| 1. |
- Engler, Henry, et al.
(författare)
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Two-year follow-up of amyloid deposition in patients with Alzheimer's disease
- 2006
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 129:Pt 11, s. 2856-2866
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Tidskriftsartikel (refereegranskat)abstract
- Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 +/- 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) after 2.0 +/- 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-d-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test-retest). Relative PIB retention in cortical regions differed by 3-7% in the test-retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 +/- 3.7 (mean +/- standard deviation) to 22.7 +/- 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 +/- 3.5 to 15.6 +/- 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 +/- 3.1 to 25.9 +/- 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.
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| 2. |
- Forsberg, Anton, et al.
(författare)
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PET imaging of amyloid deposition in patients with mild cognitive impairment
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1456-1465
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Tidskriftsartikel (refereegranskat)abstract
- It is of great clinical value to identify subjects at a high risk of developing AD. We previously found that the amyloid positron emission tomography (PET) tracer PIB showed a robust difference in retention in the brain between AD patients and healthy controls (HC). Twenty-one patients diagnosed with MCI (mean age 63.3 ± 7.8 (S.D.) years) underwent PET studies with 11C-PIB, and 18F-fluoro-deoxy-glucose (FDG) to measure cerebral glucose metabolism, as well as assessment of cognitive function and CSF sampling. Reference group data from 27 AD patients and 6 healthy controls, respectively, were used for comparison. The mean cortical PIB retention for the MCI patients was intermediate compared to HC and AD. Seven MCI patients that later at clinical follow-up converted to AD (8.1 ± 6.0 (S.D.) months) showed significant higher PIB retention compared to non-converting MCI patients and HC, respectively (ps < 0.01). The PIB retention in MCI converters was comparable to AD patients (p > 0.01). Correlations were observed in the MCI patients between PIB retention and CSF Aβ1-42, total Tau and episodic memory, respectively.
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| 3. |
- Höglund, Johanna, et al.
(författare)
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F-18-ML-10, a PET Tracer for Apoptosis : First Human Study
- 2011
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 52:5, s. 720-725
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Tidskriftsartikel (refereegranskat)abstract
- Clinical PET of apoptosis may have substantial value in advancing patient care. We report here the first-in-humans study with F-18-labeled 2-(5-fluoropentyl)-2-methyl malonic acid (F-18-ML-10), a small-molecule PET tracer for apoptosis. Presented are the dosimetry, biodistribution, stability, and safety profiles of this PET tracer in healthy human volunteers. Also reported is tracer binding to targeted apoptotic cells in testicular tissue, where a relative abundance of apoptotic cells is normally observed. Methods: F-18-ML-10 (233 +/- 90 MBq) was intravenously administered to 8 healthy subjects, followed by whole-body PET/CT for 220 min. Serial blood and urine samples were collected for radioactivity measurement, and plasma tracer stability was assessed by high-performance liquid chromatography. Dosimetry calculations were performed using OLINDA/EXM software. Results: F-18-ML-10 manifested high stability in vivo and rapid distribution followed by fast clearance, with an elimination half-life of 1.3 +/- 0.1 and 1.1 +/- 0.2 h from the blood and from all other organs, respectively, and excretion through the urine. Dosimetry showed an average effective whole-body dose of 15.4 +/- 3.7 mu Sv/MBq, with the urinary bladder being the dose-limiting organ. Selective accumulation and retention of the tracer in the testes was observed in all male subjects, a finding also demonstrated in mice using both small-animal PET and histopathology, confirming binding to apoptotic cells. Administration of F-18-ML-10 was safe, without adverse effects. Conclusion: F-18-ML-10 administered to healthy humans demonstrated a favorable dosimetry, biodistribution, stability, and safety profile. Binding to apoptotic sites was also demonstrated. These data support further development of this small-molecule probe for clinical PET of apoptosis.
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| 4. |
- Razifar, Pasha, et al.
(författare)
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An automated method for delineating a reference region using masked volumewise principal-component analysis in 11C-PIB PET
- 2009
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Ingår i: Journal of Nuclear Medicine Technology. - : Society of Nuclear Medicine. - 0091-4916 .- 1535-5675. ; 37:1, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- Kinetic modeling using a reference region is a common method for the analysis of dynamic PET studies. Available methods for outlining regions of interest representing reference regions are usually time-consuming and difficult and tend to be subjective; therefore, MRI is used to help physicians and experts to define regions of interest with higher precision. The current work introduces a fast and automated method to delineate the reference region of images obtained from an N-methyl-(11)C-2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole ((11)C-PIB) PET study on Alzheimer disease patients and healthy controls using a newly introduced masked volumewise principal-component analysis.METHODS: The analysis was performed on PET studies from 22 Alzheimer disease patients (baseline, follow-up, and test/retest studies) and 4 healthy controls, that is, a total of 26 individual scans. The second principal-component images, which illustrate the kinetic behavior of the tracer in gray matter of the cerebellar cortex, were used as input data for automatic delineation of the reference region. To study the variation associated with the manual and proposed automatic methods, we defined the reference region repeatedly.RESULTS: As expected, the automatic method showed no variation whereas the manual method varied significantly on repetition. Furthermore, the automatic method was significantly faster, more robust, and less biased.CONCLUSION: The automatic method is helpful in the delineation of the reference region of (11)C-PIB PET studies of the human brain and is much faster and more precise than manual delineation.
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| 5. |
- Razifar, Pasha, et al.
(författare)
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Masked-Volume-Wise PCA and "reference Logan" illustrate similar regional differences in kinetic behavior in human brain PET study using [11C]-PIB
- 2009
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Kinetic modeling using reference Logan is commonly used to analyze data obtained from dynamic Positron Emission Tomography (PET) studies on patients with Alzheimer's disease (AD) and healthy volunteers (HVs) using amyloid imaging agent N-methyl [(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, [(11)C]-PIB. The aim of the present study was to explore whether results obtained using the newly introduced method, Masked Volume Wise Principal Component Analysis, MVW-PCA, were similar to the results obtained using reference Logan. Methods: MVW-PCA and reference Logan were performed on dynamic PET images obtained from four Alzheimer's disease (AD) patients on two occasions (baseline and follow-up) and on four healthy volunteers (HVs). Regions of interest (ROIs) of similar sizes were positioned in different parts of the brain in both AD patients and HVs where the difference between AD patients and HVs is largest. Signal-to-noise ratio (SNR) and discrimination power (DP) were calculated for images generated by the different methods and the results were compared both qualitatively and quantitatively. Results: MVW-PCA generated images that illustrated similar regional binding patterns compared to reference Logan images and with slightly higher quality, enhanced contrast, improved SNR and DP, without being based on modeling assumptions. MVW-PCA also generated additional MVW-PC images by using the whole dataset, which illustrated regions with different and uncorrelated kinetic behaviors of the administered tracer. This additional information might improve the understanding of kinetic behavior of the administered tracer. Conclusion: MVW-PCA is a potential multivariate method that without modeling assumptions generates high quality images, which illustrated similar regional changes compared to modeling methods such as reference Logan. In addition, MVW-PCA could be used as a new technique, applicable not only on dynamic human brain studies but also on dynamic cardiac studies when using PET.
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| 6. |
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| 7. |
- Razifar, Pasha, et al.
(författare)
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Principal component analysis with pre-normalization improves the signal-to-noise ratio and image quality in positron emission tomography studies of amyloid deposits in Alzheimer's disease
- 2009
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 54:11, s. 3595-3612
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Tidskriftsartikel (refereegranskat)abstract
- This study introduces a new approach for the application of principal component analysis (PCA) with pre-normalization on dynamic positron emission tomography (PET) images. These images are generated using the amyloid imaging agent N-methyl [C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([C-11]PIB) in patients with Alzheimer's disease (AD) and healthy volunteers (HVs). The aim was to introduce a method which, by using the whole dataset and without assuming a specific kinetic model, could generate images with improved signal-to-noise and detect, extract and illustrate changes in kinetic behavior between different regions in the brain. Eight AD patients and eight HVs from a previously published study with [C-11] PIB were used. The approach includes enhancement of brain regions where the kinetics of the radiotracer are different from what is seen in the reference region, pre-normalization for differences in noise levels and removal of negative values. This is followed by slice-wise application of PCA (SW-PCA) on the dynamic PET images. Results obtained using the new approach were compared with results obtained using reference Patlak and summed images. The new approach generated images with good quality in which cortical brain regions in AD patients showed high uptake, compared to cerebellum and white matter. Cortical structures in HVs showed low uptake as expected and in good agreement with data generated using kinetic modeling. The introduced approach generated images with enhanced contrast and improved signal-to-noise ratio (SNR) and discrimination power (DP) compared to summed images and parametric images. This method is expected to be an important clinical tool in the diagnosis and differential diagnosis of dementia.
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