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      Mapping 18F-FDG Kinetics Together with Patient-Specific Bootstrap Assessment of Uncertainties: An Illustration with Data from a PET/CT Scanner with a Long Axial Field of View

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          Abstract

          The purpose of this study was to examine a nonparametric approach to mapping kinetic parameters and their uncertainties with data from the emerging generation of dynamic whole-body PET/CT scanners. Methods: Dynamic PET 18F-FDG data from a set of 24 cancer patients studied on a long-axial-field-of-view PET/CT scanner were considered. Kinetics were mapped using a nonparametric residue mapping (NPRM) technique. Uncertainties were evaluated using an image-based bootstrapping methodology. Kinetics and bootstrap-derived uncertainties are reported for voxels, maximum-intensity projections, and volumes of interest (VOIs) corresponding to several key organs and lesions. Comparisons between NPRM and standard 2-compartment (2C) modeling of VOI kinetics are carefully examined. Results: NPRM-generated kinetic maps were of good quality and well aligned with vascular and metabolic 18F-FDG patterns, reasonable for the range of VOIs considered. On a single 3.2-GHz processor, the specification of the bootstrapping model took 140 min; individual bootstrap replicates required 80 min each. VOI time-course data were much more accurately represented, particularly in the early time course, by NPRM than by 2C modeling constructs, and improvements in fit were statistically highly significant. Although 18F-FDG flux values evaluated by NPRM and 2C modeling were generally similar, significant deviations between vascular blood and distribution volume estimates were found. The bootstrap enables the assessment of quite complex summaries of mapped kinetics. This is illustrated with maximum-intensity maps of kinetics and their uncertainties. Conclusion: NPRM kinetics combined with image-domain bootstrapping is practical with large whole-body dynamic 18F-FDG datasets. The information provided by bootstrapping could support more sophisticated uses of PET biomarkers used in clinical decision-making for the individual patient.

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          Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data.

          C Patlak, R G Blasberg, J Fenstermacher (1983)
          A theoretical model of blood-brain exchange is developed and a procedure is derived that can be used for graphing multiple-time tissue uptake data and determining whether a unidirectional transfer process was dominant during part or all of the experimental period. If the graph indicates unidirectionality of uptake, then an influx constant (Ki) can be calculated. The model is general, assumes linear transfer kinetics, and consists of a blood-plasma compartment, a reversible tissue region with an arbitrary number of compartments, and one or more irreversible tissue regions. The solution of the equations for this model shows that a graph of the ratio of the total tissue solute concentration at the times of sampling to the plasma concentration at the respective times (Cp) versus the ratio of the arterial plasma concentration-time integral to Cp should be drawn. If the data are consistent with this model, then this graph will yield a curve that eventually becomes linear, with a slope of Ki and an ordinate intercept less than or equal to the vascular plus steady-state space of the reversible tissue region.
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            Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method.

            C Selin, Justin Huang, Björn Kuhl … (1979)
            Tracer techniques and quantitative autoradiographic and tissue counting models for measurement of metabolic rates were combined with positron computed tomography (PCT) and (F-18)2-fluoro-2-deoxy-D-glucose (FDG) for the measurement of local cerebral metabolic rate for glucose (LCMRGlc) in humans. A three-compartment model, which incorporates hydrolysis of FDG-6-PO4 to FDG, was developed for the measure of kinetic constants and calculation of LCMRGlc. Our model is an extension of that developed by Sokoloff et al. Although small, hydrolysis of FDG-6-PO4 was found to be significant. A PCT system, the ECAT, was used to determine the rate constants, lumped constant, and stability of the model in human beings. The data indicate that cerebral FDG-6-PO4 in humans increases for about 90 minutes, plateaus, and then slowly decreases. After 10 minutes, cerebral blood FDG activity levels were found to be a minor fraction of tissue activity. Precursor pool turnover rate, distribution volumes, and red blood cell-plasma concentration ratios were determined. Reproducibility (precision) of LCMRGlc measurements (approximate 2 cm2 regions) was +/- 5.5% over a 5-hour period. The replacement of arterial blood sampling with venous sampling was validated.
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              Performance Characteristics of the Biograph Vision Quadra PET/CT System with a Long Axial Field of View Using the NEMA NU 2-2018 Standard

              George A Prenosil, Hasan Sari, Markus Fürstner … (2022)
              Our purpose was to evaluate the performance of the Biograph Vision Quadra PET/CT system. This new system is based on the Biograph Vision 600, using the same silicon photomultiplier-based detectors with 3.2 × 3.2 × 20 mm lutetium-oxoorthosilicate crystals. The 32 detector rings of the Quadra provide a 4-fold larger axial field of view (AFOV) of 106 cm, enabling imaging of major organs in 1 bed position. Methods: The physical performance of the scanner was evaluated according to the National Electrical Manufacturers Association NU 2-2018 standard, with additional experiments to characterize energy resolution. Image quality was assessed with foreground-to-background ratios of 4:1 and 8:1. Additionally, a clinical 18F-FDG PET study was reconstructed with varying frame durations. In all experiments, data were acquired using the maximum ring distance of 322 crystals (MRD 322), whereas image reconstructions could be performed with a maximum ring distance of only 85 crystals (MRD 85). Results: The spatial resolution at full width at half maximum in the radial, tangential, and axial directions was 3.3, 3.4, and 3.8 mm, respectively. The sensitivity was 83 cps/kBq for MRD 85 and 176 cps/kBq for MRD 322. The noise-equivalent count rates (NECRs) at peak were 1,613 kcps for MRD 85 and 2,956 kcps for MRD 322, both at 27.49 kBq/mL. The respective scatter fractions at peak NECR equaled 36% and 37%. The time-of-flight resolution at peak NECR was 228 ps for MRD 85 and 230 ps for MRD 322. Image contrast recovery ranged from 69.6% to 86.9% for 4:1 contrast ratios and from 77.7% to 92.6% for 8:1 contrast ratios reconstructed using point-spread function time of flight with 8 iterations and 5 subsets. Thirty-second frames provided readable lesion detectability and acceptable noise levels in clinical images. Conclusion: The Biograph Vision Quadra PET/CT device has spatial and time resolution similar to those of the Biograph Vision 600 but exhibits improved sensitivity and NECR because of its extended AFOV. The reported spatial resolution, time resolution, and sensitivity make it a competitive new device in the class of PET scanners with an extended AFOV.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Nucl Med
                Journal ID (iso-abbrev): J Nucl Med
                Journal ID (hwp): jnumed
                Journal ID (publisher-id): jnm
                Title: Journal of Nuclear Medicine
                Publisher: Society of Nuclear Medicine
                ISSN (Print): 0161-5505
                ISSN (Electronic): 1535-5667
                Publication date (Print): June 2024
                Publication date PMC-release: June 2024
                Volume: 65
                Issue: 6
                Pages: 971-979
                Affiliations
                [1 ]Department of Statistics, School of Mathematical Sciences, University College Cork, Cork, Ireland;
                [2 ]Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland; and
                [3 ]Department of Nuclear Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
                Author notes
                For correspondence or reprints, contact Finbarr O’Sullivan ( f.osullivan@ 123456ucc.ie ).

                Published online Apr. 11, 2024.

                Article
                Publisher ID: 266686
                DOI: 10.2967/jnumed.123.266686
                PMC ID: 11149602
                PubMed ID: 38604759
                SO-VID: eae92e5b-a266-4fff-82f3-ba20878b5afb
                Copyright © © 2024 by the Society of Nuclear Medicine and Molecular Imaging.
                License:

                Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: http://jnm.snmjournals.org/site/misc/permission.xhtml.

                History
                Date received : 17 September 2023
                Date revision received : 13 February 2024
                Page count
                Pages: 9
                Categories
                Subject: Basic Science Investigation

                Keywords: dynamic pet studies,kinetic mapping,image-domain bootstrap,uncertainty assessment,compartment model
                Data availability:
                Keywords: dynamic pet studies, kinetic mapping, image-domain bootstrap, uncertainty assessment, compartment model

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