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Human brain function evaluated with rCBF-SPECT: memory and pain related changes and new diagnostic possibilities in Alzheimer’s disease
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this doctoral thesis was to study the influence of memory, pain, age and education on the regional cerebral blood flow (rCBF), i.e. brain function, in early Alzheimer's disease (AD) and in chronic neck pain patients in comparison to healthy controls and in healthy elderly per se. This was done by optimizing single photon emission computed tomography (SPECT) as a method to study rCBF with the tracer Technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and by matching all image data to a brain atlas before evaluation. The rCBF-SPECT was evaluated and developed to obtain higher diagnostic accuracy in AD and in chronic neck pain patients it was used to study basic pain related cerebral processes in chronic pain of different origin. A new semimanual registration method, based on fiducial marker, suitable for investigations with low spatial resolution was developed. The method was used to reconstruct images with an improved attenuation and scatter correction by using an attenuation-map calculated from the patients' previously acquired CT images.

The influence of age and education on rCBF was evaluated with statistical parametric mapping, SPM in healthy elderly. The main findings were age related changes in rCBF in regions close to interlobar and interhemispheric space but not in regions typically affected in early AD, except for the medial temporal lobe. The theory of a 'cognitive reserve' in individuals with a longer education was supported with findings in the lateral temporal lobe, a region related to semantic memory, and in the frontal lobe.

A cross-sectional study of chronic neck pain patients showed extensive rCBF changes in coping related regions in a non-traumatic pain patients compared to both healthy and a pain group with a traumatic origin, i.e. whiplash syndrome. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. This suggests different pain mechanisms in these groups.

The AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus. These changes were associated to episodic memory performance, and especially to face recognition. The diagnostic sensitivity for AD was high. The face recognition test (episodic memory) was used in AD patients to improve the sensitivity of method, i.e. memory-provoked rCBF-SPECT (MP-SPECT). The results were compared to healthy controls and the reductions of rCBF in temporoparietal regions were more pronounced in mild AD during provocation. Memory provocation increased the sensitivity of AD-related rCBF changes at group level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might then be of help to set diagnosis earlier.

In conclusion rCBF in temporoparietal regions are associated to an impaired episodic memory in early AD. Changes in these regions do not have a strong connection to chronological age. The diagnostic sensitivity of rCBF-SPECT in AD is high and there is a potentially higher sensitivity if memory provoked investigations are used. The findings in this thesis have given an increased knowledge of underlying cerebral pain processing in non-traumatic and traumatic (whiplash) neck pain. Preliminary results supporting the theory of 'cognitive reserve' by showing a correlation between long education and preserved rCBF was found in healthy elderly.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2006. , 74 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1016
Keyword [en]
brain imaging, rCBF, SPECT, early diagnosis, brain atlas, HMPAO, Alzheimer´s disease, Whiplash, neuropsychological function, episodic memory
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:umu:diva-761ISBN: 91-7264-051-0 (print)OAI: oai:DiVA.org:umu-761DiVA: diva2:144455
Public defence
2006-05-05, sal 260 röntgen, 3A 2tr, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2006-04-19 Created: 2006-04-19 Last updated: 2012-04-03Bibliographically approved
List of papers
1. A method for attenuation and scatter correction of brain SPECT based on computed tomography images
Open this publication in new window or tab >>A method for attenuation and scatter correction of brain SPECT based on computed tomography images
2003 (English)In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 24, no 4, 411-420 p.Article in journal (Refereed) Published
Abstract [en]

A method for attenuation and scatter correction of brain single photon emission computed tomography (SPECT) is described where computed tomography (CT) images of the brain are used for the calculation of attenuation maps. The method is evaluated for the substance 99mTc hexamethylpropylene amine oxime. A transmission dependent scatter correction is utilized and is based on ray sums calculated through the attenuation map. A method based on external markers is used to align the SPECT and CT image volumes. The markers need only to be present during the SPECT acquisition since the corresponding landmarks can be found without markers on the CT images. The mismatching has been investigated for five patients who have undergone both a CT examination and a SPECT examination with markers. Twelve individuals from the staff have pointed out the landmarks on the CT images, with an average standard deviation of 3.4 mm. Reconstructions with an attenuation map shifted the corresponding 95% confidence interval have been performed to obtain an estimation of the quantitative uncertainty caused by the mismatching, and quantitative errors of up to 6.3% have been measured. At present the method is probably most useful when groups of patients are studied.

Identifiers
urn:nbn:se:umu:diva-5081 (URN)10.1097/01.mnm.0000068299.89730.b4 (DOI)12673170 (PubMedID)
Available from: 2006-04-19 Created: 2006-04-19 Last updated: 2017-12-14Bibliographically approved
2. Influences of chronological age and length of education on rCBF-SPECT patternsin a healthy sample: Diagnostic implications
Open this publication in new window or tab >>Influences of chronological age and length of education on rCBF-SPECT patternsin a healthy sample: Diagnostic implications
Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-5082 (URN)
Available from: 2006-04-19 Created: 2006-04-19 Last updated: 2010-01-13Bibliographically approved
3. Altered cerebral blood flow in chronic neck pain patients but not in whiplash patients: a 99mTc-HMPAO rCBF study
Open this publication in new window or tab >>Altered cerebral blood flow in chronic neck pain patients but not in whiplash patients: a 99mTc-HMPAO rCBF study
Show others...
2006 (English)In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 15, no 8, 1189-1195 p.Article in journal (Refereed) Published
Abstract [en]

A cross-sectional study to investigate regional cerebral blood flow (rCBF) in patients with chronic whiplash syndrome and chronic neck pain patients without previous history of trauma along with a healthy control group. Chronic neck pain is a common disorder and a history of cervical spine injury including whiplash trauma constitute a risk factor for persistent neck pain. The aetiology of the late whiplash syndrome is unknown with no specific diagnostic criteria based on imaging, physiological, or psychological examination. Earlier studies indicate a parieto-occipital hypoperfusion but it is unclear if the hypoperfusion represents a response to chronic pain. The rCBF was monitored in 45 patients with chronic neck pain: 27 cases with chronic whiplash syndrome and 18 age and gender matched cases with non-traumatic chronic neck pain. The rCBF was estimated with single-photon emission computed tomography (SPECT) using technetium-99m hexamethylpropylene amine oxime (HMPAO). The non-traumatic patients displayed rCBF changes in comparison with the whiplash group and the healthy control group. These changes included rCBF decreases in a right temporal region close to hippocampus, and increased rCBF in left insula. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. The present study suggests different pain mechanisms in patients with chronic neck pain of non-traumatic origin compared to those with chronic neck pain due to a whiplash trauma.

Keyword
Adult, Chronic Disease, Female, Humans, Male, Middle Aged, Neck Pain/*pathology, Regional Blood Flow, Technetium Tc 99m Exametazime/diagnostic use, Telencephalon/*blood supply, Tomography; Emission-Computed; Single-Photon, Whiplash Injuries/*pathology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-12543 (URN)10.1007/s00586-005-0040-5 (DOI)16614854 (PubMedID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2017-12-14Bibliographically approved
4. Memory functions and rCBF (99m)Tc-HMPAO SPET: developing diagnostics in Alzheimer's disease
Open this publication in new window or tab >>Memory functions and rCBF (99m)Tc-HMPAO SPET: developing diagnostics in Alzheimer's disease
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2002 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, ISSN 1619-7070, Vol. 29, no 9, 1140-1148 p.Article in journal (Refereed) Published
Abstract [en]

Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age, with devastating consequences for the individual and society. The aim of this study was to evaluate whether patients with early AD show an altered regional cerebral blood flow (rCBF) compared with control persons. Furthermore, we aimed to investigate the correlation between rCBF in sublobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2+/-8.8 years) with early AD and 15 control persons (aged 71.4+/-3.2 years) were included. rCBF measurements with single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF (99m)Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and normalised for differences in rCBF (Computerised Brain Atlas software). Cortical and subcortical volumes of interest (VOIs) were analysed and compared. Compared with the controls, AD patients showed a significantly lower rCBF ratio in temporoparietal regions, including the left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared with age-matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions, including the left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD.

Identifiers
urn:nbn:se:umu:diva-5084 (URN)10.1007/s00259-002-0829-y (DOI)12192558 (PubMedID)
Available from: 2006-04-19 Created: 2006-04-19 Last updated: 2017-12-14Bibliographically approved
5. Memory-provoked rCBF-SPECT as a diagnostic tool in Alzheimer's disease?
Open this publication in new window or tab >>Memory-provoked rCBF-SPECT as a diagnostic tool in Alzheimer's disease?
Show others...
2006 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 33, no 1, 73-80 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Alzheimer's disease (AD) is a primary degenerative disease that progressively affects all brain functions, with devastating consequences for the patient, the patient's family and society. Rest regional cerebral blood flow (rCBF) could have a strategic role in differentiating between AD patients and normal controls, but its use for this purpose has a low discriminatory capacity. The purpose of this study was to evaluate whether the diagnostic sensitivity of rCBF single-photon emission computed tomography (SPECT) could be increased by using an episodic memory task provocation, i.e. memory-provoked rCBF-SPECT (MP-SPECT). METHODS: Eighteen persons (73.2+/-4.8 years) with mild AD and 18 healthy elderly (69.4+/-3.9 years) were included in the study. The subjects were injected with (99m)Tc-hexamethylpropylene amine oxime (HMPAO) during memory provocation with faces and names, followed by an rCBF-SPECT study. The rCBF (99m)Tc-HMPAO SPECT images were analysed using statistical parametric mapping (SPM2). Peaks with a false discovery rate corrected value of 0.05 were considered significant. RESULTS: On MP-SPECT, the AD group showed a significant rCBF reduction in the left parietal cortex in comparison with healthy elderly. At rest, no significant group differences were seen. CONCLUSION: Memory provocation increased the sensitivity of rCBF-SPECT for the detection of AD-related blood flow changes in the brain at the group level. Further studies are needed to evaluate MP-SPECT as a diagnostic tool at the individual level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might be sufficient in the clinical setting.

Identifiers
urn:nbn:se:umu:diva-13544 (URN)10.1007/s00259-005-1874-0 (DOI)16151770 (PubMedID)
Available from: 2007-02-27 Created: 2007-02-27 Last updated: 2017-12-14Bibliographically approved

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