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Imaging Studies of Olfaction in Health and Parkinsonism
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Olfactory loss is a common non-motor symptom of Parkinson’s disease (PD), often preceding the cardinal motor symptoms of the disease. The aim of this thesis was to: (a) evaluate whether olfactory examination can increase diagnostic accuracy, and (b) study the structural and functional neural basis of olfactory dysfunction in PD with different applications of Magnetic Resonance Imaging (MRI).

Paper I was a comparison of the diagnostic accuracy between a simple smell identification test and DaTSCAN Single Photon Emission Computerized Tomography (SPECT), a nuclear medicine tomographic imaging technique that is commonly used in patients with suspected parkinsonism. The results indicate that smell test is inferior to DaTSCAN SPECT, but the combination of these two methods can lead to improved diagnostic accuracy.

Paper II showed that diffusion MRI could detect discrete microstructural changes in the white matter of brain areas that participate in higher order olfactory neurotransmission, whereas MRI with Magnetization Transfer contrast could not.

Paper III was a methodological study on how two different acquisition parameters can affect the activation pattern of olfactory brain areas, as observed with functional MRI (fMRI). The results indicate that brief olfactory stimulation and fast sampling rate should be preferred on olfactory fMRI studies.

Paper IV used olfactory fMRI and resting-state fMRI in order to elucidate potentially altered activation patterns and functional connectivity within olfactory brain areas, between PD patients and healthy controls. Olfactory fMRI showed that olfactory impairment in PD is associated with significantly lower recruitment of the olfactory network. Resting-state fMRI did not detect any significant changes in the functional connectivity within the olfactory network of PD patients.

In conclusion, the included studies provide evidence of: (a) disease-related structural and functional changes in olfactory brain areas, and (b) beneficial addition of olfactory tests in the clinical work-up of patients with parkinsonism.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. , p. 72
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1661
National Category
Radiology, Nuclear Medicine and Medical Imaging Neurology Medical Laboratory and Measurements Technologies
Identifiers
URN: urn:nbn:se:liu:diva-154919DOI: 10.3384/diss.diva-154919ISBN: 9789176851357 (print)OAI: oai:DiVA.org:liu-154919DiVA, id: diva2:1293832
Public defence
2019-04-05, Granitsalen, Campus US, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2019-03-05 Created: 2019-03-05 Last updated: 2019-12-12Bibliographically approved
List of papers
1. The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes
Open this publication in new window or tab >>The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes
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2015 (English)In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 9, p. 2154-2163Article in journal (Refereed) Published
Abstract [en]

The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinsons disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand I-123-FP-CIT (DaTSCAN (R)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2015
Keywords
Parkinsons disease; Atypical parkinsonism; Parkinsonian syndromes; Olfaction; I-123-FP-CIT SPECT
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122669 (URN)10.1007/s00415-015-7830-4 (DOI)000363035400018 ()26122543 (PubMedID)
Note

Funding Agencies|Ostergotland County Council (ALF); Swedish Parkinsons Foundation

Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2019-03-05Bibliographically approved
2. Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging
Open this publication in new window or tab >>Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging
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2017 (English)In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed) Published
Abstract [en]

Background: Olfactory impairment is an early manifestation of Parkinsons disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter. Objective: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT. Methods: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions. Results: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls. Conclusions: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

Place, publisher, year, edition, pages
IOS PRESS, 2017
Keywords
Parkinson disease; smell; diffusion tensor imaging; magnetization transfer contrast imaging
National Category
Neurology
Identifiers
urn:nbn:se:liu:diva-138300 (URN)10.3233/JPD-161060 (DOI)000401801600010 ()28482644 (PubMedID)
Note

Funding Agencies|Swedish Parkinson Foundation; Linkoping University Hospital Research Fund; ALF Grants from Region Ostergotland

Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2019-03-05
3. Olfactory fMRI: Implications of Stimulation Length and Repetition Time
Open this publication in new window or tab >>Olfactory fMRI: Implications of Stimulation Length and Repetition Time
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2018 (English)In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed) Published
Abstract [en]

Studying olfaction with functional magnetic resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA), and by plotting the event-related time course of brain activation in the 4 olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all 4 olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
fMRI; olfaction; smell; repetition time
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-149862 (URN)10.1093/chemse/bjy025 (DOI)000438293600001 ()29726890 (PubMedID)
Note

Funding Agencies|Swedish Parkinson Foundation, Linkoping University Hospital Research Fund; ALF Grants from Region Ostergotland

Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2019-04-17

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