scholarly journals Model-Free Quantification of Dynamic PET Data Using Nonparametric Deconvolution

2015 ◽  
Vol 35 (8) ◽  
pp. 1368-1379 ◽  
Author(s):  
Francesca Zanderigo ◽  
Ramin V Parsey ◽  
R Todd Ogden
Keyword(s):  
Impulse Response Function ◽  
Input Function ◽  
Volume Of Distribution ◽  
Emission Tomography ◽  
Tracer Kinetics ◽  
Model Free ◽  
Positron Emission ◽  
Way 100635 ◽  
Value Decomposition ◽  
Free Quantification

Dynamic positron emission tomography (PET) data are usually quantified using compartment models (CMs) or derived graphical approaches. Often, however, CMs either do not properly describe the tracer kinetics, or are not identifiable, leading to nonphysiologic estimates of the tracer binding. The PET data are modeled as the convolution of the metabolite-corrected input function and the tracer impulse response function (IRF) in the tissue. Using nonparametric deconvolution methods, it is possible to obtain model-free estimates of the IRF, from which functionals related to tracer volume of distribution and binding may be computed, but this approach has rarely been applied in PET. Here, we apply nonparametric deconvolution using singular value decomposition to simulated and test–retest clinical PET data with four reversible tracers well characterized by CMs ([11C]CUMI-101, [11C]DASB, [11C]PE2I, and [11C]WAY-100635), and systematically compare reproducibility, reliability, and identifiability of various IRF-derived functionals with that of traditional CMs outcomes. Results show that nonparametric deconvolution, completely free of any model assumptions, allows for estimates of tracer volume of distribution and binding that are very close to the estimates obtained with CMs and, in some cases, show better test–retest performance than CMs outcomes.

scholarly journals In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation

2019 ◽  
Vol 116 (23) ◽  
pp. 11490-11495 ◽  
Author(s):  
Margaret T. Davis ◽  
Ansel Hillmer ◽  
Sophie E. Holmes ◽  
Robert H. Pietrzak ◽  
Nicole DellaGioia ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Suicide Risk ◽  
Potential Role ◽  
Input Function ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Regions Of Interest ◽  
Emission Tomography ◽  
Positron Emission

Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) to compare with that of healthy comparison controls (HC; n = 29). Volume of distribution was computed using a venous input function in the five key frontal and limbic brain regions. We observed significantly higher mGluR5 availability in PTSD compared with HC individuals in all regions of interest (P’s = 0.001–0.01) and compared with MDD individuals in three regions (P’s = 0.007). mGluR5 availability was not significantly different between MDD and HC individuals (P = 0.17). Importantly, we observed an up-regulation in mGluR5 availability in the PTSD-SI group (P’s = 0.001–0.007) compared with PTSD individuals without SI. Findings point to the potential role for mGluR5 as a target for intervention and, potentially, suicide risk management in PTSD.

scholarly journals A Two-Compartment Description and Kinetic Procedure for Measuring Regional Cerebral [11C]Nomifensine Uptake Using Positron Emission Tomography

1990 ◽  
Vol 10 (3) ◽  
pp. 307-316 ◽  
Author(s):  
Eric Salmon ◽  
David J. Brooks ◽  
Klaus L. Leenders ◽  
David R. Turton ◽  
Sue P. Hume ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Partition Coefficient ◽  
Cell Activity ◽  
Compartment Model ◽  
Input Function ◽  
Volume Of Distribution ◽  
Red Cells ◽  
Emission Tomography ◽  
Binding Potential ◽  
Positron Emission

S-[11C]Nomifensine ( S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood–brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a “free” NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its “binding potential” to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers.

scholarly journals The Influence of Tissue Heterogeneity on Results of Fitting Nonlinear Model Equations to Regional Tracer Uptake Curves: With an Application to Compartmental Models Used in Positron Emission Tomography

1987 ◽  
Vol 7 (2) ◽  
pp. 214-229 ◽  
Author(s):  
K. Herholz ◽  
C. S. Patlak
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Glucose Metabolism ◽  
Capillary Permeability ◽  
Input Function ◽  
Tracer Uptake ◽  
Compartmental Models ◽  
Emission Tomography ◽  
Tissue Heterogeneity ◽  
Positron Emission

An analytical method based on Taylor expansions was developed to analyze errors caused by tissue heterogeneity in dynamic positron emission tomography (PET) measurements. Some general rules concerning the effect of parameter variances and covariances were derived. The method was further applied to various compartmental models currently used for measurement of blood flow, capillary permeability, glucose metabolism, and tracer binding. Blood flow and capillary permeability are shown to be generally underestimated in heterogenous tissue, the underestimation being more severe for slowly decaying, constant or increasing input functions rather than for bolus input, and increasing with measurement time. Typical errors caused by the heterogeneity due to insufficient separation between gray and white matter by a PET scanner with full width at half-maximum (FWHM)= 5 to 10 mm resolution range between–0.9 and–6% in dynamic CBF measurements with intravenous (i. v.) bolus injection of 15O-water or inhalation of 18F-fluoromethane and total measurement times of6 or 10 min, respectively. Binding or metabolic rates determined with tracers that are essentially trapped in tissue (e.g., FDG for measurement of cerebral glucose metabolism) are only slightly overestimated (0.5–3.0%) at typical measurement times and are essentially independent of the shape of the input function. The error increases considerably if tracer accumulation is very slow, however, or if short measurement times [<5/(k2 + k3)] are used. Some rate constants are also subject to larger errors.

scholarly journals Image-Derived Input Function for Brain PET Studies: Many Challenges and Few Opportunities

2011 ◽  
Vol 31 (10) ◽  
pp. 1986-1998 ◽  
Author(s):  
Paolo Zanotti-Fregonara ◽  
Kewei Chen ◽  
Jeih-San Liow ◽  
Masahiro Fujita ◽  
Robert B Innis
Keyword(s):  
Invasive Procedure ◽  
Input Function ◽  
Emission Tomography ◽  
Alternative Methods ◽  
Less Invasive ◽  
Brain Pet ◽  
Positron Emission ◽  
Arterial Sampling ◽  
Challenging Technique ◽  
Methodological Problems

Quantitative positron emission tomography (PET) brain studies often require that the input function be measured, typically via arterial cannulation. Image-derived input function (IDIF) is an elegant and attractive noninvasive alternative to arterial sampling. However, IDIF is also a very challenging technique associated with several problems that must be overcome before it can be successfully implemented in clinical practice. As a result, IDIF is rarely used as a tool to reduce invasiveness in patients. The aim of the present review was to identify the methodological problems that hinder widespread use of IDIF in PET brain studies. We conclude that IDIF can be successfully implemented only with a minority of PET tracers. Even in those cases, it only rarely translates into a less-invasive procedure for the patient. Finally, we discuss some possible alternative methods for obtaining less-invasive input function.

scholarly journals Measurement of Changes in Opioid Receptor Binding in Vivo During Trigeminal Neuralgic Pain Using [11C]Diprenorphine and Positron Emission Tomography

1999 ◽  
Vol 19 (7) ◽  
pp. 803-808 ◽  
Author(s):  
Anthony K. P. Jones ◽  
Niel D. Kitchen ◽  
Hiroshi Watabe ◽  
Vincent J. Cunningham ◽  
Terry Jones ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Volume Of Distribution ◽  
Emission Tomography ◽  
Subcortical Structures ◽  
Endogenous Opioid ◽  
Positron Emission ◽  
Before And After ◽  
Pain State ◽  
Parietal Cortices

The binding of [11C]diprenorphine to µ, κ, and Δ subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.

scholarly journals Measuring Drug Occupancy in the Absence of a Reference Region: The Lassen Plot Re-Visited

2009 ◽  
Vol 30 (1) ◽  
pp. 46-50 ◽  
Author(s):  
Vincent J Cunningham ◽  
Eugenii A Rabiner ◽  
Mark Slifstein ◽  
Marc Laruelle ◽  
Roger N Gunn
Keyword(s):  
Graphical Method ◽  
Quantitative Estimation ◽  
Specific Binding ◽  
Volume Of Distribution ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Reference Region ◽  
Site Specific ◽  
Positron Emission ◽  
Regional Estimates

Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution ( VT) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand ( VND) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of VT alone to determine occupancy, together with an extension that does not require baseline data.

scholarly journals Positron Emission Tomography/Magnetic Resonance Hybrid Scanner Imaging of Cerebral Blood Flow Using 15O-Water Positron Emission Tomography and Arterial Spin Labeling Magnetic Resonance Imaging in Newborn Piglets

2015 ◽  
Vol 35 (11) ◽  
pp. 1703-1710 ◽  
Author(s):  
Julie B Andersen ◽  
William S Henning ◽  
Ulrich Lindberg ◽  
Claes N Ladefoged ◽  
Liselotte Højgaard ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Magnetic Resonance ◽  
Arterial Spin Labeling ◽  
Input Function ◽  
Emission Tomography ◽  
Resonance Imaging ◽  
Newborn Piglets ◽  
Positron Emission

Abnormality in cerebral blood flow (CBF) distribution can lead to hypoxic–ischemic cerebral damage in newborn infants. The aim of the study was to investigate minimally invasive approaches to measure CBF by comparing simultaneous 15O-water positron emission tomography (PET) and single TI pulsed arterial spin labeling (ASL) magnetic resonance imaging (MR) on a hybrid PET/MR in seven newborn piglets. Positron emission tomography was performed with IV injections of 20 MBq and 100 MBq 15O-water to confirm CBF reliability at low activity. Cerebral blood flow was quantified using a one-tissue-compartment-model using two input functions: an arterial input function (AIF) or an image-derived input function (IDIF). The mean global CBF (95% CI) PET-AIF, PET-IDIF, and ASL at baseline were 27 (23; 32), 34 (31; 37), and 27 (22; 32) mL/100 g per minute, respectively. At acetazolamide stimulus, PET-AIF, PET-IDIF, and ASL were 64 (55; 74), 76 (70; 83) and 79 (67; 92) mL/100 g per minute, respectively. At baseline, differences between PET-AIF, PET-IDIF, and ASL were 22% ( P < 0.0001) and −0.7% ( P = 0.9). At acetazolamide, differences between PET-AIF, PET-IDIF, and ASL were 19% ( P = 0.001) and 24% ( P = 0.0003). In conclusion, PET-IDIF overestimated CBF. Injected activity of 20 MBq 15O-water had acceptable concordance with 100 MBq, without compromising image quality. Single TI ASL was questionable for regional CBF measurements. Global ASL CBF and PET CBF were congruent during baseline but not during hyperperfusion.

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