scholarly journals Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data

1996 ◽  
Vol 16 (5) ◽  
pp. 834-840 ◽  
Author(s):  
Jean Logan ◽  
Joanna S. Fowler ◽  
Nora D. Volkow ◽  
Gene-Jack Wang ◽  
Yu-Shin Ding ◽  
...  
Keyword(s):  
Arterial Input Function ◽  
Kinetic Constant ◽  
Volume Ratio ◽  
Input Function ◽  
Graphical Analysis ◽  
Distribution Volume ◽  
Blood Sampling ◽  
Average Percentage ◽  
Percentage Difference ◽  
Positron Emission

The distribution volume ratio (DVR), which is a linear function of receptor availability, is widely used as a model parameter in imaging studies. The DVR corresponds to the ratio of the DV of a receptor-containing region to a nonreceptor region and generally requires the measurement of an arterial input function. Here we propose a graphical method for determining the DVR that does not require blood sampling. This method uses data from a nonreceptor region with an average tissue-to-plasma efflux constant k2 to approximate the plasma integral. Data from positron emission tomography studies with [15C]raclopride (n = 20) and [11C] d-threo-methylphenidate ([11C]dMP) (n = 8) in which plasma data were taken and used to compare results from two graphical methods, one that uses plasma data and one that does not. k2 was 0.163 and 0.051 min−1 for [11C]raclopride and [11C]dMP, respectively. Results from both methods were very similar, and the average percentage difference between the methods was −0.11% for [11C]raclopride and 0.46% for [11C]dMP for DVR of basal ganglia (BG) to cerebellum (CB). Good agreement between the two methods was also achieved for DVR images created by both methods. This technique provides an alternative method of analysis not requiring blood sampling that gives equivalent results for the two ligands studied. It requires initial studies with blood sampling to determine the average kinetic constant and to test applicability. In some cases, it may be possible to neglect the b̅2 term if the BG/CB ratio becomes reasonably constant for a sufficiently long period of time over the course of the experiment.

scholarly journals The Use of Alternative Forms of Graphical Analysis to Balance Bias and Precision in PET Images

2010 ◽  
Vol 31 (2) ◽  
pp. 535-546 ◽  
Author(s):  
Jean Logan ◽  
David Alexoff ◽  
Joanna S Fowler
Keyword(s):  
Volume Ratio ◽  
Image Data ◽  
Compartment Model ◽  
Graphical Analysis ◽  
Distribution Volume ◽  
Good Precision ◽  
Reference Tissue ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
Uptake Data

Graphical analysis (GA) is an efficient method for estimating total tissue distribution volume ( VT) from positron emission tomography (PET) uptake data. The original GA produces a negative bias in VT in the presence of noise. Estimates of VT using other GA forms have less bias but less precision. Here, we show how the bias terms are related between the GA methods and how using an instrumental variable (IV) can also reduce bias. Results are based on simulations of a two-compartment model with VT's ranging from 10.5 to 64 mL/cm3 and from PET image data with the tracer [11C]DASB ([11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl) benzonitrile). Four estimates of VT (or distribution volume ratio (DVR) using a reference tissue) can be easily computed from different formulations of GA including the IV. As noise affects the estimates from all four differently, they generally do not provide the same estimates. By taking the median value of the four estimates, we can decrease the bias and reduce the effect of large values contributing to noisy images. The variance of the four estimates can serve as a guide to the reliability of the median estimate. This may provide a general method for the generation of parametric images with little bias and good precision.

scholarly journals Noninvasive Quantification of Cerebral Metabolic Rate for Glucose in Rats Using 18F-FDG PET and Standard Input Function

2015 ◽  
Vol 35 (10) ◽  
pp. 1664-1670 ◽  
Author(s):  
Yuki Hori ◽  
Naoki Ihara ◽  
Noboru Teramoto ◽  
Masako Kunimi ◽  
Manabu Honda ◽  
...  
Keyword(s):  
Metabolic Rate ◽  
Repeated Measures ◽  
Arterial Input Function ◽  
Area Under The Curve ◽  
Input Function ◽  
Blood Sampling ◽  
Cerebral Metabolic Rate ◽  
Positron Emission ◽  
The Individual ◽  
Individual Input

Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed 18F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIFNS) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF1S). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIFNS-, and EIF1S-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIFNS was highly correlated with those derived from AIF and EIF1S. Preliminary comparison between AIF and EIFNS in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIFNS method might serve as a noninvasive substitute for individual AIF measurement.

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.

scholarly journals Arterial Input Function Derived from Pairwise Correlations Between PET-image Voxels

2013 ◽  
Vol 33 (7) ◽  
pp. 1058-1065 ◽  
Author(s):  
Martin Schain ◽  
Simon Benjaminsson ◽  
Katarina Varnäs ◽  
Anton Forsberg ◽  
Christer Halldin ◽  
...  
Keyword(s):  
Arterial Input Function ◽  
Pearson Correlation ◽  
Invasive Procedure ◽  
Compartmental Analysis ◽  
Input Function ◽  
Time Activity ◽  
Pairwise Correlation ◽  
Positron Emission ◽  
Using Data ◽  
Suitable Reference

A metabolite corrected arterial input function is a prerequisite for quantification of positron emission tomography (PET) data by compartmental analysis. This quantitative approach is also necessary for radioligands without suitable reference regions in brain. The measurement is laborious and requires cannulation of a peripheral artery, a procedure that can be associated with patient discomfort and potential adverse events. A non invasive procedure for obtaining the arterial input function is thus preferable. In this study, we present a novel method to obtain image-derived input functions (IDIFs). The method is based on calculation of the Pearson correlation coefficient between the time-activity curves of voxel pairs in the PET image to localize voxels displaying blood-like behavior. The method was evaluated using data obtained in human studies with the radioligands [ 11 C]flumazenil and [ 11 C]AZ10419369, and its performance was compared with three previously published methods. The distribution volumes ( VT) obtained using IDIFs were compared with those obtained using traditional arterial measurements. Overall, the agreement in VT was good (~3% difference) for input functions obtained using the pairwise correlation approach. This approach performed similarly or even better than the other methods, and could be considered in applied clinical studies. Applications to other radioligands are needed for further verification.

scholarly journals Quantification of [18F]florbetapir: A test–retest tracer kinetic modelling study

2018 ◽  
Vol 39 (11) ◽  
pp. 2172-2180 ◽  
Author(s):  
Sandeep SV Golla ◽  
Sander CJ Verfaillie ◽  
Ronald Boellaard ◽  
Sofie M Adriaanse ◽  
Marissa D Zwan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Volume Ratio ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Retest Reliability ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
Test Retest Reliability

Accumulation of amyloid beta can be visualized using [18F]florbetapir positron emission tomography. The aim of this study was to identify the optimal model for quantifying [18F]florbetapir uptake and to assess test–retest reliability of corresponding outcome measures. Eight Alzheimer’s disease patients (age: 67 ± 6 years, Mini-Mental State Examination (MMSE): 23 ± 3) and eight controls (age: 63 ± 4 years, MMSE: 30 ± 0) were included. Ninety-minute dynamic positron emission tomography scans, together with arterial blood sampling, were acquired immediately following a bolus injection of 294 ± 32 MBq [18F]florbetapir. Several plasma input models and the simplified reference tissue model (SRTM) were evaluated. The Akaike information criterion was used to identify the preferred kinetic model. Compared to controls, Alzheimer’s disease patients had lower MMSE scores and evidence for cortical Aβ pathology. A reversible two-tissue compartment model with fitted blood volume fraction (2T4k_VB) was the preferred model for describing [18F]florbetapir kinetics. SRTM-derived non-displaceable binding potential (BPND) correlated well (r2 = 0.83, slope = 0.86) with plasma input-derived distribution volume ratio. Test–retest reliability for plasma input-derived distribution volume ratio, SRTM-derived BPND and SUVr(50–70) were r = 0.88, r = 0.91 and r = 0.86, respectively. In vivo kinetics of [18F]florbetapir could best be described by a reversible two-tissue compartmental model and [18F]florbetapir BPND can be reliably estimated using an SRTM.

scholarly journals Quantitative Analysis for Estimating Binding Potential of the Brain Serotonin Transporter with [11C]McN5652

2002 ◽  
Vol 22 (4) ◽  
pp. 490-501 ◽  
Author(s):  
Yoko Ikoma ◽  
Tetsuya Suhara ◽  
Hinako Toyama ◽  
Tetsuya Ichimiya ◽  
Akihiro Takano ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Arterial Input Function ◽  
Volume Ratio ◽  
Least Square Method ◽  
Distribution Volume ◽  
Least Square ◽  
Binding Potential ◽  
Nonspecific Binding ◽  
Distribution Volume Ratio

[11C](+)McN5652 is a selective serotonin reuptake inhibitor with subnanomolar potency for the serotonin transporter, and is currently being used for positron emission tomography studies. However, quantification of the regional [11C](+)McN5652 binding potential in vivo is a controversial issue because of its complex characteristics. The authors examined the regional differences in nonspecific binding and proposed simple methods for estimating the binding potential of [11C](+)McN5652. The regional difference in nonspecific binding was evaluated by the activity ratio of the thalamus compared with the cerebellum for inactive-isomer [11C](−)McN5652 and [11C](+)McN5652 saturation studies. The distribution volume of the thalamus was approximately 1.16 times larger than that of the cerebellum. The thalamus-to-cerebellum distribution volume ratio was estimated by nonlinear least square and graphical methods, with and without arterial input function. The graphical method with k2′ without blood sampling was practical and most applicable for estimation of the distribution volume ratio because this method is more stable than the nonlinear least square method in the simulation study. Binding potential estimated with the distribution volume ratio of [11C](+)McN5652 and the correction with distribution volume ratio of [11C](−)McN5652 represent the most reliable parameters for the assessment of serotonin transporter binding.

scholarly journals In-vivo Measurement of LDOPA Uptake, Dopamine Reserve and Turnover in the Rat Brain Using [18F]FDOPA PET

2012 ◽  
Vol 33 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Matthew D Walker ◽  
Katherine Dinelle ◽  
Rick Kornelsen ◽  
Siobhan McCormick ◽  
Chenoa Mah ◽  
...  
Keyword(s):  
Volume Ratio ◽  
Distribution Volume ◽  
Binding Potential ◽  
In Vivo Measurement ◽  
Longitudinal Measurements ◽  
Positron Emission ◽  
Distribution Volume Ratio ◽  
6 Hydroxydopamine ◽  
Effective Distribution

Longitudinal measurements of dopamine (DA) uptake and turnover in transgenic rodents may be critical when developing disease-modifying therapies for Parkinson's disease (PD). We demonstrate methodology for such measurements using [18F]fluoro-3,4-dihydroxyphenyl- L-alanine ([18F]FDOPA) positron emission tomography (PET). The method was applied to 6-hydroxydopamine lesioned rats, providing the first PET-derived estimates of DA turnover for this species. Control ( n = 4) and unilaterally lesioned ( n = 11) rats were imaged multiple times. Kinetic modeling was performed using extended Patlak, incorporating a kloss term for metabolite washout, and modified Logan methods. Dopaminergic terminal loss was measured via [11C]-(+)-dihydrotetrabenazine (DTBZ) PET. Clear striatal [18F]FDOPA uptake was observed. In the lesioned striatum the effective DA turnover increased, shown by a reduced effective distribution volume ratio ( EDVR) for [18F]FDOPA. Effective distribution volume ratio correlated ( r > 0.9) with the [11C]DTBZ binding potential ( BPND). The uptake and trapping rate ( kref) decreased after lesioning, but relatively less so than [11C]DTBZ BPND. For normal controls, striatal estimates were kref = 0.037 ± 0.005 per minute, EDVR = 1.07 ± 0.22 and kloss = 0.024 ± 0.003 per minute (30 minutes turnover half-time), with repeatability (coefficient of variation) ≤11%. [18F]fluoro-3,4-dihydroxyphenyl- L-alanine PET enables measurements of DA turnover in the rat, which is useful for developing novel therapies for PD.

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