| 1. |
- Heeman, F., et al.
(författare)
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Optimized dual-time-window protocols for quantitative F-18 flutemetamol and F-18 florbetaben PET studies
- 2019
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Ingår i: Ejnmmi Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA long dynamic scanning protocol may be required to accurately measure longitudinal changes in amyloid load. However, such a protocol results in a lower patient comfort and scanning efficiency compared to static scans. A compromise can be achieved by implementing dual-time-window protocols. This study aimed to optimize these protocols for quantitative [F-18]flutemetamol and [F-18]florbetaben studies.MethodsRate constants for subjects across the Alzheimer's disease spectrum (i.e., non-displaceable binding potential (BPND) in the range 0.02-0.77 and 0.02-1.04 for [F-18]flutemetamol and [F-18]florbetaben, respectively) were established based on clinical [F-18]flutemetamol (N=6) and [F-18]florbetaben (N=20) data, and used to simulate tissue time-activity curves (TACs) of 110min using a reference tissue and plasma input model. Next, noise was added (N=50) and data points corresponding to different intervals were removed from the TACs, ranging from 0 (i.e., 90-90=full-kinetic curve) to 80 (i.e., 10-90) minutes, creating a dual-time-window. Resulting TACs were fitted using the simplified reference tissue method (SRTM) to estimate the BPND, outliers (1.5xBP(ND) max) were removed and the bias was assessed using the distribution volume ratio (DVR=BPND+1). To this end, acceptability curves, which display the fraction of data below a certain bias threshold, were generated and the area under those curves were calculated.Results[F-18]Flutemetamol and [F-18]florbetaben data demonstrated an increased bias in amyloid estimate for larger intervals and higher noise levels. An acceptable bias (3.1%) in DVR could be obtained with all except the 10-90 and 20-90-min intervals. Furthermore, a reduced fraction of acceptable data and most outliers were present for these two largest intervals (maximum percentage outliers 48 and 32 for [F-18]flutemetamol and [F-18]florbetaben, respectively).ConclusionsThe length of the interval inversely correlates with the accuracy of the BPND estimates. Consequently, a dual-time-window protocol of 0-30 and 90-110min (=maximum of 60min interval) allows for accurate estimation of BPND values for both tracers.[F-18]flutemetamol: EudraCT 2007-000784-19, registered 8 February 2007, [F-18]florbetaben: EudraCT 2006-003882-15, registered 2006.
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| 2. |
- Landsverk, Ole J. B., et al.
(författare)
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Antibody-secreting plasma cells persist for decades in human intestine
- 2017
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Ingår i: Journal of Experimental Medicine. - NewYork, USA : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 214:2, s. 309-317
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Tidskriftsartikel (refereegranskat)abstract
- Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19(+) PC subset was dynamically exchanged, whereas of two CD19(-) PC subsets, CD45(+) PCs exhibited little and CD45(-) PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45(-) PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19(-) PC subsets support selection and maintenance of protective PCs for life in human intestine.
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| 3. |
- van der Doef, Thalia F, et al.
(författare)
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In vivo (R)-[(11)C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis.
- 2016
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Ingår i: NPJ schizophrenia. - : Springer Science and Business Media LLC. - 2334-265X. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[(11)C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease. (R)-[(11)C]PK11195 binding potential (BPND) was measured in 19 patients with recent onset psychosis and 17 age and gender-matched healthy controls. Total gray matter, as well as five gray matter regions of interest (frontal cortex, temporal cortex, parietal cortex, striatum, and thalamus) were defined a priori. PET data were analysed using a reference tissue approach and a supervised cluster analysis algorithm to identify the reference region. No significant difference in (R)-[(11)C]PK11195 BPND between patients and controls was found in total gray matter, nor one of the regions of interest. These findings suggest that microglia activation is not present in recent onset psychosis or that it is a subtle phenomenon that could not be detected using the design of the present study.
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| 4. |
- Wolters, Emma E., et al.
(författare)
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A novel partial volume correction method for accurate quantification of [18F] flortaucipir in the hippocampus
- 2018
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Off-target binding in the choroid plexus (CP) may cause spill-in of the tau PET tracer [18F] flortaucipir into the adjacent hippocampus region. The impact of this spill-in on hippocampal uptake was assessed using a novel partial volume correction method (PVC). Methods: PVC was performed on 20 [18F] flortaucipir dynamic PET scans (10 probable AD and 10 controls). Volumes of interest (VOIs) were defined for both hippocampus and CP. The correlation between hippocampal and CP distribution volume (VT), with and without PVC, was determined. Both anatomically defined and eroded VOIs were used. Results: For controls, the correlation between hippocampal and CP VT was significantly reduced after using PVC along with an eroded VOI (r2 = 0.59, slope = 0.80 versus r2 = 0.15, slope = 0.15; difference: p < 0.05). The same was true for AD patients (p < 0.05). Conclusion: PVC together with an optimized hippocampal VOI resulted in effective reduction of CP spill-in and improved accuracy of hippocampal VT.
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