injection. A significant, but minor (8%), loss of frontal cortical receptors relative to whole brain average receptor density was found with advancing age. Parametric estimates of binding suggest small reductions in cerebral cortex binding as well as increases in brain stem and cerebellar binding underlying the observed pattern difference. However, these latter changes did not achieve statistical significance. We conclude that cerebral muscarinic receptor availability, as depicted by antagonist binding, does not undergo a major decline during normal aging of the adult human brain. The cerebral cortical cholinergic dysfunction in elderly subjects, suggested by prior clinical evidence, is not attributable to major loss of total muscarinic cholinoceptive capacity.

scholarly journals In vivo and in vitro Validation of Reference Tissue Models for the mGluR5 Ligand [11C]ABP688

2010 ◽  
Vol 30 (8) ◽  
pp. 1538-1549 ◽  
Author(s):  
David Elmenhorst ◽  
Luciano Minuzzi ◽  
Antonio Aliaga ◽  
Jared Rowley ◽  
Gassan Massarweh ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Primary Objective ◽  
Binding Potential ◽  
Reference Region ◽  
Reference Tissue ◽  
Caudate Putamen ◽  
Average Decrease ◽  
Arterial Blood

The primary objective of this study was to verify the suitability of reference tissue-based quantification methods of the metabotropic glutamate receptor type 5 (mGluR5) with [11C]ABP688. This study presents in vivo (Positron Emission Tomography (PET)) and in vitro (autoradiography) measurements of mGluR5 densities in the same rats and evaluates both noninvasive and blood-dependent pharmacokinetic models for the quantification of [11C]ABP688 binding. Eleven rats underwent [11C]ABP688 PET scans. In five animals, baseline scans were compared with blockade experiments with the antagonist 1,2-methyl-6-(phenylethynyl)-pyridine (MPEP), and arterial blood samples were drawn and corrected for metabolites. Afterward, saturation-binding autoradiography was performed. Blocking with MPEP resulted in an average decrease of the total distribution volume ( VT) between 43% and 58% (thalamus and caudate-putamen, respectively) but had no significant effect on cerebellar VT (mean reduction: −0.01%). Comparing binding potential ( BPND) based on the VT with noninvasively determined BPND revealed an average negative bias of 0.7% in the caudate-putamen and an average positive bias of 3.1% in the low-binding regions. Scan duration of 50 minutes is required. The cerebellum is a suitable reference region for the quantification of mGluR5 availability as measured with [11C]ABP688 PET in rats. Blood-based and reference region-based PET quantification shows a significant linear relationship to autoradiographic determinations.

The effect of mask use on maternal oxygen saturation in term pregnancies during the COVID-19 process

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Erzat Toprak ◽  
Ayça Nazlı Bulut
Keyword(s):  
Oxygen Saturation ◽  
Pregnant Women ◽  
Stress Test ◽  
Statistical Significance ◽  
Categorical Variables ◽  
Fisher Exact Test ◽  
Coin Toss ◽  
Arterial Blood ◽  
Surgical Masks ◽  
Before And After

AbstractObjectivesOur aim was to evaluate the effect of standard surgical and N-95 respiratory mask use on maternal oxygen saturation, vital signs and result on non-stress tests in term pregnancies.MethodsIt is a prospective observational study. The study included healthy, not in labor, singleton pregnant women of 370/7–410/7 weeks who were applied to our hospital for routine obstetric control examination between March 1, 2020, and August 31, 2020. Patients were randomised by coin toss method. Oxygen saturation, systolic, and diastolic arterial blood pressure, pulse, respiratory rate, and temperature of pregnant women using surgical masks and respiratory masks were measured before and after the non-stress test. The tolerance of the masks was also evaluated. Student’s t-test was used for variables showing parametric distribution and the Mann Whitney U-test was used for non-parametric tests. The categorical variables between the groups was analyzed by using the Chi square test or Fisher Exact test. The statistical significance level was taken as p<0.05 in all tests.ResultsA total of 297 pregnant women using masks were included in the study. The effect of mask type on oxygen saturation before and after the non-stress test was found to be significant (97.1±1.8 corresponds to 95.3±2.6 for the surgical mask, p=0.0001; 97.8±1.7 corresponds to 93.7±2.0 for the respiratory mask, p=0.0001). Mask tolerance of patients using respiratory masks was significantly higher than those using surgical masks (mean 8, 1–10, p=0.0001).ConclusionsSurgical mask and respiratory mask usage decreased significantly in oxygen saturation in term pregnancies.

scholarly journals Impact of APOE ε4 genotype on initial cognitive symptoms differs for Alzheimer’s and Lewy body neuropathology

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jagan A. Pillai ◽  
James Bena ◽  
Aaron Bonner-Jackson ◽  
James B. Leverenz
Keyword(s):  
Lewy Body ◽  
Statistical Significance ◽  
Carrier Status ◽  
Initial Symptom ◽  
Cognitive Symptoms ◽  
Clinical Dementia Rating ◽  
Apoe Ε4 ◽  
Initial Symptoms ◽  
Adjusted Model ◽  
The Impact

Abstract Background APOE ε4 carrier status is known to increase odds of amnestic presentations with Alzheimer’s pathology. It is unknown how APOE ε4 carrier status impacts odds of specific initial cognitive symptoms in the presence of Lewy body pathology. Here we evaluate the impact of APOE ε4 genotype on initial cognitive symptoms among those with Alzheimer’s disease pathology (ADP) and Lewy-related pathology (LRP). Methods A retrospective cohort study of 2288 participants with neuropathology confirmed ADP or LRP in the National Alzheimer’s Coordinating Center database, who had initial cognitive symptoms documented and had a Clinical Dementia Rating-Global (CDR-G) score ≤ 1 (cognitively normal, MCI, or early dementia). Unadjusted and adjusted logistic regression models taking into account age at evaluation, sex, and education examined the relationship between APOE ε4 genotype and initial symptoms (memory, executive, language visuospatial) among ADP with LRP and ADP-LRP groups. Results One thousand three hundred three participants met criteria for ADP alone, 90 for LRP alone, and 895 for co-existing ADP and LRP (ADP-LRP). Younger age increased odds of non-amnestic symptoms across all three groups. In the adjusted model among ADP, APOE ε4 carriers had higher odds of amnestic initial symptoms 1.5 [95% CI, 1.7–2.14, p = 0.003] and lower odds of initial language symptoms 0.67 [95% CI, 0.47–0.96, p = 0.03] than non-carriers. The odds for these two symptoms were not different between ADP and mixed ADP-LRP groups. Female sex and higher education increased odds of initial language symptoms in the ADP group in the adjusted model. In the unadjusted model, APOE ε4 carriers with LRP had a higher odds of visuospatial initial symptoms 21.96 [95% CI, 4.02–110.62, p < 0.0001], while no difference was noted for initial executive/attention symptoms. Among LRP, the odds of APOE ε4 on amnestic symptom was not significant; however, the interaction effect evaluating the difference in odds ratios of amnestic symptom between ADP and LRP groups also did not reach statistical significance. Conclusions The odds of specific initial cognitive symptoms differed between ADP and LRP among APOE ε4 carriers compared to non-carriers. The odds of initial amnestic symptom was higher among ADP APOE ε4 carriers and the odds of visuospatial initial symptom was higher with LRP APOE ε4 carriers. This supports the hypothesis that APOE ε4 differentially impacts initial cognitive symptoms together with underlying neuropathology.

scholarly journals Acute acetate administration increases endogenous opioid levels in the human brain: A [11C]carfentanil molecular imaging study

2021 ◽  
pp. 026988112096591
Author(s):  
Abhishekh H Ashok ◽  
Jim Myers ◽  
Gary Frost ◽  
Samuel Turton ◽  
Roger N Gunn ◽  
...  
Keyword(s):  
Human Brain ◽  
Sodium Acetate ◽  
Statistical Significance ◽  
Imaging Study ◽  
Pet Scan ◽  
Endogenous Opioid ◽  
Reference Tissue ◽  
Healthy Human ◽  
Fourfold Increase ◽  
Positron Emission

Introduction: A recent study has shown that acetate administration leads to a fourfold increase in the transcription of proopiomelanocortin (POMC) mRNA in the hypothalamus. POMC is cleaved to peptides, including β-endorphin, an endogenous opioid (EO) agonist that binds preferentially to the µ-opioid receptor (MOR). We hypothesised that an acetate challenge would increase the levels of EO in the human brain. We have previously demonstrated that increased EO release in the human brain can be detected using positron emission tomography (PET) with the selective MOR radioligand [11C]carfentanil. We used this approach to evaluate the effects of an acute acetate challenge on EO levels in the brain of healthy human volunteers. Methods: Seven volunteers each completed a baseline [11C]carfentanil PET scan followed by an administration of sodium acetate before a second [11C]carfentanil PET scan. Dynamic PET data were acquired over 90 minutes, and corrected for attenuation, scatter and subject motion. Regional [11C] carfentanil BPND values were then calculated using the simplified reference tissue model (with the occipital grey matter as the reference region). Change in regional EO concentration was evaluated as the change in [11C]carfentanil BPND following acetate administration. Results: Following sodium acetate administration, 2.5–6.5% reductions in [11C]carfentanil regional BPND were seen, with statistical significance reached in the cerebellum, temporal lobe, orbitofrontal cortex, striatum and thalamus. Conclusions: We have demonstrated that an acute acetate challenge has the potential to increase EO release in the human brain, providing a plausible mechanism of the central effects of acetate on appetite in humans.

scholarly journals Quantification of Ligand PET Studies using a Reference Region with a Displaceable Fraction: Application to Occupancy Studies with [11C]-DASB as an Example

2011 ◽  
Vol 32 (1) ◽  
pp. 70-80 ◽  
Author(s):  
Federico E Turkheimer ◽  
Sudhakar Selvaraj ◽  
Rainer Hinz ◽  
Venkatesha Murthy ◽  
Zubin Bhagwagar ◽  
...  
Keyword(s):  
Specific Binding ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Accurate Estimation ◽  
Data Sets ◽  
Reference Region ◽  
Reference Tissue ◽  
Positron Emission ◽  
Definition Of

This paper aims to build novel methodology for the use of a reference region with specific binding for the quantification of brain studies with radioligands and positron emission tomography (PET). In particular: (1) we introduce a definition of binding potential BPD = DVR–1 where DVR is the volume of distribution relative to a reference tissue that contains ligand in specifically bound form, (2) we validate a numerical methodology, rank-shaping regularization of exponential spectral analysis (RS-ESA), for the calculation of BPD that can cope with a reference region with specific bound ligand, (3) we demonstrate the use of RS-ESA for the accurate estimation of drug occupancies with the use of correction factors to account for the specific binding in the reference. [11C]-DASB with cerebellum as a reference was chosen as an example to validate the methodology. Two data sets were used; four normal subjects scanned after infusion of citalopram or placebo and further six test—retest data sets. In the drug occupancy study, the use of RS-ESA with cerebellar input plus corrections produced estimates of occupancy very close the ones obtained with plasma input. Test-retest results demonstrated a tight linear relationship between BPD calculated either with plasma or with a reference input and high reproducibility.

scholarly journals Newborns from deliveries with epidural anaesthesia

2010 ◽  
Vol 138 (3-4) ◽  
pp. 192-196
Author(s):  
Lidija Avramovic ◽  
Nedjo Cutura ◽  
Vesna Soldo ◽  
Aleksandar Curkovic ◽  
Tanja Lazic-Mitrovic
Keyword(s):  
Pregnant Woman ◽  
Epidural Anaesthesia ◽  
Apgar Score ◽  
Serum Proteins ◽  
Statistical Significance ◽  
Free Fraction ◽  
Control Group ◽  
Physiological Status ◽  
Vacuum Extractor ◽  
Foetal Circulation

Introduction. The use of epidural anaesthesia in delivery with the purpose to reduce pain and fear in a pregnant woman has the influence on the physiological status of the woman in childbirth and the course of delivery. From the epidural space of the pregnant woman, one part of free anaesthetic comes in the foetal circulation through the mother's circulation and placenta and connects with the foetal proteins. A lower value of albumins and serum proteins in the foetal circulation give bigger free fraction of anaesthetic which is accumulated in the foetal liver, brain and heart full of blood. Objective. The aim of the study was to examine the influence of epidural anaesthesia on the newborn. Methods. Retrospective study of 6,398 documents of newborns was performed in our Clinic of Gynaecology and Obstetrics 'Narodni front' during 2006. The first group was made of 455 newborns from deliveries with epidural anaesthesia and the second was the control group of 5,943 remaining newborns. In both groups we analysed the following: sex, week of gestation, weight, Apgar score, measure of care and resuscitation, perinatal morbidity and then the obtained results were compared. Results. Most of deliveries were vaginal without obstetric intervention (86.6%). The number of deliveries finished with vacuum extractor (4.6%) was statistically significantly bigger in the group with epidural anaesthesia than in the control group. Most of the newborns in the first group were born on time (96.5%) in 39.0?1.0 week of gestation and with foetal weight 3448?412 grammes. There was no statistical significance in Apgar score between both groups. Epidural anaesthesia does not increase the degree of the newborn's injury. Lower pH of blood was found in the newborns from deliveries with vacuum extractor or operated on (the Ceasarean section). Conclusion. Application of epidural anaesthesia decreases duration of delivery and has no adverse effects on the newborn and hypoxic encephalopathy is lower.

scholarly journals Test–retest variability and reference region-based quantification of 18F-BCPP-EF for imaging mitochondrial complex I in the human brain

2020 ◽  
pp. 0271678X2092814 ◽  
Author(s):  
Ayla Mansur ◽  
Eugenii A Rabiner ◽  
Hideo Tsukada ◽  
Robert A Comley ◽  
Yvonne Lewis ◽  
...  
Keyword(s):  
Complex I ◽  
Compartment Model ◽  
Mitochondrial Complex I ◽  
Reference Region ◽  
Mitochondrial Complex ◽  
Time Activity ◽  
Non Invasive ◽  
Arterial Blood ◽  
Absolute Test ◽  
Highly Correlated

Mitochondrial complex I (MC-I) is an essential regulator of brain bioenergetics and can be quantified in the brain using PET radioligand 18F-BCPP-EF. Here we evaluate the test–retest reproducibility of 18F-BCPP-EF in humans, and assess the use of a non-invasive quantification method (standardised uptake value ratio – SUVR). Thirty healthy volunteers had a 90-min dynamic 18F-BCPP-EF scan with arterial blood sampling, five of which received a second scan to be included in the test–retest analysis. Time-activity curves (TAC) were analysed using multilinear analysis 1 (MA1) and the two-tissue compartment model (2TC) to estimate volumes of distribution (VT). Regional SUVR-1 values were calculated from the 70 to 90-min TAC data using the centrum semiovale as a pseudo reference region, and compared to kinetic analysis-derived outcome measures. The mean absolute test–retest variability of VT ranged from 12% to 18% across regions. Both DVR-1and SUVR-1 had improved test–retest variability in the range 2%–7%. SUVR-1 was highly correlated with DVR-1 (r2 = 0.97, n = 30). In conclusion, 18F-BCPP-EF has suitable test–retest reproducibility and can be used to quantify MC-I in clinical studies.

scholarly journals Building a database for brain 18 kDa translocator protein imaged using [11C]PBR28 in healthy subjects

2018 ◽  
Vol 39 (6) ◽  
pp. 1138-1147 ◽  
Author(s):  
Soumen Paul ◽  
Evan Gallagher ◽  
Jeih-San Liow ◽  
Sanche Mabins ◽  
Katharine Henry ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
High Performance ◽  
Patient Characteristics ◽  
Brain Regions ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Blood Samples ◽  
Arterial Blood ◽  
Logan Plot ◽  
Translocator Protein 18 Kda

Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [11C]PBR28. In order to study the effects of age, sex, and obesity on TSPO binding and to determine whether this binding can be accurately assessed using fewer radio high-performance liquid chromatography (radio-HPLC) measurements of arterial blood samples, we created a database of 48 healthy subjects who had undergone [11C]PBR28 scans (23 high-affinity binders (HABs) and 25 mixed-affinity binders (MABs), 20 F/28 M, age: 40.6 ± 16.8 years). After analysis by Logan plot using 23 metabolite-corrected arterial samples, total distribution volume ( VT) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake ( VND) as 1.40 mL · cm−3, which generated a specific-to-nondisplaceable ratio ( BPND) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. VT increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, VT did not correlate with body mass index and was not affected by sex. These results underscore which patient characteristics should be accounted for during [11C]PBR28 studies and suggest ways to perform such studies more easily and with fewer blood samples.

scholarly journals Evaluation of Simplified Kinetic Analyses for Measurement of Brain Acetylcholinesterase Activity Using N-[11C]Methylpiperidin-4-yl Propionate and Positron Emission Tomography

2004 ◽  
Vol 24 (6) ◽  
pp. 600-611 ◽  
Author(s):  
Koichi Sato ◽  
Kiyoshi Fukushi ◽  
Hitoshi Shinotoh ◽  
Shinichiro Nagatsuka ◽  
Noriko Tanaka ◽  
...  
Keyword(s):  
Ache Activity ◽  
Arterial Input Function ◽  
Acetylcholinesterase Activity ◽  
Input Function ◽  
Previous Method ◽  
Target Tissue ◽  
Standard Analysis ◽  
Reference Tissue ◽  
Arterial Blood ◽  
Positron Emission

The applicability of two reference tissue-based analyses without arterial blood sampling for the measurement of brain regional acetylcholinesterase (AChE) activity using N-[11C]methylpiperidin-4-yl propionate ([11C]MP4P) was evaluated in 12 healthy subjects. One was a linear least squares analysis derived from Blomqvist's equation, and the other was the analysis of the ratio of target-tissue radioactivity relative to reference-tissue radioactivity proposed by Herholz and coworkers. The standard compartment analysis using arterial input function provided reliable quantification of k3 (an index of AChE activity) estimates in regions with low (neocortex and hippocampus), moderate (thalamus), and high (cerebellum) AChE activity with a coefficient of variation (COV) of 12% to 19%. However, the precise k3 value in the striatum, where AChE activity is the highest, was not obtained. The striatum was used as a reference because its time-radioactivity curve was proportional to the time integral of the arterial input function. Reliable k3 estimates were also obtained in regions with low-to-moderate AChE activity with a COV of less than 21% by striatal reference analyses, though not obtained in the cerebellum. Shape analysis, the previous method of direct k3 estimation from the shape of time-radioactivity data, gave k3 estimates in the cortex and thalamus with a somewhat larger COV. In comparison with the standard analysis, a moderate overestimation of k3 by 9% to 18% in the linear analysis and a moderate underestimation by 2% to 13% in the Herholz method were observed, which were appropriately explained by the results of computer simulation. In conclusion, simplified kinetic analyses are practical and useful for the routine analysis of clinical [11C]MP4P studies and are nearly as effective as the standard analysis for detecting regions with abnormal AChE activity.

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