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Validation of parametric methods for [(11)C]PE2I positron emission tomography
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
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2013 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 74, p. 172-178Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES

The radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in vivo for investigation of changes in DAT concentration, progression of disease and validation of treatment using positron emission tomography (PET). DAT is an important protein for regulation of central dopamine concentration and DAT deficiency has been associated with several neurodegenerative and neuropsychiatric disorders. Accurate parametric images are a prerequisite for clinical application of [(11)C]PE2I. The purpose of this study was to evaluate different methods for producing [(11)C]PE2I parametric images, showing binding potential (BPND) and relative delivery (R1) at the voxel level, using clinical data as well as simulations.

METHODS

Investigations were made in twelve subjects either with social anxiety disorder (n=6) or parkinsonian syndrome (n=6), each receiving an 80min dynamic PET scan. All subjects underwent a T1-weighted MRI scan which was co-registered to the PET images and used for definition of regions of interest using a probabilistic template (PVElab). Two basis function implementations (receptor parametric mapping: RPM, RPM2) of the simplified reference tissue model (SRTM) and three multilinear reference tissue models (MRTMo, MRTM and MRTM2) were used for computation of parametric BPND and R1 images. In addition, reference Logan and standard uptake value ratio (SUVr) were investigated. Evaluations of BPND and R1 images were performed using linear regression to compare the parametric methods to region-based analyses with SRTM and cerebellar gray matter as reference region. Accuracy and precision of each method were assessed by simulations.

RESULTS

Correlation and slope of linear regression between parametric and region-based BPND and R1 values in both striatum and extra-striatal regions were optimal for RPM (R(2)=0.99 for both BPND and R1; slopes 0.99 and 0.98 for BPND and R1, respectively, in striatum). In addition, accuracy and precision were best for RPM and RPM2.

CONCLUSION

The basis function methods provided more robust estimations of the parameters compared to the other models and performed best in simulations. RPM, a basis function implementation of SRTM, is the preferred method for voxel level analysis of [(11)C]PE2I PET studies.

Place, publisher, year, edition, pages
2013. Vol. 74, p. 172-178
National Category
Neurology
Research subject
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-197228DOI: 10.1016/j.neuroimage.2013.02.022ISI: 000317441300018PubMedID: 23435214OAI: oai:DiVA.org:uu-197228DiVA, id: diva2:612549
Available from: 2013-03-22 Created: 2013-03-19 Last updated: 2018-02-15Bibliographically approved
In thesis
1. Towards Clinical Implementation of Dynamic Positron Emission Tomography in Neurodegenerative Diseases
Open this publication in new window or tab >>Towards Clinical Implementation of Dynamic Positron Emission Tomography in Neurodegenerative Diseases
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders worldwide. Positron emission tomography (PET), together with suitable biomarkers, can aid in the clin-ical evaluation as well as in research investigations of these diseases. Straightforward and quantitative assessments of the parameters of inter-est estimated on a voxel-level, as parametric images, are possible when PET data is acquired over time. Prerequisites to facilitate clinical use of dynamic PET are simplified analysis methods and scan protocols suita-ble for clinical routine.

The aim of this thesis was to validate simplified analysis methods, suitable for clinical use, for quantification of dopamine transporter (DAT) availability in patients with parkinsonism using [11C]PE2I PET and tau accumulation in AD patients with [18F]THK5317 PET.

The included subjects comprised of both healthy controls and pa-tients with parkinsonism, AD or mild cognitive impairment and each subject underwent a dynamic PET scan with either [11C]PE2I or [18F]THK5317. Models for quantitative voxel-based analysis, resulting in parametric images of tracer binding and overall brain function, were validated in both patients and controls. These parametric methods were compared to region-based values acquired using both plasma- and refer-ence-input models. Clinically feasible scan durations were evaluated for both [11C]PE2I and [18F]THK5317, and a clustering method to obtain a reference time activity curve directly from the dynamic PET data was validated. Furthermore, images of DAT availability and overall brain functional activity, generated from one single dynamic [11C]PE2I PET scan, were compared to a dual-scan approach using [123I]FP-CIT single photon emission computed tomography (SPECT) and [18F]FDG PET, for differential diagnosis of patient with parkinsonism.

Study I-III supply valuable information on the feasibility of dynamic [11C]PE2I in a clinical setting for differential diagnosis of parkinsonian disorders, by having easily accessible images of DAT availability and overall brain functional activity. The work in study IV-V showed that reference methods can be used for quantification of tau accumulation, and suggests that simplified analysis methods and shorter scan durations can be applied to further facilitate applications of dynamic [18F]THK5317 PET.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 55
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1429
Keyword
Positron emission tomography, PET, Molecular imaging, Quantification, Kinetic modelling, Parametric images, Alzheimer’s disease, Parkinson’s disease
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-341786 (URN)978-91-513-0238-6 (ISBN)
Public defence
2018-04-06, Skoogsalen, Akademiska Sjukhuset, Ing 79, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2018-03-14 Created: 2018-02-15 Last updated: 2018-04-24

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Jonasson, MyAppel, LieuweEngman, JonasFrick, AndreasNyholm, DagAskmark, HåkanDanfors, TorstenSörensen, JensFurmark, TomasLubberink, Mark

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