Positron emission tomography in the assessment of left ventricular function in healthy rats: A comparison of four imaging methods

Todica, Andrei; Böning, Guido; Lehner, S.; Weidl, Elaine; Cumming, Paul; Wängler, Carmen; Nekolla, SG; Schwaiger, Markus; Bartenstein, Peter; Schirrmacher, Ralf; Hacker, Marcus

doi:10.1007/s12350-012-9663-1

Cited by 15 publications

(21 citation statements)

References 31 publications

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“…The raw conduction (volume) signal is recorded in volts, therefor the predicted EDV is used to convert the peak voltage for each cardiac cycle to the maximum volume and the predicted SV is used to scale the amplitude of the voltage signal. fits (using (1) to literature data from catheter [33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52] and MRI-based measurement modalities [34,35,37,39,40,41,42,44,47,48,49,50,51]. Error bars denote the standard deviation from each study.…”

Section: Volume-conductance Calibrationmentioning

confidence: 99%

Practical identifiability and uncertainty quantification of a pulsatile cardiovascular model

Marquis

Arnold

Dean-Bernhoft

et al. 2018

Mathematical Biosciences

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Mathematical models are essential tools to study how the cardiovascular system maintains homeostasis. The utility of such models is limited by the accuracy of their predictions, which can be determined by uncertainty quantification (UQ). A challenge associated with the use of UQ is that many published methods assume that the underlying model is identifiable (e.g. that a one-to-one mapping exists from the parameter space to the model output). In this study we present a novel workflow to calibrate a lumped-parameter model to left ventricular pressure and volume time series data. Key steps include using (1) literature and available data to determine nominal parameter values; (2) sensitivity analysis and subset selection to determine a set of identifiable parameters; (3) optimization to find a point estimate for identifiable parameters; and (4) frequentist and Bayesian UQ calculations to assess the predictive capability of the model. Our results show that it is possible to determine 5 identifiable model parameters that can be estimated to our experimental data from three rats, and that computed UQ intervals capture the measurement and model error.

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Section: Volume-conductance Calibrationmentioning

confidence: 99%

Practical identifiability and uncertainty quantification of a pulsatile cardiovascular model

Marquis

Arnold

Dean-Bernhoft

et al. 2018

Mathematical Biosciences

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“…Finally, many different methods for labeling serum albumins and other compounds with fluorine-18 for PET blood pool imaging have been reported [6–10]. While any of these methods might offer some advantages in certain circumstances, these methods do not appear to meet simultaneously the criteria for pre-clinical and clinical blood pool imaging we have set forth.…”

Section: Discussionmentioning

confidence: 99%

“…However, while a variety of PET blood pool labels have been developed [6–10], no PET blood volume imaging agent is today in general widespread use for routine measurement and visualization of regional blood volume in either clinical or animal studies. Accordingly, the goal of the present work was to identify and synthesize a blood pool-imaging agent with potential for commercialization and wide-spread use in both clinical and animal PET imaging applications.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging

Basuli¹,

Li²,

Xu³

et al. 2015

Nuclear Medicine and Biology

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We sought to develop a practical, reproducible and clinically translatable method of radiolabeling serum albumins with fluorine-18 for use as a PET blood pool imaging agent in animals and man. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [18F]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [18F]tetrabutylammonium fluoride ([18F]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [18F]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH 9) for 15 min at 37–40 °C produced fluorine-18-radiolabeled RSA and the product was purified using a mini-PD MiniTrap G-25 column. The overall radiochemical yield of the reaction was 18–35% (n = 30, uncorrected) in a 90-min synthesis. This procedure, repeated with human serum albumin (HSA), yielded similar results. Fluorine-18-radiolabeled RSA demonstrated prolonged blood retention (biological half-life of 4.8 hours) in healthy awake rats. The distribution of major organ radioactivity remained relatively unchanged during the 4 hour observation periods either by direct tissue counting or by dynamic PET whole-body imaging except for a gradual accumulation of labeled metabolic products in the bladder. This manual method for synthesizing radiolabeled serum albumins uses fluorine-18, a widely available PET radionuclide, and natural protein available in both pure and recombinant forms which could be scaled up for widespread clinical applications. These preclinical biodistribution and PET imaging results indicate that [18F]RSA is an effective blood pool imaging agent in rats and might, as [18F]HSA, prove similarly useful as a clinical imaging agent.

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“…The feasibility of cardiac output and stroke volume (SV) estimations at first-pass by means of the Stewart-Hamilton indicator-dilution principle has already been demonstrated using either 82 Rb [ 18 ], 18 FDG [ 19 ], or 15 O-water PET [ 20 ], the provided estimates being in close agreement with those of RBC-SPECT, echocardiography, and CMR. Todica et al described LV volume and function measurements in healthy rats using first-pass gated 18 FDG PET [ 21 ], without significant difference compared to CMR in terms of ejection fraction. Such cardiac function assessment using first-pass gated PET has been poorly investigated in humans since only two studies are reported on the feasibility of LV function assessment using first-pass gated 15 O-water PET [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Feasibility of biventricular volume and function assessment using first-pass gated 15O-water PET

et al. 2018

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BackgroundWe investigated the feasibility of left ventricular (LV) and right ventricular (RV) volume and function estimation using a first-pass gated 15O-water PET. This prospective study included 19 patients addressed for myocardial perfusion reserve assessment using 15O-water PET. PET data were acquired at rest and after regadenoson stress, and gated first-pass images were reconstructed over the time range corresponding to tracer first-pass through the cardiac cavities and post-processed using TomPool software; LV and RV were segmented using a semi-automated 4D immersion algorithm. LV volumes were computed using a count-based model and a fixed threshold at 30% of the maximal activity. RV volumes were computed using a geometrical model and an adjustable threshold that was set so as to fit LV and RV stroke volumes. Ejection curves were fitted using a deformable reference curve model. LV results were compared to those obtained using 99mTc-sestamibi gated myocardial SPECT in terms of end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF).ResultsThere was an excellent concordance between rest and stress PET in terms of EDV and ESV (Lin’s coefficient ~ 0.85–0.90), SV (~ 0.80), and EF (~ 0.75) for both ventricles. Correlation with myocardial SPECT was high for LV EDV (Pearson’s R = 0.89, p < 0.001) and ESV (R = 0.87, p < 0.001) and satisfying for LV SV (R = 0.67, p < 0.001) and EF (R = 0.67, p < 0.001). Minimal LV ESV overestimation (+ 4 mL, p = 0.03) and EF underestimation (− 4%, p = 0.01) were observed using PET.ConclusionsBiventricular volume and function assessment are achievable using the first-pass PET, and LV parameters correlate well with those derived from gated myocardial SPECT.

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Positron emission tomography in the assessment of left ventricular function in healthy rats: A comparison of four imaging methods

Abstract: Relative to reference standard MRI measurements of LVEF, there was excellent agreement between PET-based measurements, notably for the novel blood-pool tracer (68)Ga-albumin.

Cited by 15 publications

References 31 publications

Practical identifiability and uncertainty quantification of a pulsatile cardiovascular model

Practical identifiability and uncertainty quantification of a pulsatile cardiovascular model

Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging

Feasibility of biventricular volume and function assessment using first-pass gated 15O-water PET

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