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.

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.

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 with 18 F-Fallypride Positron Emission Tomography: Choice of Reference Region

2013 ◽  
Vol 12 (8) ◽  
pp. 7290.2013.00065 ◽  
Author(s):  
Kenji Ishibashi ◽  
Chelsea L. Robertson ◽  
Mark A. Mandelkern ◽  
Andrew T. Morgan ◽  
Edythe D. London
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Reference Region ◽  
Reference Tissue ◽  
Tissue Model ◽  
Positron Emission ◽  
Reference Tissue Model ◽  
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.

scholarly journals Comparative Assessment of Parametric Neuroreceptor Mapping Approaches Based on the Simplified Reference Tissue Model Using [11C]ABP688 PET

2015 ◽  
Vol 35 (12) ◽  
pp. 2098-2108 ◽  
Author(s):  
Seongho Seo ◽  
Su J Kim ◽  
Yu K Kim ◽  
Jee-Young Lee ◽  
Jae M Jeong ◽  
...  
Keyword(s):  
Least Squares ◽  
Nuclear Imaging ◽  
Volume Ratio ◽  
Parametric Image ◽  
Reference Tissue ◽  
Tissue Model ◽  
Positron Emission ◽  
Reference Tissue Model ◽  
Image Production ◽  
Simplified Reference Tissue Model

In recent years, several linearized model approaches for fast and reliable parametric neuroreceptor mapping based on dynamic nuclear imaging have been developed from the simplified reference tissue model (SRTM) equation. All the methods share the basic SRTM assumptions, but use different schemes to alleviate the effect of noise in dynamic-image voxels. Thus, this study aimed to compare those approaches in terms of their performance in parametric image generation. We used the basis function method and MRTM2 (multilinear reference tissue model with two parameters), which require a division process to obtain the distribution volume ratio (DVR). In addition, a linear model with the DVR as a model parameter (multilinear SRTM) was used in two forms: one based on linear least squares and the other based on extension of total least squares (TLS). Assessment using simulated and actual dynamic [11C]ABP688 positron emission tomography data revealed their equivalence with the SRTM, except for different noise susceptibilities. In the DVR image production, the two multilinear SRTM approaches achieved better image quality and regional compatibility with the SRTM than the others, with slightly better performance in the TLS-based method.

scholarly journals Comparison of Plasma Input and Reference Tissue Models for Analysing [11C]flumazenil Studies

2007 ◽  
Vol 28 (3) ◽  
pp. 579-587 ◽  
Author(s):  
Ursula MH Klumpers ◽  
Dick J Veltman ◽  
Ronald Boellaard ◽  
Emile F Comans ◽  
Cassandra Zuketto ◽  
...  
Keyword(s):  
White Matter ◽  
Rejection Rate ◽  
Compartment Model ◽  
Reference Tissue ◽  
Tissue Model ◽  
Arterial Blood ◽  
Positron Emission ◽  
Reference Tissue Model ◽  
Simplified Reference Tissue Model ◽  
Tissue Models

A single-tissue compartment model with plasma input is the established method for analysing [11C]flumazenil ([11C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been fully validated for [11C]FMZ. Dynamic [11C]FMZ positron emission tomography scans with arterial blood sampling were performed in nine drug-free depressive patients and eight healthy subjects. Regions of interest were defined on co-registered magnetic resonance imaging scans and projected onto dynamic [11C]FMZ images. Using a Hill-type metabolite function, single (1T) and reversible two-tissue (2T) compartmental models were compared. Simplified reference tissue model (SRTM) and full reference tissue model (FRTM) were investigated using both pons and (centrum semiovale) white matter as reference tissue. The 2T model provided the best fit in 59% of cases. Two-tissue VT values were on average 1.6% higher than 1T VT values. Owing to the higher rejection rate of 2T fits (7.3%), the 1T model was selected as plasma input method of choice. SRTM was superior to FRTM, irrespective whether pons or white matter was used as reference tissue. BPND values obtained with SRTM correlated strongly with 1T VT ( r = 0.998 and 0.995 for pons and white matter, respectively). Use of white matter as reference tissue resulted in 5.5% rejected fits, primarily in areas with intermediate receptor density. No fits were rejected using pons as reference tissue. Pons produced 23% higher BPND values than white matter. In conclusion, for most clinical studies, SRTM with pons as reference tissue can be used for quantifying [11C]FMZ binding.

Interictal Brain 5-HT1A Receptors Binding in Migraine Without Aura: A 18F-MPPF-PET Study

Cephalalgia ◽  
2008 ◽  
Vol 28 (12) ◽  
pp. 1282-1291 ◽  
Author(s):  
A Lothe ◽  
I Merlet ◽  
G Demarquay ◽  
N Costes ◽  
P Ryvlin ◽  
...  
Keyword(s):  
Cortical Excitability ◽  
Region Of Interest ◽  
Binding Potential ◽  
Resonance Imaging ◽  
Reference Tissue ◽  
Tissue Model ◽  
Positron Emission ◽  
Cortical Regions ◽  
Simplified Reference Tissue Model ◽  
The Brain

In this study we aimed to assess the brain distribution of 5-HT1A receptors in migraine patients without aura. Ten female migraine patients and 24 female healthy volunteers underwent magnetic resonance imaging and positron emission tomography using a radioligand antagonist of 5-HT1A receptors [4-(2'-methoxyphenyl)-1-[2'-( N-2-pirydynyl)-p-fluorobenzamido]-ethylpiperazine (18F-MPPF)]. A simplified reference tissue model was used to generate parametric images of 5-HT1A receptor binding potential (BP) values. Statistical Parametrical Mapping (SPM) analysis showed increased MPPF BP in posterior cortical areas and hippocampi bilaterally in patients compared with controls. Region of interest (ROI) analysis showed a non-significant trend in favour of a BP increase patients in cortical regions identified by the SPM analysis except in hippocampi, left parietal areas and raphe nuclei. During the interictal period of migraine patients without aura, the increase of MPPF BP in posterior cortical and limbic areas could reflect an increase in receptor density or a decrease of endogenous serotonin, which could explain their altered cortical excitability.

scholarly journals Long-Term Test–Retest Reliability of Striatal and Extrastriatal Dopamine D2/3 Receptor Binding: Study with [11C]Raclopride and High-Resolution PET

2015 ◽  
Vol 35 (7) ◽  
pp. 1199-1205 ◽  
Author(s):  
Kati Alakurtti ◽  
Jarkko J Johansson ◽  
Juho Joutsa ◽  
Matti Laine ◽  
Lars Bäckman ◽  
...  
Keyword(s):  
High Resolution ◽  
Intraclass Correlation ◽  
Binding Potential ◽  
Reference Tissue ◽  
Retest Reliability ◽  
Positron Emission ◽  
Simplified Reference Tissue Model ◽  
Test Retest Reliability

We measured the long-term test–retest reliability of [11C]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [11C]raclopride assessments, with a 5-week retest interval. D2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test–retest studies of [11C]raclopride binding in the striatum. A novel finding is the relatively low variability of [11C]raclopride binding, providing suggestive evidence that extrastriatal D2/3 binding can be studied in vivo with [11C]raclopride PET to be verified in future studies.

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