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Jonasson, My
Publications (10 of 25) Show all publications
Jonasson, M., Wall, A., Chiotis, K., Leuzy, A., Eriksson, J., Antoni, G., . . . Lubberink, M. (2019). Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET.. NeuroImage: Clinical, 22, Article ID 101681.
Open this publication in new window or tab >>Optimal timing of tau pathology imaging and automatic extraction of a reference region using dynamic [18F]THK5317 PET.
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2019 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 22, article id 101681Article in journal (Refereed) Published
Abstract [en]

[18F]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 [18F]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R1) parametric images. Nine AD patients and nine controls underwent 90 min [18F]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 R1 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, R2 = 0.97. High correlation was found between values generated using MRI- and SVCA-based reference (R2 = 0.93 for SUVR20-40-1; R2 = 0.94 for R1). 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 R1 with 40 min scan duration.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Alzheimer's disease, PET, Parametric images, Supervised clustering, Tau imaging
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-382941 (URN)10.1016/j.nicl.2019.101681 (DOI)000470123000005 ()30710871 (PubMedID)
Funder
Swedish Research Council, 05817Stockholm County CouncilGun och Bertil Stohnes StiftelseThe Karolinska Institutet's Research FoundationThe Swedish Brain FoundationSwedish Foundation for Strategic Research EU, FP7, Seventh Framework Programme
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-26Bibliographically approved
Motilla Hoppe, J., Frick, A., Åhs, F., Linnman, C., Appel, L., Jonasson, M., . . . Furmark, T. (2018). Association between amygdala neurokinin-1 receptor availability and anxiety-related personality traits. Translational Psychiatry, 8(1), 168
Open this publication in new window or tab >>Association between amygdala neurokinin-1 receptor availability and anxiety-related personality traits
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2018 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 8, no 1, p. 168-Article in journal (Refereed) Published
Abstract [en]

Animal studies indicate that substance P (SP) and its preferred neurokinin-1 (NK1) receptor modulate stress and anxiety-related behavior. Alterations in the SP-NK1 system have also been observed in human anxiety disorders, yet little is known about the relation between this system and individual differences in personality traits associated with anxiety propensity and approach-avoidance behavior, including trait anxiety, neuroticism, and extraversion. Exploring this relation could provide important insights into the neurobiological underpinnings of human anxiety and the etiology of anxiety disorders, as anxious traits are associated with increased susceptibility to develop psychopathological conditions. Here we examined the relationship between central NK1 receptor availability and self-rated measures of trait anxiety, neuroticism, and extraversion. The amygdala was chosen as the primary region of interest since this structure has been suggested to mediate the effect of the SP-NK1 system on anxiety. Anxious traits and NK1 receptor availability, determined with positron emission tomography and the radiotracer [11C]GR205171, were measured in 17 healthy individuals. Voxel-wise analyses showed a significant positive correlation between bilateral amygdala NK1 receptor availability and trait anxiety, and a trend in similar direction was observed for neuroticism. Conversely, extraversion was found to be negatively associated with amygdala NK1 receptor availability. Extraversion also correlated negatively with the NK1 measure in the cuneus/precuneus and fusiform gyrus according to exploratory whole-brain analyses. In conclusion, our findings indicate that amygdala NK1 receptor availability is associated with anxiety-related personality traits in healthy subjects, consistent with a modulatory role for the SP-NK1 system in human anxiety.

National Category
Pedagogy
Identifiers
urn:nbn:se:uu:diva-358759 (URN)10.1038/s41398-018-0163-1 (DOI)000443079700001 ()
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-12-10Bibliographically approved
Jonasson, M., Langaas, G., Appel, L., Danfors, T., Fazio, P., Lubberink, M. & Varrone, A. (2018). Blood Flow Dependence of Early [C-11]PE2I and [F-18]FE-PE2I PET SUVR Measurements Used In the Differential Diagnosis of Parkinsonian Disorders. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S303-S304
Open this publication in new window or tab >>Blood Flow Dependence of Early [C-11]PE2I and [F-18]FE-PE2I PET SUVR Measurements Used In the Differential Diagnosis of Parkinsonian Disorders
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S303-S304Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-372963 (URN)000449266202217 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Available from: 2019-01-21 Created: 2019-01-21 Last updated: 2019-01-21Bibliographically approved
Lubberink, M., Widström, C., Jonasson, M., Appel, L., Fällmar, D., Nyholm, D., . . . Danfors, T. (2018). Differential diagnosis of patients with parkinsonian syndrome using multilinear regression to disease-specific C-11-PE2I-PET templates and classification tree learning. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S409-S409
Open this publication in new window or tab >>Differential diagnosis of patients with parkinsonian syndrome using multilinear regression to disease-specific C-11-PE2I-PET templates and classification tree learning
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S409-S409Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-372967 (URN)000449266204001 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved
Chiotis, K., Saint-Aubert, L., Rodriguez-Vieitez, E., Leuzy, A., Almkvist, O., Savitcheva, I., . . . Nordberg, A. (2018). Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer's disease dementia. Molecular Psychiatry, 23(7), 1666-1673
Open this publication in new window or tab >>Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer's disease dementia
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2018 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 7, p. 1666-1673Article in journal (Refereed) Published
Abstract [en]

The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. All patients underwent PET scans with [(18)F]THK5317 (tau deposition) and [(18)F]FDG (glucose metabolism) at baseline and follow-up, neuropsychological assessment at baseline and follow-up and a scan with [(11)C]PIB (amyloid-β deposition) at baseline only. At a group level, patients with AD (prodromal or dementia) showed unchanged [(18)F]THK5317 retention over time, in contrast to significant decreases in [(18)F]FDG uptake in temporoparietal areas. The pattern of changes in [(18)F]THK5317 retention was heterogeneous across all patients, with qualitative differences both between the two AD groups (prodromal and dementia) and among individual patients. High [(18)F]THK5317 retention was significantly associated over time with low episodic memory encoding scores, while low [(18)F]FDG uptake was significantly associated over time with both low global cognition and episodic memory encoding scores. Both patients with corticobasal syndrome had a negative [(11)C]PIB scan, high [(18)F]THK5317 retention with a different regional distribution from that in AD, and a homogeneous pattern of increased [(18)F]THK5317 retention in the basal ganglia over time. These findings highlight the heterogeneous propagation of tau pathology among patients with symptomatic AD, in contrast to the homogeneous changes seen in glucose metabolism, which better tracked clinical progression.Molecular Psychiatry advance online publication, 16 May 2017; doi:10.1038/mp.2017.108.

National Category
Neurosciences Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-322909 (URN)10.1038/mp.2017.108 (DOI)000442358000015 ()28507319 (PubMedID)
Funder
Swedish Research Council, 05817Swedish Foundation for Strategic Research Stockholm County CouncilGun och Bertil Stohnes StiftelseThe Karolinska Institutet's Research FoundationThe Swedish Brain FoundationWenner-Gren FoundationsEU, FP7, Seventh Framework ProgrammeThe Dementia Association - The National Association for the Rights of the Demented
Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2018-11-05Bibliographically approved
Leuzy, A., Rodriguez-Vieitez, E., Saint-Aubert, L., Chiotis, K., Almkvist, O., Savitcheva, I., . . . Nordberg, A. (2018). Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease.. Alzheimer's & Dementia, 14(5), 652-663
Open this publication in new window or tab >>Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease.
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2018 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 5, p. 652-663Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Cross-sectional findings using the tau tracer [18F]THK5317 (THK5317) have shown that [18F]fluorodeoxyglucose (FDG) positron emission tomography data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single positron emission tomography study can provide both functional and molecular information.

METHODS: We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change.

RESULTS: Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317.

DISCUSSION: Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.

Keywords
Alzheimer's disease, Alzheimer's disease dementia, FDG, Hypometabolism, Longitudinal study, Mild cognitive impairment, Neurofibrillary tangles, Perfusion SUVR, Perfusion imaging, Positron emission tomography (PET), Prodromal Alzheimer's disease, R(1), THK5317, Tau imaging
National Category
Radiology, Nuclear Medicine and Medical Imaging Medicinal Chemistry Neurosciences
Identifiers
urn:nbn:se:uu:diva-337704 (URN)10.1016/j.jalz.2017.11.008 (DOI)000432438800009 ()29268078 (PubMedID)
Funder
Swedish Research Council, 05817Swedish Foundation for Strategic Research Gun och Bertil Stohnes StiftelseThe Karolinska Institutet's Research FoundationThe Swedish Brain FoundationWenner-Gren Foundations
Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-08-01Bibliographically approved
Jonasson, M. (2018). Towards Clinical Implementation of Dynamic Positron Emission Tomography in Neurodegenerative Diseases. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
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
Keywords
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
Jonasson, M., Appel, L., Danfors, T., Nyholm, D., Askmark, H., Frick, A., . . . Lubberink, M. (2017). Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.. American Journal of Nuclear Medicine and Molecular Imaging, 7(6), 263-274
Open this publication in new window or tab >>Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.
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2017 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 7, no 6, p. 263-274Article in journal (Refereed) Published
Abstract [en]

[11C]PE2I is a highly selective dopamine transporter PET ligand. Parametric images based on dynamic [11C]PE2I scans, showing dopamine transporter availability (BPND) and relative cerebral blood flow (R1), can be used in differential diagnosis of parkinsonism. This work aimed to investigate a shortened scan duration and automated generation of parametric images which are two prerequisites for routine clinical application. Twelve subjects with parkinsonism and seventeen healthy controls underwent 80 min dynamic [11C]PE2I PET scans. BPND and R1 images were generated using cerebellum reference region defined on a co-registered MRI, as well as a supervised cluster analysis (SVCA)-based reference. Initial 20, 30 and 40 min of the scans were extracted and images of standardized uptake value ratio (SUVR) and R1 were computed using MRI- and SVCA-based reference. Correlation was high between striatal 80 min MRI-based BPND and 40 min SVCA-based SUVR-1 (R2=0.95). High correlation was also found between R1 values in striatal and limbic regions (R2≥0.91) whereas correlation was moderate for cortical regions (R2=0.71). The results indicate that dynamic [11C]PE2I scans can be restricted to 40 min and that SVCA can be used for automatic extraction of a reference region. These outcomes will support routine applications of [11C]PE2I PET in clinical settings.

Keywords
PET, [11C]PE2I, parametric images, parkinsonism, supervised clustering
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-340790 (URN)000419593300003 ()29348981 (PubMedID)
Funder
Swedish Research CouncilSwedish Society for Medical Research (SSMF)
Available from: 2018-02-02 Created: 2018-02-02 Last updated: 2018-02-21Bibliographically approved
Heurling, K., Leuzy, A., Jonasson, M., Frick, A., Zimmer, E. R., Nordberg, A. & Lubberink, M. (2017). Quantitative positron emission tomography in brain research. Brain Research, 1670, 220-234, Article ID S0006-8993(17)30270-6.
Open this publication in new window or tab >>Quantitative positron emission tomography in brain research
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2017 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1670, p. 220-234, article id S0006-8993(17)30270-6Article, review/survey (Refereed) Published
Abstract [en]

The application of positron emission tomography (PET) in brain research has increased substantially during the past 20 years, and is still growing. PET provides a unique insight into physiological and pathological processes in vivo. In this article we introduce the fundamentals of PET, and the methods available for acquiring quantitative estimates of the parameters of interest. A short introduction to different areas of application is also given, including basic research of brain function and in neurology, psychiatry, drug receptor occupancy studies, and its application in diagnostics of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Our aim is to inform the unfamiliar reader of the underlying basics and potential applications of PET, hoping to inspire the reader into considering how the technique could be of benefit for his or her own research.

Keywords
Brain, Diagnostics, Imaging biomarkers, Molecular imaging, Positron emission tomography
National Category
Neurosciences Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-326069 (URN)10.1016/j.brainres.2017.06.022 (DOI)000407666000024 ()28652218 (PubMedID)
Available from: 2017-06-30 Created: 2017-06-30 Last updated: 2018-01-13Bibliographically approved
Jonasson, M., Comasco, E., Nordeman, P., Wilking, H., De Grauw, H., Takahashi, K., . . . Lubberink, M. (2017). Tracer kinetic analysis of [C-11] Cetrozole as a PET tracer for aromatase in the human brain. Paper presented at 28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, APR 01-04, 2017, Int Soc Cerebral Blood Flow & Metab, Berlin, Germany. Journal of Cerebral Blood Flow and Metabolism, 37, 71-72
Open this publication in new window or tab >>Tracer kinetic analysis of [C-11] Cetrozole as a PET tracer for aromatase in the human brain
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2017 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, p. 71-72Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SAGE PUBLICATIONS INC, 2017
National Category
Endocrinology and Diabetes Hematology Neurology
Identifiers
urn:nbn:se:uu:diva-331030 (URN)000400157400104 ()
Conference
28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, APR 01-04, 2017, Int Soc Cerebral Blood Flow & Metab, Berlin, Germany
Note

Supplement: 1, Meeting Abstract: BPS01-3

Available from: 2017-10-10 Created: 2017-10-10 Last updated: 2017-10-10
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