Optimal experiment design for PET quantification of receptor concentration

Muzic, Raymond F.; Nelson, A.D.; Saidel, Gerald M.; Miraldi, Floro

doi:10.1109/42.481436

Cited by 20 publications

(27 citation statements)

References 33 publications

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“…The experimental protocols require specification of ligand dosages and injection times (MuzIc et al, 1996). Previous optimal experiment designs that consider ligand dosages and injection times separately (DELFORGE et al, 1989) may not yield an overall optimal design.…”

Section: Si(t) -mentioning

confidence: 99%

“…in the present work, we have studied a representative fiadrenergic receptor system in pig ventricular myocardium and have applied a pharmacokinetic model (MuzIc et al, 1996) to interpret the PET data in terms of the underlying ligand-receptor system characteristics. This model describes ligand haemodynamics, ligand-receptor interactions and several secondary factors affecting the PET data.…”

Section: Si(t) -mentioning

confidence: 99%

See 1 more Smart Citation

Iterative optimal design of PET experiments for estimating β-adrenergic receptor concentration

Muzic

Saidel

Zhu

et al. 2000

Med. Biol. Eng. Comput.

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To estimate in vivo myocardial beta-adrenergic receptor concentration with sufficient precision and to reduce the experimental complexities in positron emission tomography (PET), an iterative optimal design method is applied. An initial three-injection protocol, utilising [F-18]-labelled (R)- and (S)-fluorocarazolol and unlabelled (S)-fluorocarazolol, is optimised for ligand dosages and administration times to maximise the precision of all model parameters using the D-optimal criterion. Using this experimental protocol, PET data are collected in porcine studies, and model parameters are estimated. All model parameters are identified with satisfactory precision. The in vivo myocardial beta-receptor concentration is 7.5+/-0.6 pmol x ml(-1), which corresponds to the in vitro result of 10.1+/-1.3 pmol x ml(-1). With more accurate parameter values, a simplified two-injection protocol is optimally designed, utilising only radiolabelled and unlabelled (S)-fluorocarazolol, based on a new criterion to maximise the precision of the beta-receptor concentration. This revised optimum design predicts that the in vivo beta-receptor concentration can be estimated with good precision but reduced experiment complexity.

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Section: Si(t) -mentioning

confidence: 99%

Section: Si(t) -mentioning

confidence: 99%

Iterative optimal design of PET experiments for estimating β-adrenergic receptor concentration

Muzic

Saidel

Zhu

et al. 2000

Med. Biol. Eng. Comput.

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show abstract

“…Along these lines, multiple injections of tracer at different specific activities have been administered during a single scan session (Christian et al, 2004;Delforge et al, 1989Delforge et al, , 1990Huang et al, 1989;Millet et al, 2000;Morris et al, 1996a;Morris et al, 1996b;Muzic et al, 1996). Multiple injection approaches facilitate observation of the system at multiple operating points; model fitting of all the data simultaneously leads to improved identifiability of parameters.…”

Section: Introductionmentioning

confidence: 99%

Estimating neurotransmitter kinetics with ntPET: A simulation study of temporal precision and effects of biased data

Normandin

Morris

2008

NeuroImage

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We recently introduced ntPET (neurotransmitter PET), an analysis technique which estimates the kinetics of stimulus-induced neurotransmitter (NT) release. Here, we evaluate two formulations of ntPET. The arterial (ART) approach measures the tracer input function (TIF) directly. The reference (REF) approach derives the TIF from reference region data. Arterial sampling is considered the gold standard in PET modeling but reference region approaches are preferred for reduced cost and complexity. If simulated PET data with unbiased TIFs were analyzed using ART or REF, temporal precision was better than three minutes provided NT concentration peaked less than 30 minutes into the scanning session. The consequences of biased TIFs or stimulus-induced changes in tracer delivery were also evaluated. ART TIFs were biased by the presence of uncorrected radiometabolites in the plasma whereas REF TIFs were biased by specific binding in the reference region. Simulated changes in tracer delivery emulated ethanol-induced blood flow alterations observed previously with PET (Volkow et al., 1988). ART performance deteriorated significantly if metabolites amounted to 50% of plasma radioactivity by 60 minutes. The accuracy and precision of REF were preserved even if the reference region contained 40% of the receptor density of the target region. Both methods were insensitive to blood flow alterations (proportional changes in K 1 and k 2 ). Our results suggest that PET data contain information -heretofore not extracted -about the timing of NT release. The REF formulation of ntPET proved to be robust to many plausible model violations and under most circumstances is an appropriate alternative to ART.

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“…The Nelder-Mead algorithm is a popular (Press et al, 1992) local search approach which in at least one previous case (Muzic et al, 1996) has been successfully applied to experiment design.…”

Section: Design Optimization : Two Algorithmsmentioning

confidence: 99%

“…This task falls within the class of problems often referred to as optimal experiment design, a field which has proponents in both geophysics (Maurer and Boerner, 1998;Curtis, 1999a,b;Stummer et al, 2002;van den Berg et al, 2003;Curtis et al, 2004;Routh et al, 2005) and the broader scientific community (Box and Lucas, 1959;John and Draper, 1975;Walter and Pronzato, 1987;Muzic et al, 1996). When searching for an optimal experiment several considerations rapidly become apparent, mainly what "optimal" means in the context of geophysical measurements.…”

Section: Introductionmentioning

confidence: 99%

Optimal experiment design for time-lapse traveltime tomography

Ajo‐Franklin

2009

GEOPHYSICS

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Geophysical monitoring techniques offer the only noninvasive approach capable of assessing both the spatial and temporal dynamics of subsurface fluid processes. Increasingly, permanent sensor arrays in boreholes and on the ocean floor are being deployed to improve the repeatability and increase the temporal sampling of monitoring surveys. Because permanent arrays require a large up-front capital investment and are difficult (or impossible) to re-configure once installed, a premium is placed on selecting a geometry capable of imaging the desired target at minimum cost. We present a simple approach to optimizing downhole sensor configurations for monitoring experiments making 1 use of differential seismic traveltimes. In our case, we use a design quality metric based on the accuracy of tomographic reconstructions for a suite of imaging targets. By not requiring an explicit singular value decomposition of the forward operator, evaluation of this objective function scales to problems with a large number of unknowns. We also restrict the design problem by recasting the array geometry into a low dimensional form more suitable for optimization at a reasonable computational cost. We test two search algorithms on the design problem: the Nelder-Mead downhill simplex method and the Multilevel Coordinate Search algorithm. The algorithm is tested for four crosswell acquisition scenarios relevant to continuous seismic monitoring, a two parameter array optimization, several scenarios involving four parameter length/offset optimizations, and a comparison of optimal multi-source designs. In the last case, we also examine trade-offs between source sparsity and the quality of tomographic reconstructions. One general observation is that asymmetric array lengths improve localized image quality in crosswell experiments with a small number of sources and a large number of receivers. Preliminary results also suggest that highquality differential images can be generated using only a small number of optimally positioned sources.2

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Optimal experiment design for PET quantification of receptor concentration

Cited by 20 publications

References 33 publications

Iterative optimal design of PET experiments for estimating β-adrenergic receptor concentration

Iterative optimal design of PET experiments for estimating β-adrenergic receptor concentration

Estimating neurotransmitter kinetics with ntPET: A simulation study of temporal precision and effects of biased data

Optimal experiment design for time-lapse traveltime tomography

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