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Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. (Nuclear Medicine and PET)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi. (Nuclear Medicine and PET)
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
Vise andre og tillknytning
2019 (engelsk)Inngår i: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 22, artikkel-id 101681Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

[F-18]THK5317 is a PET tracer for in-vivo imaging of tau associated with Alzheimer's disease (AD). This work aimed to evaluate optimal timing for standardized uptake value ratio (SUVR) measures with [F-18]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R-1) parametric images. Nine AD patients and nine controls underwent 90 min [F-18]THK5317 scans. SUVR-1 was calculated at transient equilibrium (TE) and for seven different 20 min intervals and compared with distribution volume ratio (DVR; reference Logan). Cerebellar grey matter (MRI) was used as reference region. A supervised cluster analysis (SVCA) method was implemented to automatically generate a reference region, directly from the dynamic PET volume without the need of a structural MRI scan, for computation of SUVR-1 and R-1 images for a scan duration matching the optimal timing. TE was reached first in putamen, frontal- and parietal cortex at 22 +/- 4 min for AD patients and in putamen at 20 +/- 0 min in controls. Over all regions and subjects, SUVR20-40-1 correlated best with DVR-1, R-2 = 0.97. High correlation was found between values generated using MRI- and SVCA-based reference (R-2 = 0.93 for SUVR20-40-1; R-2 = 0.94 for R-1). SUVR20-40 allows for accurate semi-quantitative assessment of tau pathology and SVCA may be used to obtain a reference region for calculation of both SUVR-1 and R-1 with 40 min scan duration.

sted, utgiver, år, opplag, sider
2019. Vol. 22, artikkel-id 101681
Emneord [en]
Alzheimer’s disease, PET, Parametric images, Supervised clustering, Tau imaging
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-341785DOI: 10.1016/j.nicl.2019.101681ISI: 000470123000005PubMedID: 30710871OAI: oai:DiVA.org:uu-341785DiVA, id: diva2:1182858
Forskningsfinansiär
Swedish Research Council, 05817The Swedish Brain FoundationStockholm County CouncilThe Karolinska Institutet's Research FoundationGun och Bertil Stohnes StiftelseStiftelsen Gamla TjänarinnorSwedish Foundation for Strategic Research Tilgjengelig fra: 2018-02-14 Laget: 2018-02-14 Sist oppdatert: 2024-01-17bibliografisk kontrollert
Inngår i avhandling
1. Towards Clinical Implementation of Dynamic Positron Emission Tomography in Neurodegenerative Diseases
Åpne denne publikasjonen i ny fane eller vindu >>Towards Clinical Implementation of Dynamic Positron Emission Tomography in Neurodegenerative Diseases
2018 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2018. s. 55
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1429
Emneord
Positron emission tomography, PET, Molecular imaging, Quantification, Kinetic modelling, Parametric images, Alzheimer’s disease, Parkinson’s disease
HSV kategori
Forskningsprogram
Radiologi
Identifikatorer
urn:nbn:se:uu:diva-341786 (URN)978-91-513-0238-6 (ISBN)
Disputas
2018-04-06, Skoogsalen, Akademiska Sjukhuset, Ing 79, Uppsala, 09:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2018-03-14 Laget: 2018-02-15 Sist oppdatert: 2018-04-24

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