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­­­Visual assessment of perfusion and metabolism in neurodegenerative dementia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. (Elna-Marie Larsson)ORCID iD: 0000-0001-5615-2036
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A worldwide demographic shift is currently occurring, with rapidly increasing numbers of elderly individuals. Since the incidence of neurodegenerative disease generally increases with age, this entails an increase in dementia prevalence. There are several strong incentives for establishing robust and widely available imaging methods for the early diagnosis of these diseases. Atrophy patterns are evident only late in the disease process, and the distinction from healthy ageing can often be elusive. For early diagnosis, physiologic parameters such as perfusion or metabolism must be assessed. The available modalities all have restricted clinical usefulness. The main aim of this thesis was to advance the clinical usefulness of perfusion and metabolism imaging in patients with neurodegenerative dementia, with a focus on visual assessment.

A cohort of patients with neurodegenerative dementia was included, along with an age-matched control group. All subjects underwent MRI, including a pseudocontinuous ASL sequence and FDG-PET. In papers II and III, a subgroup containing both patients and controls underwent a second FDG-PET with reduced dose. In paper IV, the material was combined with a similar cohort from Amsterdam.

Paper I showed that spatial smoothing increased the correlation between visually assessed perfusion and metabolism levels as displayed with FDG-PET. However, the distinction between patients and healthy controls was less satisfactory due to false positives.

Paper II showed that differences in regional standard uptake value ratios between normal- and low-dose FDG-PET were small and without clinically significant bias.

Paper III showed that the diagnostic performance of Z-score maps showing regions of significant deficits in metabolism was highly similar in normal- and low-dose FDG-PET images. 

Paper IV showed that ASL perfusion-based Z-score maps can be used for diagnostic purposes with high specificity, but inferior sensitivity, compared to FDG-PET.

In conclusion, the included studies address aspects of the visual assessment of perfusion and metabolism neuroimaging, with a focus on clinical usefulness in diagnosing neurodegenerative dementia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1266
Keyword [en]
Dementia, Neurodegenerative, Brain imaging, Diagnostics, Neuroradiology, Neuroimaging
Keyword [sv]
Demens, Neurodegenerativ, Hjärnavbildning, diagnostik, Neuroradiologi, Neuroimaging
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
URN: urn:nbn:se:uu:diva-304731ISBN: 978-91-554-9714-9OAI: oai:DiVA.org:uu-304731DiVA: diva2:1033714
Public defence
2016-12-07, Gunnesalen, Akademiska Sjukhuset, ing 10, 751 85, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2016-11-14 Created: 2016-10-08 Last updated: 2016-11-30
List of papers
1. Visual Assessment of Brain Perfusion MRI Scans in Dementia: a Pilot Study
Open this publication in new window or tab >>Visual Assessment of Brain Perfusion MRI Scans in Dementia: a Pilot Study
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2016 (English)In: Journal of Neuroimaging, ISSN 1051-2284, E-ISSN 1552-6569, Vol. 26, no 3, 324-330 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Functional imaging is becoming increasingly important for the detection of neurodegenerative disorders. Perfusion MRI with arterial spin labeling (ASL) has been reported to provide promising diagnostic possibilities but is not yet widely used in routine clinical work. The aim of this study was to compare, in a clinical setting, the visual assessment of subtracted ASL CBF maps with and without additional smoothing, to FDG-PET data.

METHODS: Ten patients with a clinical diagnosis of dementia and 11 age-matched cognitively healthy controls were examined with pseudo-continuous ASL (pCASL) and 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET). Three diagnostic physicians visually assessed the pCASL maps after subtraction only, and after postprocessing using Gaussian smoothing and GLM-based beta estimate functions. The assessment scores were compared to FDG PET values. Furthermore, the ability to discriminate patients from healthy elderly controls was assessed.

RESULTS: Smoothing improved the correlation between visually assessed regional ASL perfusion scores and the FDG PET SUV-r values from the corresponding regions. However, subtracted pCASL maps discriminated patients from healthy controls better than smoothed maps. Smoothing increased the number of false-positive patient identifications. Application of beta estimate functions had only a marginal effect.

CONCLUSION: Spatial smoothing of ASL images increased false positive results in the discrimination of hypoperfusion conditions from healthy elderly. It also decreased interreader agreement. However, regional characterization and subjective perception of image quality was improved.

Keyword
Arterial spin labeling; smoothing; visual assessment; brain perfusion; clinical setting
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-266305 (URN)10.1111/jon.12296 (DOI)000382869200012 ()26376736 (PubMedID)
Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2016-11-23Bibliographically approved
2. Validation of true low-dose 18F-FDG PET of the brain
Open this publication in new window or tab >>Validation of true low-dose 18F-FDG PET of the brain
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2016 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 6, no 5, 269-276 p.Article in journal (Refereed) Published
Abstract [en]

The dosage of 18F-FDG must be sufficient to ensure adequate PET image quality. For younger patients and research controls, the lowest possible radiation dose should be used. The purpose of this study was to find a protocol for FDG-PET of the brain with reduced radiation dose and preserved quantitative characteristics. Eight patients with neurodegenerative disorders and nine controls (n=17) underwent FDG-PET/CT twice on separate occasions, first with normal-dose (3 MBq/kg), and second with low-dose (0.75 MBq/kg, 25% of the original). Five additional controls (total n=22) underwent FDG-PET twice, using normal-dose and ultra-low-dose (0.3 MBq/kg, 10% of original). All subjects underwent MRI. Ten-minute summation images were spatially normalized and intensity normalized. Regional standard uptake value ratios (SUV-r) were calculated using an automated atlas. SUV-r values from the normal- and low-dose images were compared pairwise. No clinically significant bias was found in any of the three groups. The mean absolute difference in regional SUV-r values was 0.015 (1.32%) in controls and 0.019 (1.67%) in patients. The ultra-low-dose protocol produced a slightly higher mean difference of 0.023 (2.10%). The main conclusion is that 0.75 MBq/kg (56 MBq for a 75-kg subject) is a sufficient FDG dose for evaluating regional SUV-ratios in brain PET scans in adults with or without neurodegenerative disease, resulting in a reduction of total PET/CT effective dose from 4.54 to 1.15 mSv. The ultra-low-dose (0.5 mSv) could be useful in research studies requiring serial PET in healthy controls or children.

Place, publisher, year, edition, pages
Madison, USA: e-Century Publishing Corporation, 2016
Keyword
PET, FDG, neuroimaging, neurodegeneration, methodology, Hjärnavbildning, PET, lågdos, demens, neurodegenerativ
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-304730 (URN)
Available from: 2016-10-08 Created: 2016-10-08 Last updated: 2016-10-10Bibliographically approved
3. Reliable Z-score maps from low-dose 18F-FDG PET of the brain
Open this publication in new window or tab >>Reliable Z-score maps from low-dose 18F-FDG PET of the brain
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(English)Manuscript (preprint) (Other academic)
Keyword
Demens, Neurodegenerativ, Hjärnavbildning, Diagnostik
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-304727 (URN)
Available from: 2016-10-08 Created: 2016-10-08 Last updated: 2016-10-09
4. Arterial Spin Labeling versus FDG-PET for Differential Diagnosis in Dementia – use of Z-maps for visual assessment
Open this publication in new window or tab >>Arterial Spin Labeling versus FDG-PET for Differential Diagnosis in Dementia – use of Z-maps for visual assessment
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(English)Article in journal (Other academic) Submitted
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-304728 (URN)
Available from: 2016-10-08 Created: 2016-10-08 Last updated: 2016-10-09

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