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Nuclear medicine methods in idiopathic Parkinsonism: pre- and postsynaptic dopamine SPECT
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Nuklearmedicinska metoder vid idiopatisk Parkinsonism : pre- och postsynaptisk dopamin SPECT (Swedish)
Abstract [en]

Background: Single photon emission computed tomography (SPECT) with dopamine transporter (DAT) and dopamine D2 receptor (D2R) ligands can visualise the integrity of the nigrostriatal dopamine system. Parkinson’s disease (PD) and the atypical parkinsonian diseases (APD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), have similar symptoms and dopamine depletion, but differ in pharmacological response and prognosis. Clinical differentiation between PD and APD is often difficult in the early stages. The aims of the thesis were to evaluate the differential diagnostic and prognostic value of SPECT in early PD, MSA and PSP, to map the pattern of progression with dopamine SPECT, and map the pattern of dopamine SPECT in non-affected elderly volunteers with a prospective approach. Also, we evaluated the methodological aspects of dopamine SPECT with respect to image evaluation tools, reconstruction parameters and gamma cameras.

Methods: 172 patients, included in an on-going clinical prospective study on idiopathic parkinsonism, participated in the SPECT study. Also, 31 age-matched healthy controls (HC) were followed within this study. SPECT was done with 123I-FP-Cit (DAT SPECT) and 123I-IBZM (D2R SPECT). Regions of interest (ROI) were used as a standard method for semi-quantitative image analysis.

Results: SPECT uptake ratios from different gamma cameras could be equalised through correction equations derived from images of a brain-like phantom, provided that attenuation correction was applied. The ROI method had high reproducibility. SPECT uptake  in HC, measured with the ROI method and a volume based (VOI) method rendered similar trends, but gender and age differences in SPECT uptake were more marked with the VOI method, and less pronounced in DAT SPECT compared to D2R SPECT with both methods. The DAT SPECT uptake was significantly reduced in very early disease stage of PD and APD compared to HC. DATSPECT uptake was more reduced in PD with postural and gait disturbance (PIGD) compared to tremor-dominant PD. Decline in DAT SPECT uptake during the first year was more pronounced in PD and PSP compared to HC. D2R SPECT uptake overlapped between untreated PD and APD. After initiated treatment, the D2R SPECT uptake was significantly higher in MSA patients compared to PD, PSP and HC. Decline in D2R SPECT uptake during the first year was not significantly different between patients or compared to HC.

Conclusions: 123I-FP-Cit SPECT is a valuable and sensitive method to detect early stage idiopathic parkinsonism. A different level of uptake between PIGD-PD compared to TD-PD indicates a prognostic potential. It is not possible to differ between PD, MSA and PSP in early stage with 123I-FP-Cit SPECT and no differential diagnostic value was found using 123I-IBZM SPECT in the early, untreated stage of PD, MSA and PSP. A different pattern of uptake of this ligand in MSA compared to PD and PSP during the first years of L-dopa treatment may, however, indicate a diagnostic value during the follow-up period.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2013. , 69 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1550
Keyword [en]
Nuclear medicine, SPECT, 123I-FP-Cit, 123I-IBZM, dopamine, parkinsonism, Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
URN: urn:nbn:se:umu:diva-70275ISBN: 978-91-7459-557-4 (print)ISBN: 978-91-7459-646-5 (print)OAI: oai:DiVA.org:umu-70275DiVA: diva2:620930
Public defence
2013-06-05, Sal 206, byggnad 3A, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-05-15 Created: 2013-05-12 Last updated: 2013-05-15Bibliographically approved
List of papers
1. Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study
Open this publication in new window or tab >>Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study
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2010 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 37, no 11, 2154-2164 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The aim of this study was to assess the diagnostic contribution of pre- and postsynaptic dopamine SPECT in drug-naïve patients with early idiopathic parkinsonism and to investigate possible differences between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and possible differences in motor subtypes of parkinsonism.

METHODS: A group of 128 newly diagnosed idiopathic parkinsonian patients and 48 healthy controls was studied. Presynaptic baseline SPECT with (123)I-FP-CIT was performed in all patients and in 120 patients also a baseline postsynaptic SPECT with (123)I-IBZM. Clinical diagnoses were reassessed after 12 months.

RESULTS: Presynaptic uptake in the putamen and caudate was significantly reduced in patients compared to controls. Presynaptic uptake ratios were not different between PD patients and patients with APS, and postsynaptic uptake in APS was not significantly reduced compared to PD or controls. In half of the APS patients both pre- and postsynaptic uptake ratios were reduced on the same side in the striatum. Impaired motor performance was associated with decreased presynaptic uptake in the putamen in PD. The postural instability and gait difficulty (PIGD) subtype of PD had lower presynaptic uptake ratios than patients with tremor-dominated (TD) symptoms.

CONCLUSION: Not only presynaptic putamen uptake ratios, but also caudate ratios were reduced in a majority of the patients in our study. At baseline scan, i.e. in an early stage of the disease, the accuracy of excluding APS in the whole study population was 85% using a combination of pre- and postsynaptic SPECT. Already at baseline, lower presynaptic SPECT ratios were seen in PD with PIGD at onset compared to those with TD subtype.

Keyword
Parkinson’s disease, Parkinsonian syndromes, 123I-IBZM, 123I-FP-CIT, SPECT
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:umu:diva-36641 (URN)10.1007/s00259-010-1520-3 (DOI)000282424400018 ()20593284 (PubMedID)
Available from: 2010-10-06 Created: 2010-10-06 Last updated: 2013-05-15Bibliographically approved
2. Cross-camera comparison of ROI-based semi-quantitative 123I-IBZM SPECT data in healthy volunteers using an anthropomorphic phantom for calibration
Open this publication in new window or tab >>Cross-camera comparison of ROI-based semi-quantitative 123I-IBZM SPECT data in healthy volunteers using an anthropomorphic phantom for calibration
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2013 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 54, no 5, 549-556 p.Article in journal (Refereed) Published
Abstract [en]

Background In (123)I-Iolopride (IBZM) SPECT reference values may diverge between camera systems. If multicenter pooling of normal material databases is needed, differences in measured semi-quantitative data due to equipment performance and reconstruction parameters have to be investigated in each instance to determine the comparability.

Purpose To explore the differences in (123)I-IBZM measured uptake ratios between two different gamma cameras in healthy controls, the intra-rater reproducibility of the image evaluation method and the possibility to equalize uptake ratios by calibration through an anthropomorphic phantom.

Material and Methods Differences in ROI-based semi-quantitative data from two different gamma camera systems, the three-headed brain dedicated Neurocam and the two-headed multipurpose hybrid system Infinia Hawkeye, were studied using image data from a group of healthy volunteers and an anthropomorphic brain-phantom scanned with both cameras. Several reconstruction methods and corrections were applied. To test the reliability of the ROI method, the intra-observer reproducibility was determined for the ROI method in this study.

Results The ROI method had a high reliability. Differences in mean measured uptake (123)I-IBZM ratios in healthy controls varied between 2.9% and 6.5% depending on reconstruction and correction for attenuation and scatter. After calibration, the differences decreased. There were no statistically significant differences between corrected ratios from the two camera systems in the study when images were reconstructed with attenuation correction.

Conclusion The conformity of uptake ratios in attenuation corrected (123)I-IBZM images derived from the two different cameras was improved by using an anthropomorphic phantom for calibration.

Keyword
SPECT, IBZM, radionuclide imaging, imaging phantom, Parkinsonian Disorders, healthy volunteers
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:umu:diva-68836 (URN)10.1177/0284185113477392 (DOI)000322323400015 ()23463862 (PubMedID)
Available from: 2013-04-25 Created: 2013-04-25 Last updated: 2017-12-06Bibliographically approved
3. 123I-FP-Cit and 123I-IBZM SPECT uptake in a prospective normal material analysed with two different semi-quantitative image evaluation tools
Open this publication in new window or tab >>123I-FP-Cit and 123I-IBZM SPECT uptake in a prospective normal material analysed with two different semi-quantitative image evaluation tools
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2013 (English)In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 34, no 10, 978-989 p.Article in journal (Refereed) Published
Abstract [en]

Objective: The need for age-adjusted and/or sex-adjusted reference values in dopamine transporter (DAT) and dopamine D2 receptor (D2R) imaging with single-photon emission computed tomography (SPECT) in a longitudinal study of parkinsonian diseases was investigated. We used two different image evaluation tools with a cross-sectional and longitudinal statistical approach.

Materials and methods: Baseline DAT and/or D2R SPECT were performed in 51 healthy controls (HC), age-matched to patients in an ongoing prospective study on idiopathic parkinsonism. Twenty-four HC were re-examined after 3 years and 21 HC were examined again after 5 years. SPECT was performed with I-123-FP-Cit and I-123-IBZM on a two-headed hybrid gamma camera. Regions of interest and volumes of interest (VOIs) were used for image evaluation. A cross-sectional and longitudinal statistical analysis was carried out.

Results: Fewer sex-based differences and less age dependency were seen in DAT SPECT uptake ratios compared with D2R SPECT uptake ratios and when comparing uptake ratios obtained with regions of interest against those with VOIs. In the cross-sectional analysis, a significant age-dependent decline was seen in women in both DAT and D2R uptakes with the VOI method but not in men with either evaluation method. In the longitudinal dataset, both a slight decline and increase over time were seen in DAT uptake; however, a general pattern of decrease was seen in both men and women in D2R uptake.

Conclusion: The choice of the image evaluation method can influence the pattern of sex-based and age-related differences. The results speak for the use of age-stratified reference values for women, in particular when using a VOI method.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2013
Keyword
123I-FP-CIT, 123I-IBZM, ageing, dopamine, sex, prospective, single-photon emission computed tomography
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:umu:diva-70273 (URN)10.1097/MNM.0b013e328364aa2e (DOI)
Projects
NYPUMPROSPUM
Note

Originally published in thesis in manuscript form

Available from: 2013-05-12 Created: 2013-05-12 Last updated: 2017-12-06Bibliographically approved
4. Pre- and postsynaptic dopamine SPECT in idiopathic parkinsonian diseases: a follow-up study
Open this publication in new window or tab >>Pre- and postsynaptic dopamine SPECT in idiopathic parkinsonian diseases: a follow-up study
Show others...
2013 (English)In: BioMed Research International, ISSN 2314-6141, Vol. 2013, 143532- p.Article in journal (Refereed) Published
Abstract [en]

We prospectively evaluated the diagnostic contribution of 123I-FP-Cit (DAT) and 123I-IBZM (IBZM) SPECT in 29 patients with Parkinson’s disease (PD) (74.4 ± 4.2 years) and 28 patients with atypical parkinsonian diseases (APD) (74.3 ± 9.2 years). Twelve had multiple system atrophy (MSA) and 16 progressive supranuclear palsy (PSP). Sixteen age-matched healthy controls (HC) were included. DAT and IBZM SPECTs were made at baseline and after 1 year in all PD patients and in 20 (DAT) and 18 (IBZM) of the APD patients, and after 3 years in 22 (DAT) and 17 (IBZM) of the PD patients and in 10 (DAT) and 10 (IBZM) of the APD patients. The relative DAT uptake decrease was faster in PD and PSP than in HC and MSA. In PSP the DAT uptake was lower than in MSA after 1 year but not after 3 years. Baseline IBZM uptake was not significantly different between patients and HC or between PD and APD. One year after initiated dopaminergic treatment the mean IBZM uptake in the MSA patients remained high compared to PSP and after 3 years compared to PD, PSP, and HC.Thus, the pattern of uptake of these ligands over time may be of value in discriminating between these diagnoses.

Keyword
Parkinson’s disease, Multiple System Atrophy, Progressive Supranuclear Palsy, SPECT, 123I-FP-Cit, 123I-IBZM, prospective study
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:umu:diva-70274 (URN)10.1155/2013/143532 (DOI)000324939000001 ()24163811 (PubMedID)
Projects
NYPUMPROSPUM
Note

Originally published in thesis in manuscript form

Available from: 2013-05-12 Created: 2013-05-12 Last updated: 2013-11-21Bibliographically approved

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