scholarly journals Estimation of drug receptor occupancy when non-displaceable binding differs between brain regions - extending the simplified reference tissue model

2015 ◽  
Vol 80 (1) ◽  
pp. 116-127
Author(s):  
Matts Kågedal ◽  
Katarina Varnäs ◽  
Andrew C. Hooker ◽  
Mats O. Karlsson
Keyword(s):  
Receptor Occupancy ◽  
Brain Regions ◽  
Reference Tissue ◽  
Tissue Model ◽  
Reference Tissue Model ◽  
Drug Receptor ◽  
Simplified Reference Tissue Model

scholarly journals Dual time-point imaging for post-dose binding potential estimation applied to a [11C]raclopride PET dose occupancy study

2016 ◽  
Vol 37 (3) ◽  
pp. 866-876
Author(s):  
Isadora L Alves ◽  
Antoon TM Willemsen ◽  
Rudi A Dierckx ◽  
Ana Maria M da Silva ◽  
Michel Koole
Keyword(s):  
Receptor Occupancy ◽  
Standard Uptake Value ◽  
Binding Potential ◽  
Post Dose ◽  
Reference Tissue ◽  
Tissue Model ◽  
Reference Tissue Model ◽  
Dual Time Point ◽  
Simplified Reference Tissue Model ◽  
Time Point

Receptor occupancy studies performed with PET often require time-consuming dynamic imaging for baseline and post-dose scans. Shorter protocol approximations based on standard uptake value ratios have been proposed. However, such methods depend on the time-point chosen for the quantification and often lead to overestimation and bias. The aim of this study was to develop a shorter protocol for the quantification of post-dose scans using a dual time-point approximation, which employs kinetic parameters from the baseline scan. Dual time-point was evaluated for a [11C]raclopride PET dose occupancy study with the D2 antagonist JNJ-37822681, obtaining estimates for binding potential and receptor occupancy. Results were compared to standard simplified reference tissue model and standard uptake value ratios-based estimates. Linear regression and Bland–Altman analysis demonstrated excellent correlation and agreement between dual time-point and the standard simplified reference tissue model approach. Moreover, the stability of dual time-point-based estimates is shown to be independent of the time-point chosen for quantification. Therefore, a dual time-point imaging protocol can be applied to post-dose [11C]raclopride PET scans, resulting in a significant reduction in total acquisition time while maintaining accuracy in the quantification of both the binding potential and the receptor occupancy.

An extended simplified reference tissue model for the quantification of dynamic PET with amphetamine challenge

NeuroImage ◽  
2006 ◽  
Vol 33 (2) ◽  
pp. 550-563 ◽  
Author(s):  
Yun Zhou ◽  
Ming-Kai Chen ◽  
Christopher J. Endres ◽  
Weiguo Ye ◽  
James R. Brašić ◽  
...  
Keyword(s):  
Dynamic Pet ◽  
Reference Tissue ◽  
Tissue Model ◽  
Reference Tissue Model ◽  
Simplified Reference Tissue Model

A reference tissue forward model for improved PET accuracy using within-scan displacement studies

2021 ◽  
pp. 0271678X2110652
Author(s):  
Joseph B Mandeville ◽  
Michael A Levine ◽  
John T Arsenault ◽  
Wim Vanduffel ◽  
Bruce R Rosen ◽  
...  
Keyword(s):  
Radioactive Decay ◽  
Forward Model ◽  
Binding Potential ◽  
Reference Tissue ◽  
Primate Model ◽  
Tissue Model ◽  
Pet Tracer ◽  
Reference Tissue Model ◽  
Simplified Reference Tissue Model ◽  
Improved Accuracy

We report a novel forward-model implementation of the full reference tissue model (fFTRM) that addresses the fast-exchange approximation employed by the simplified reference tissue model (SRTM) by incorporating a non-zero dissociation time constant from the specifically bound compartment. The forward computational approach avoided errors associated with noisy and nonorthogonal basis functions using an inverse linear model. Compared to analysis by a multilinear single-compartment reference tissue model (MRTM), fFTRM provided improved accuracy for estimation of binding potentials at early times in the scan, with no worse reproducibility across sessions. To test the model’s ability to identify small focal changes in binding potential using a within-scan challenge, we employed a nonhuman primate model of focal dopamine release elicited by deep brain microstimulation remote to ventral striatum (VST) during imaging by simultaneous PET and fMRI. The new model reported an unambiguously lateralized response in VST consistent with fMRI, whereas the MRTM-derived response was not lateralized and was consistent with simulations of model bias. The proposed model enabled better accuracy in PET [11C]raclopride displacement studies and may also facilitate challenges sooner after injection, thereby recovering some sensitivity lost to radioactive decay of the PET tracer.

The simplified reference tissue model for SPECT/PET brain receptor studies

2008 ◽  
Vol 47 (04) ◽  
pp. 167-174 ◽  
Author(s):  
F. Thiele ◽  
R. Buchert
Keyword(s):  
Region Of Interest ◽  
Compartment Model ◽  
Receptor Imaging ◽  
Reference Tissue ◽  
Time Activity ◽  
Tissue Model ◽  
Activity Curve ◽  
Reference Tissue Model ◽  
Simplified Reference Tissue Model ◽  
Brain Receptor

SummaryAim: The SRTM (simplified reference tissue model) of brain receptor imaging assumes that the time activity curve in the receptor-rich region of interest can be fitted satisfactorily by the 1-tissue compartment model. This assumption has been formulated by a rather restrictive constraint on the rate constants. Empirically, the SRTM might well describe also tracers which do not fulfil this constraint, such as [11C]raclopride, for example. However, this has not been justified rigorously. Methods: The requirements for the SRTM to be applicable are analyzed in detail. Results: The SRTM is applicable under a less restrictive constraint than described previously. The interpretation of the SRTM parameters R1 and K2 in physiological terms depends on the constraint, while the interpretation of BPND does not. Conclusion: Correct interpretation of the results of the SRTM is tracer specific. In particular, the parameter R1, which in case of compliance with the original constraint might be used to detect perfusion and/or extraction effects, might not be appropriate for this purpose in case of raclopride-like tracers.

scholarly journals Noise Reduction in the Simplified Reference Tissue Model for Neuroreceptor Functional Imaging

2002 ◽  
Vol 22 (12) ◽  
pp. 1440-1452 ◽  
Author(s):  
Yanjun Wu ◽  
Richard E. Carson
Keyword(s):  
Noise Reduction ◽  
Compartment Model ◽  
Binding Potential ◽  
Reference Region ◽  
Reference Tissue ◽  
Tissue Model ◽  
Tissue Compartment ◽  
Functional Images ◽  
Reference Tissue Model ◽  
Simplified Reference Tissue Model

The Simplified Reference Tissue Model (SRTM) produces functional images of receptor binding parameters using an input function derived from a reference region and assuming a model with one tissue compartment. Three parameters are estimated: binding potential ( BP), relative delivery ( R1), and the reference region clearance constant k′2 Since k′2 should not vary across brain pixels, the authors developed a two-step method (SRTM2) using a global value of k′2. Whole-brain simulations were performed using human input functions and rate constants for [18F]FCWAY, [11C]flumazenil, and [11C]raclopride, and parameter SD and bias were determined for SRTM and SRTM2. The global mean of k′2 was slightly biased (2% to 6%), but the median was unbiased (<1%) and was used as the global value. Binding potential noise reductions with SRTM2 were 4% to 14%, 20% to 53%, and 10% to 30% for [18F]FCWAY, [11C]flumazenil, and [11C]raclopride, respectively, with larger reductions for shorter scans. R1 noise reduction was larger than that of BP. Simulations were also performed to assess bias when the reference and/or tissue regions followed a two-tissue compartment model. Owing to the constrained k′2, SRTM2 showed somewhat larger biases due to violations of the one-compartment model assumption. These studies demonstrate that SRTM2 should be a useful method to improve the quality of neuroreceptor functional images.

scholarly journals The Simplified Reference Tissue Model: Model Assumption Violations and Their Impact on Binding Potential

2014 ◽  
Vol 35 (2) ◽  
pp. 304-311 ◽  
Author(s):  
Cristian A Salinas ◽  
Graham E Searle ◽  
Roger N Gunn
Keyword(s):  
Input Function ◽  
Binding Potential ◽  
Model Assumption ◽  
Reference Tissue ◽  
Tissue Model ◽  
Positron Emission ◽  
Assumption Violations ◽  
Quantitative Accuracy ◽  
Reference Tissue Model ◽  
Simplified Reference Tissue Model

Reference tissue models have gained significant traction over the last two decades as the methods of choice for the quantification of brain positron emission tomography data because they balance quantitative accuracy with less invasive procedures. The principal advantage is the elimination of the need to perform arterial cannulation of the subject to measure blood and metabolite concentrations for input function generation. In particular, the simplified reference tissue model (SRTM) has been widely adopted as it uses a simplified model configuration with only three parameters that typically produces good fits to the kinetic data and a stable parameter estimation process. However, the model's simplicity and its ability to generate good fits to the data, even when the model assumptions are not met, can lead to misplaced confidence in binding potential (BPND) estimates. Computer simulation were used to study the bias introduced in BPND estimates as a consequence of violating each of the four core SRTM model assumptions. Violation of each model assumption led to bias in BPND (both over and underestimation). Careful assessment of the bias in SRTM BPND should be performed for new tracers and applications so that an appropriate decision about its applicability can be made.

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