| 1. |
- Westwood, S., et al.
(författare)
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Plasma Protein Biomarkers for the Prediction of CSF Amyloid and Tau and F-18 -Flutemetamol PET Scan Result
- 2018
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Blood biomarkers may aid in recruitment to clinical trials of Alzheimer's disease (AD) modifying therapeutics by triaging potential trials participants for amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) A beta and tau tests. Objective: To discover a plasma proteomic signature associated with CSF and PET measures of AD pathology. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics were performed in plasma from participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD, recruited to the Amsterdam Dementia Cohort, stratified by CSF Tau/A beta(42) (n = 50). Technical replication and independent validation were performed by immunoassay in plasma from SCD, MCI, and AD participants recruited to the Amsterdam Dementia Cohort with CSF measures (n = 100), MCI participants enrolled in the GE067-005 study with [F-18]-Flutemetamol PET amyloid measures (n = 173), and AD, MCI and cognitively healthy participants from the EMIF 500 study with CSF A beta(42) measurements (n = 494). Results: 25 discovery proteins were nominally associated with CSF Tau/A beta(42) (P < 0.05) with associations of ficolin-2 (FCN2), apolipoprotein C -IV and fibrinogen f, chain confirmed by immunoassay (P < 0.05). In the GE067-005 cohort, FCN2 was nominally associated with PET amyloid (P < 0.05) replicating the association with CSF Tau/A beta(42). There were nominally significant associations of complement component 3 with PET amyloid, and apolipoprotein(a), apolipoprotein A-I, ceruloplasmin, and PPY with MCI conversion to AD (all P < 0.05). In the EMIF 500 cohort FCN2 was trending toward a significant relationship with CSF A beta(42) (P approximate to 0.05), while both Al AT and clusterin were nominally significantly associated with CSF A beta(42) (both P < 0.05). Conclusion: Associations of plasma proteins with multiple measures of AD pathology and progression are demonstrated. To our knowledge this is the first study to report an association of FCN2 with AD pathology. Further testing of the proteins in larger independent cohorts will be important.
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| 2. |
- Zanette, I., et al.
(författare)
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Speckle-Based X-Ray Phase-Contrast and Dark-Field Imaging with a Laboratory Source
- 2014
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 112:25, s. 253903-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the observation and application of near-field speckles with a laboratory x-ray source. The detection of speckles is possible thanks to the enhanced brilliance properties of the used liquid-metal-jet source, and opens the way to a range of new applications in laboratory-based coherent x-ray imaging. Here, we use the speckle pattern for multimodal imaging of demonstrator objects. Moreover, we introduce algorithms for phase and dark-field imaging using speckle tracking, and we show that they yield superior results with respect to existing methods.
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| 3. |
- Zanette, I., et al.
(författare)
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X-ray microtomography using correlation of near-field speckles for material characterization
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:41, s. 12569-12573
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Tidskriftsartikel (refereegranskat)abstract
- Nondestructive microscale investigation of objects is an invaluable tool in life and materials sciences. Currently, such investigation is mainly performed with X-ray laboratory systems, which are based on absorption-contrast imaging and cannot access the information carried by the phase of the X-ray waves. The phase signal is, nevertheless, of great value in X-ray imaging as it is complementary to the absorption information and in general more sensitive to visualize features with small density differences. Synchrotron facilities, which deliver a beam of high brilliance and high coherence, provide the ideal condition to develop such advanced phase-sensitive methods, but their access is limited. Here we show how a small modification of a laboratory setup yields simultaneously quantitative and 3D absorption and phase images of the object. This single-shot method is based on correlation of X-ray near-field speckles and represents a significant broadening of the capabilities of laboratory- based X-ray tomography.
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| 4. |
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| 5. |
- Tapfer, A., et al.
(författare)
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Three-dimensional imaging of whole mouse models: comparing nondestructive X-ray phase-contrast micro-CT with cryotome-based planar epi-illumination imaging
- 2014
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720. ; 253:1, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we compare two evolving techniques for obtaining high-resolution 3D anatomical data of a mouse specimen. On the one hand, we investigate cryotome-based planar epi-illumination imaging (cryo-imaging). On the other hand, we examine X-ray phase-contrast micro-computed tomography (micro-CT) using synchrotron radiation. Cryo-imaging is a technique in which an electron multiplying charge coupled camera takes images of a cryo-frozen specimen during the sectioning process. Subsequent image alignment and virtual stacking result in volumetric data. X-ray phase-contrast imaging is based on the minute refraction of X-rays inside the specimen and features higher soft-tissue contrast than conventional, attenuation-based micro-CT. To explore the potential of both techniques for studying whole mouse disease models, one mouse specimen was imaged using both techniques. Obtained data are compared visually and quantitatively, specifically with regard to the visibility of fine anatomical details. Internal structure of the mouse specimen is visible in great detail with both techniques and the study shows in particular that soft-tissue contrast is strongly enhanced in the X-ray phase images compared to the attenuation-based images. This identifies phase-contrast micro-CT as a powerful tool for the study of small animal disease models.
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| 6. |
- Thal, D. R., et al.
(författare)
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Estimation of amyloid distribution by F-18 flutemetamol PET predicts the neuropathological phase of amyloid beta-protein deposition
- 2018
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 136:4, s. 557-567
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Tidskriftsartikel (refereegranskat)abstract
- The deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer’s disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging. To address this question we reassessed 97 cases of the end-of-life study cohort of the phase 3 [18F]flutemetamol trial (ClinicalTrials.gov identifiers NCT01165554, and NCT02090855) by combining the standardized uptake value ratios (SUVRs) with pons as reference region for cortical and caudate nucleus-related [18F]flutemetamol-retention. We tested them for their prediction of the neuropathological pattern found at autopsy. By defining threshold levels for cortical and caudate nucleus SUVRs we could distinguish different levels of [18F]flutemetamol uptake termed PET-Aβ phase estimates. When comparing these PET-Aβ phase estimates with the neuropathological Aβ-phases we found that PET-Aβ phase estimate 0 corresponded with Aβ-phases 0-2, 1 with Aβ-phase 3, 2 with Aβ-phase 4, and 3 with Aβ-phase 5. Classification using the PET-Aβ phase estimates predicted the correct Aβ-phase in 72.16% of the cases studied here. Bootstrap analysis was used to confirm the robustness of the estimates around this association. When allowing a range of±1 phase for a given Aβ-phase correct classification was given in 96.91% of the cases. In doing so, we provide a novel method to convert SUVR-levels into PET-Aβ phase estimates that can be easily translated into neuropathological phases of Aβ-deposition. This method allows direct conclusions about the pathological distribution of amyloid plaques (Aβ-phases) in vivo. Accordingly, this method may be ideally suited to detect early preclinical AD-patients, to follow them with disease progression, and to provide a more precise prognosis for them based on the knowledge about the underlying pathological phase of the disease.
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| 7. |
- Zhou, Tunhe, et al.
(författare)
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Noise analysis of speckle-based x-ray phase-contrast imaging
- 2016
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Ingår i: Optics Letters. - : The Optical Society. - 0146-9592 .- 1539-4794. ; 41:23, s. 5490-5493
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Tidskriftsartikel (refereegranskat)abstract
- Speckle-based x-ray phase-contrast imaging has drawn increasing interest in recent years as a simple, multimodal, cost-efficient, and laboratory-source adaptable method. We investigate its noise properties to help further optimization on the method and further comparison with other phase-contrast methods. An analytical model for assessing noise in a differential phase signal is adapted from studies on the digital image correlation technique in experimental mechanics and is supported by simulations and experiments. The model indicates that the noise of the differential phase signal from speckle-based imaging has a behavior similar to that of the grating-based method.
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| 8. |
- Zhou, Tunhe, et al.
(författare)
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Speckle-based x-ray phase-contrast imaging with a laboratory source and the scanning technique
- 2015
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Ingår i: Optics Letters. - : Optics Info Base, Optical Society of America. - 0146-9592 .- 1539-4794. ; 40:12, s. 2822-2825
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Tidskriftsartikel (refereegranskat)abstract
- The speckle-based scanning method for x-ray phase-contrast imaging is implemented with a liquid-metal-jet source. Using the two-dimensional scanning technique, the phase shift introduced by the object is retrieved in both transverse orientations, and the limitations on spatial resolution inherent to the speckle-tracking technique are avoided. This method opens up possibilities of new high-resolution multimodal applications for lab-based phasecontrast x-ray imaging.
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