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 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 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.

scholarly journals Parametric methods for [18F]flortaucipir PET

2018 ◽  
Vol 40 (2) ◽  
pp. 365-373 ◽  
Author(s):  
Sandeep SV Golla ◽  
Emma E Wolters ◽  
Tessa Timmers ◽  
Rik Ossenkoppele ◽  
Chris WJ van der Weijden ◽  
...  
Keyword(s):  
Specific Binding ◽  
Volume Ratio ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Distribution Volume ◽  
Binding Potential ◽  
Parametric Images ◽  
Distribution Volume Ratio ◽  
Pet Scans

[18F]Flortaucipir is a PET tau tracer used to visualize tau binding in Alzheimer’s disease (AD) in vivo. The present study evaluated the performance of several methods to obtain parametric images of [18F]flortaucipir. One hundred and thirty minutes dynamic PET scans were performed in 10 AD patients and 10 controls. Parametric images were generated using different linearization and basis function approaches. Regional binding potential (BPND) and volume of distribution (VT) values obtained from the parametric images were compared with corresponding values derived using the reversible two-tissue compartment model (2T4k_VB). Performance of SUVr parametric images was assessed by comparing values with distribution volume ratio (DVR) and SRTM-derived BPND estimates obtained using non-linear regression (NLR). Spectral analysis (SA) ( r2 = 0.92; slope = 0.99) derived VT correlated well with NLR-derived VT. RPM ( r2 = 0.95; slope = 0.98) derived BPND correlated well with NLR-derived DVR. Although SUVr80–100 min correlated well with NLR-derived DVR ( r2 = 0.91; slope = 1.09), bias in SUVr appeared to depend on uptake time and underlying level of specific binding. In conclusion, RPM and SA provide parametric images comparable to the NLR estimates. Individual SUVr values are biased compared with DVR and this bias requires further study in a larger dataset in order to understand its consequences.

Evaluation of [18F]-JNJ-64326067-AAA tau PET tracer in humans

2021 ◽  
pp. 0271678X2110310
Author(s):  
Suzanne L Baker ◽  
Karine Provost ◽  
Wesley Thomas ◽  
AJ Whitman ◽  
Mustafa Janabi ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Volume Ratio ◽  
Graphical Analysis ◽  
Pet Scan ◽  
Amyloid Pet ◽  
Reference Tissue ◽  
Pet Tracer ◽  
Significant Difference ◽  
Distribution Volume Ratio ◽  
Simplified Reference Tissue Model

The [18F]-JNJ-64326067-AAA ([18F]-JNJ-067) tau tracer was evaluated in healthy older controls (HCs), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and progressive supranuclear palsy (PSP) participants. Seventeen subjects (4 HCs, 5 MCIs, 5 ADs, and 3 PSPs) received a [11C]-PIB amyloid PET scan, and a tau [18F]-JNJ-067 PET scan 0-90 minutes post-injection. Only MCIs and ADs were amyloid positive. The simplified reference tissue model, Logan graphical analysis distribution volume ratio, and SUVR were evaluated for quantification. The [18F]-JNJ-067 tau signal relative to the reference region continued to increase to 90 min, indicating the tracer had not reached steady state. There was no significant difference in any bilateral ROIs for MCIs or PSPs relative to HCs; AD participants showed elevated tracer relative to controls in most cortical ROIs (P < 0.05). Only AD participants showed elevated retention in the entorhinal cortex. There was off-target signal in the putamen, pallidum, thalamus, midbrain, superior cerebellar gray, and white matter. [18F]-JNJ-067 significantly correlated (p < 0.05) with Mini-Mental State Exam in entorhinal cortex and temporal meta regions. There is clear binding of [18F]-JNJ-067 in AD participants. Lack of binding in HCs, MCIs and PSPs suggests [18F]-JNJ-067 may not bind to low levels of AD-related tau or 4 R tau.

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 Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography

2011 ◽  
Vol 31 (8) ◽  
pp. 1807-1816 ◽  
Author(s):  
Pablo M Rusjan ◽  
Alan A Wilson ◽  
Peter M Bloomfield ◽  
Irina Vitcu ◽  
Jeffrey H Meyer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Specific Binding ◽  
Compartment Model ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Specific Distribution ◽  
Positron Emission

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of VT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

scholarly journals Measurement of Regional Cerebral pH in Human Subjects Using Continuous Inhalation of 11CO2 and Positron Emission Tomography

1984 ◽  
Vol 4 (3) ◽  
pp. 458-465 ◽  
Author(s):  
David J. Brooks ◽  
Adriaan A. Lammertsma ◽  
Ronald P. Beaney ◽  
Klaus L. Leenders ◽  
Peter D. Buckingham ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Subjects ◽  
Compartment Model ◽  
Emission Tomography ◽  
Inhalation Technique ◽  
Positron Emission ◽  
Brain Ph ◽  
Normal Human ◽  
Uptake Data ◽  
Arterial Plasma

The cerebral pH of four normal human subjects has been measured using continuous inhalation of 11CO2 and positron emission tomography (PET). 11CO2 was administered to each subject at a constant rate for 15 min, during which time serial arterial plasma 11C levels were determined and serial 11C cerebral uptake PET scans were performed at a fixed axial tomographic level. 11C uptake kinetics were analysed using a three-compartment model. Rate constants have been estimated for the free exchange of 11CO2 between plasma and cerebral compartments for each subject, and their cerebral pH calculated. Whole brain pH values ranged from 6.96 to 7.05, and no significant pH difference between regions containing predominantly grey or white matter was noted. Best fits to 11C uptake data were achieved by effectively neglecting the metabolic fixation of 11C by cerebral tissue. The purpose of this study was to test the feasibility of pH measurement using the 11CO2 continuous inhalation technique. It is concluded from the results and the error analysis that continuous 11CO2 inhalation combined with PET is potentially a simple and useful method for determining regional cerebral pH.

scholarly journals A Strategy for Removing the Bias in the Graphical Analysis Method

2001 ◽  
Vol 21 (3) ◽  
pp. 307-320 ◽  
Author(s):  
Jean Logan ◽  
Joanna S. Fowler ◽  
Nora D. Volkow ◽  
Yu Shin Ding ◽  
Gene-Jack Wang ◽  
...  
Keyword(s):  
Least Squares ◽  
Graphical Method ◽  
Graphical Analysis ◽  
Distribution Volume ◽  
Noise Model ◽  
Data Sets ◽  
Multiple Time ◽  
Analysis Method ◽  
Reference Tissue ◽  
The One

The graphical analysis method, which transforms multiple time measurements of plasma and tissue uptake data into a linear plot, is a useful tool for rapidly obtaining information about the binding of radioligands used in PET studies. The strength of the method is that it does not require a particular model structure. However, a bias is introduced in the case of noisy data resulting in the underestimation of the distribution volume (DV), the slope obtained from the graphical method. To remove the bias, a modification of the method developed by Feng et al. (1993) , the generalized linear least squares (GLLS) method, which provides unbiased estimates for compartment models was used. The one compartment GLLS method has a relatively simple form, which was used to estimate the DV directly and as a smoothing technique for more general classes of model structures. In the latter case, the GLLS method was applied to the data in two parts, that is, one set of parameters was determined for times 0 to T1 and a second set from T1 to the end time. The curve generated from these two sets of parameters then was used as input to the graphical method. This has been tested using simulations of data similar to that of the PET ligand [11C]- d-threo-methylphenidate (MP, DV = 35 mL/mL) and 11C raclopride (RAC, DV = 1.92 mL/mL) and compared with two examples from image data with the same tracers. The noise model was based on counting statistics through the half-life of the isotope and the scanning time. Five hundred data sets at each noise level were analyzed. Results (DV) for the graphical analysis (DVg), the nonlinear least squares (NLS) method (DVnls), the one-tissue compartment GLLS method (DVf), and the two part GLLS followed by graphical analysis (DVfg) were compared. DVFG was found to increase somewhat with increasing noise and in some data sets at high noise levels no estimate could be obtained. However, at intermediate levels it provided a good estimation of the true DV. This method was extended to use a reference tissue in place of the input function to generate the distribution volume ratio (DVR) to the reference region. A linearized form of the simplified reference tissue method of Lammertsma and Hume (1996) was used. The DVR generated directly from the model (DVRfl) was compared with DVRfg (determined from a “smoothed” uptake curve as for DVfg) using the graphical method.

scholarly journals Multiple Linear Analysis Methods for the Quantification of Irreversibly Binding Radiotracers

2008 ◽  
Vol 28 (12) ◽  
pp. 1965-1977 ◽  
Author(s):  
Su Jin Kim ◽  
Jae Sung Lee ◽  
Yu Kyeong Kim ◽  
James Frost ◽  
Gary Wand ◽  
...  
Keyword(s):  
Statistical Power ◽  
Least Squares Method ◽  
Multiple Linear Regression Model ◽  
Nonlinear Least Squares ◽  
Compartment Model ◽  
Linear Analysis ◽  
Graphical Analysis ◽  
Least Square ◽  
Positron Emission ◽  
Nonlinear Least Squares Method

Gjedde—Patlak graphical analysis (GPGA) has commonly been used to quantify the net accumulations (Kin) of radioligands that bind or are taken up irreversibly. We suggest an alternative approach (MLAIR: multiple linear analysis for irreversible radiotracers) for the quantification of these types of tracers. Two multiple linear regression model equations were derived from differential equations of the two-tissue compartment model with irreversible binding. Multiple linear analysis for irreversible radiotracer 1 has a desirable feature for ordinary least square estimations because only the dependent variable CT( t) is noisy. Multiple linear analysis for irreversible radiotracer 2 provides Kin from direct estimates of the coefficients of independent variables without the mediation of a division operation. During computer simulations, MLAIR1 provided less biased Kin estimates than the other linear methods, but showed a high uncertainty level for noisy data, whereas MLAIR2 increased the robustness of estimation in terms of variability, but at the expense of increased bias. For real [11C]MeNTI positron emission tomography data, both methods showed good correlations, with parameters estimated using the standard nonlinear least squares method. Multiple linear analysis for irreversible radiotracer 2 parametric images showed remarkable image quality as compared with GPGA images. It also showed markedly improved statistical power for voxelwise comparisons than GPGA. The two MLAIR approaches examined were found to have several advantages over the conventional GPGA method.

scholarly journals Abnormal neuroinflammation in fibromyalgia and CRPS using [11C]-(R)-PK11195 PET

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246152
Author(s):  
Seongho Seo ◽  
Ye-Ha Jung ◽  
Dasom Lee ◽  
Won Joon Lee ◽  
Joon Hwan Jang ◽  
...  
Keyword(s):  
Primary Motor Cortex ◽  
Volume Ratio ◽  
Pain Syndrome ◽  
Superior Temporal Gyrus ◽  
Emission Tomography ◽  
Healthy Controls ◽  
Positron Emission ◽  
Postcentral Gyrus ◽  
Distribution Volume Ratio ◽  
Critical Regions

Purpose Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls. Methods Neuroinflammation was measured as the distribution volume ratio (DVR) of [11C]-(R)-PK11195 positron emission tomography (PET) in 12 FM patients, 11 patients with CRPS and 15 healthy controls. Results Neuroinflammation in FM patients was significantly higher in the left pre (primary motor cortex) and post (primary somatosensory cortex) central gyri (p < 0.001), right postcentral gyrus (p < 0.005), left superior parietal and superior frontal gyri (p < 0.005), left precuneus (p < 0.01), and left medial frontal gyrus (p = 0.036) compared with healthy controls. Furthermore, the DVR of [11C]-(R)-PK11195 in FM patients demonstrated decreased neuroinflammation in the medulla (p < 0.005), left superior temporal gyrus (p < 0.005), and left amygdala (p = 0.020) compared with healthy controls. Conclusions To the authors’ knowledge, this report is the first to describe abnormal neuroinflammation levels in the brains of FM patients compared with that in patients with CRPS using [11C]-(R)-PK11195 PET. The results suggested that abnormal neuroinflammation can be an important pathological factor in FM. In addition, the identification of common and different critical regions related to abnormal neuroinflammation in FM, compared with patients with CRPS and healthy controls, may contribute to improved diagnosis and the development of effective medical treatment for patients with FM.

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