| 1. |
- Ahmadi, Khazar, et al.
(författare)
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Fixel-Based Analysis Reveals Tau-Related White Matter Changes in Early Stages of Alzheimer’s Disease
- 2024
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Ingår i: Journal of Neuroscience. - 0270-6474. ; 44:18
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown white matter (WM) abnormalities in Alzheimer’s disease (AD) using diffusion tensor imaging (DTI). Nonetheless, robust characterization of WM changes has been challenging due to the methodological limitations of DTI. We applied fixel-based analyses (FBA) to examine microscopic differences in fiber density (FD) and macroscopic changes in fiber cross-section (FC) in early stages of AD (N = 393, 212 females). FBA was also compared with DTI, free-water corrected (FW)-DTI and diffusion kurtosis imaging (DKI). We further investigated the correlation of FBA and tensor-derived metrics with AD pathology and cognition. FBA metrics were decreased in the entire cingulum bundle, uncinate fasciculus and anterior thalamic radiations in Aβ-positive patients with mild cognitive impairment compared to control groups. Metrics derived from DKI, and FW-DTI showed similar alterations whereas WM degeneration detected by DTI was more widespread. Tau-PET uptake in medial temporal regions was only correlated with reduced FC mainly in the parahippocampal cingulum in Aβ-positive individuals. This tau-related WM alteration was also associated with impaired memory. Despite the spatially extensive between-group differences in DTI-metrics, the link between WM and tau aggregation was only revealed using FBA metrics implying high sensitivity but low specificity of DTI-based measures in identifying subtle tau-related WM degeneration. No relationship was found between amyloid load and any diffusion-MRI measures. Our results indicate that early tau-related WM alterations in AD are due to macrostructural changes specifically captured by FBA metrics. Thus, future studies assessing the effects of AD pathology in WM tracts should consider using FBA metrics.
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| 2. |
- Andersson, Emelie, et al.
(författare)
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Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer's disease
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 95, s. 143-153
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) neurofilament light (NfL) concentration has reproducibly been shown to reflect neurodegeneration in brain disorders, including Alzheimer's disease (AD). NfL concentration in blood correlates with the corresponding CSF levels, but few studies have directly compared the reliability of these 2 markers in sporadic AD. Herein, we measured plasma and CSF concentrations of NfL in 478 cognitively unimpaired (CU) subjects, 227 patients with mild cognitive impairment, and 113 patients with AD dementia. We found that the concentration of NfL in CSF, but not in plasma, was increased in response to Aβ pathology in CU subjects. Both CSF and plasma NfL concentrations were increased in patients with mild cognitive impairment and AD dementia. Furthermore, only NfL in CSF was associated with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF NfL increased before serum NfL in response to the development of Aβ pathology. In conclusion, NfL in CSF may be a more reliable biomarker of neurodegeneration than NfL in blood in preclinical sporadic AD.
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| 3. |
- Hahn, Andreas, et al.
(författare)
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Association Between Earliest Amyloid Uptake and Functional Connectivity in Cognitively Unimpaired Elderly
- 2019
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 29, s. 2173-2182
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in cognitive performance have been noted in nondemented subjects with elevated accumulation of amyloid-β (Aβ) fibrils. However, it is not yet understood whether brain function is already influenced by Aβ deposition during the very earliest stages of the disease. We therefore investigated associations between [18F]Flutemetamol PET, resting-state functional connectivity, gray and white matter structure and cognitive performance in 133 cognitively normal elderly that exhibited normal global Aβ PET levels. [18F]Flutemetamol uptake in regions known to accumulate Aβ fibrils early in preclinical AD (i.e., mainly certain parts of the default-mode network) was positively associated with dynamic but not static functional connectivity (r = 0.77). Dynamic functional connectivity was further related to better cognitive performance (r = 0.21-0.72). No significant associations were found for Aβ uptake with gray matter volume or white matter diffusivity. The findings demonstrate that the earliest accumulation of Aβ fibrils is associated with increased functional connectivity, which occurs before any structural alterations. The enhanced functional connectivity may reflect a compensatory mechanism to maintain high cognitive performance in the presence of increasing amyloid accumulation during the earliest phases of AD.
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| 4. |
- Hansson, Boel, et al.
(författare)
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Short-term effects experienced during examinations in an actively shielded 7T MR.
- 2019
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Ingår i: Bioelectromagnetics. - : Wiley. - 1521-186X .- 0197-8462. ; 40:4, s. 234-249
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate occurrence and strength of short-term effects experienced by study participants in an actively shielded (AS) 7 tesla (7T) magnetic resonance (MR) scanner, to compare results with earlier reports on passively shielded (PS) 7T MR scanners, and to outline possible healthcare strategies to improve patient compliance. Study participants (n=124) completed a web-based questionnaire directly after being examined in an AS 7T MR (n=154 examinations). Most frequently experienced short-term effects were dizziness (84%) and inconsistent movement (70%), especially while moving into or out of the magnet. Peripheral nerve stimulation (PNS)-twitching-was experienced in 67% of research examinations and showed a dependence between strength of twitches and recorded predicted PNS values. Of the participants, 74% experienced noise levels as acceptable and the majority experienced body and room temperature as comfortable. Of the study participants, 95% felt well-informed and felt they had had good contact with the staff before the examination. Willingness to undergo a future 7T examination was high (>90%). Our study concludes short-term effects are often experienced during examinations in an AS 7T MR, leaving room for improvement in nursing care strategies to increase patient compliance. Bioelectromagnetics. 2019;9999:XX-XX. © 2019 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.
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| 5. |
- Hansson, Boel, et al.
(författare)
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Subjectively Reported Effects Experienced in an Actively Shielded 7T MRI: A Large-Scale Study.
- 2020
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Ingår i: Journal of magnetic resonance imaging : JMRI. - : Wiley. - 1522-2586 .- 1053-1807. ; 52:4, s. 1265-1276
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Tidskriftsartikel (refereegranskat)abstract
- Ultrahigh-field (UHF) MRI advances towards clinical use. Patient compliance is generally high, but few large-scale studies have investigated the effects experienced in 7T MRI systems, especially considering peripheral nerve stimulation (PNS) and caregiving.To evaluate the quantity, the intensity, and subjective experiences from short-term effects, focusing on the levels of comfort and compliance of subjects.Prospective.In all, 954 consecutive MRIs in 801 subjects for 3years.7T.After the 7T examination, a questionnaire was used to collect data.Descriptive statistics, Spearman's rank correlation, Mann-Whitney U-test, and t-test.The majority (63%) of subjects agreed that the MRI experience was comfortable and 93% would be willing to undergo future 7T MRI as a patient (5% undecided) and 82% for research purposes (12% undecided). The most common short-term effects experienced were dizziness (81%), inconsistent movement (68%), PNS (63%), headache (40%), nausea (32%), metallic taste (12%), and light flashes (8%). Of the subjects who reported having PNS (n = 603), 44% experienced PNS as "not uncomfortable at all," 45% as "little or very little uncomfortable," and 11% as "moderate to very much uncomfortable." Scanner room temperature was experienced more comfortable before (78%) than during (58%) examinations, and the noise level was acceptable by 90% of subjects. Anxiety before the examination was reported by 43%. Patients differed from healthy volunteers regarding an experience of headache, metallic taste, dizziness, or anxiety. Room for improvement was pointed out after 117 examinations concerning given information (n = 73), communication and sound system (n = 35), or nursing care (n = 15).Subjectively reported effects occur in actively shielded 7T MRI and include physiological responses and individual psychological issues. Although leaving room for improvement, few subjects experienced these effects being so uncomfortable that they would lead to aversion to future UHF examinations.1 TECHNICAL EFFICACY: Stage 5.
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| 6. |
- Harper, Luke, et al.
(författare)
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Structural and functional connectivity associations with anterior cingulate sulcal variability
- 2024
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Ingår i: Brain Structure and Function. - 1863-2653. ; 229:7, s. 1561-1576
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Tidskriftsartikel (refereegranskat)abstract
- Sulcation of the anterior cingulate may be defined by presence of a paracingulate sulcus, a tertiary sulcus developing during the third gestational trimester with implications on cognitive function and disease. In this cross-sectional study we examine task-free resting state functional connectivity and diffusion-weighted tract segmentation data from a cohort of healthy adults (< 60-year-old, n = 129), exploring the impact of ipsilateral paracingulate sulcal presence on structural and functional connectivity. Presence of a left paracingulate sulcus was associated with reduced fractional anisotropy in the left cingulum bundle and the left peri-genual and dorsal bundle segments, suggesting reduced structural organisational coherence in these tracts. This association was not observed in the offsite temporal cingulum bundle segment. Left paracingulate sulcal presence was associated with increased left peri-genual radial diffusivity and tract volume possibly suggesting increased U-fibre density in this region. Greater network dispersity was identified in individuals with an absent left paracingulate sulcus by presence of a significant, predominantly intraregional, frontal component of resting state functional connectivity which was not present in individuals with a present left paracingulate sulcus. Seed-based functional connectivity in pre-defined networks was not associated with paracingulate sulcal presence. These results identify a novel association between sulcation and structural connectivity in a healthy adult population with implications for conditions where this variation is of interest. Presence of a left paracingulate sulcus appears to alter local structural and functional connectivity, possibly as a result of the presence of a local network reliant on short association fibres.
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| 7. |
- Lampinen, Björn, et al.
(författare)
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Searching for the neurite density with diffusion MRI : Challenges for biophysical modeling
- 2019
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 40:8, s. 2529-2545
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Tidskriftsartikel (refereegranskat)abstract
- In vivo mapping of the neurite density with diffusion MRI (dMRI) is a high but challenging aim. First, it is unknown whether all neurites exhibit completely anisotropic (“stick-like”) diffusion. Second, the “density” of tissue components may be confounded by non-diffusion properties such as T2 relaxation. Third, the domain of validity for the estimated parameters to serve as indices of neurite density is incompletely explored. We investigated these challenges by acquiring data with “b-tensor encoding” and multiple echo times in brain regions with low orientation coherence and in white matter lesions. Results showed that microscopic anisotropy from b-tensor data is associated with myelinated axons but not with dendrites. Furthermore, b-tensor data together with data acquired for multiple echo times showed that unbiased density estimates in white matter lesions require data-driven estimates of compartment-specific T2 values. Finally, the “stick” fractions of different biophysical models could generally not serve as neurite density indices across the healthy brain and white matter lesions, where outcomes of comparisons depended on the choice of constraints. In particular, constraining compartment-specific T2 values was ambiguous in the healthy brain and had a large impact on estimated values. In summary, estimating neurite density generally requires accounting for different diffusion and/or T2 properties between axons and dendrites. Constrained “index” parameters could be valid within limited domains that should be delineated by future studies.
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| 8. |
- Lampinen, Björn, et al.
(författare)
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Towards unconstrained compartment modeling in white matter using diffusion-relaxation MRI with tensor-valued diffusion encoding
- 2020
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 84:3, s. 1605-1623
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To optimize diffusion-relaxation MRI with tensor-valued diffusion encoding for precise estimation of compartment-specific fractions, diffusivities, and T2 values within a two-compartment model of white matter, and to explore the approach in vivo. Methods: Sampling protocols featuring different b-values (b), b-tensor shapes (bΔ), and echo times (TE) were optimized using Cramér-Rao lower bounds (CRLB). Whole-brain data were acquired in children, adults, and elderly with white matter lesions. Compartment fractions, diffusivities, and T2 values were estimated in a model featuring two microstructural compartments represented by a “stick” and a “zeppelin.”. Results: Precise parameter estimates were enabled by sampling protocols featuring seven or more “shells” with unique b/bΔ/TE-combinations. Acquisition times were approximately 15 minutes. In white matter of adults, the “stick” compartment had a fraction of approximately 0.5 and, compared with the “zeppelin” compartment, featured lower isotropic diffusivities (0.6 vs. 1.3 μm2/ms) but higher T2 values (85 vs. 65 ms). Children featured lower “stick” fractions (0.4). White matter lesions exhibited high “zeppelin” isotropic diffusivities (1.7 μm2/ms) and T2 values (150 ms). Conclusions: Diffusion-relaxation MRI with tensor-valued diffusion encoding expands the set of microstructure parameters that can be precisely estimated and therefore increases their specificity to biological quantities.
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| 9. |
- Mannfolk, Peter, et al.
(författare)
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Can resting-state functional MRI serve as a complement to task-based mapping of sensorimotor function? A test-retest reliability study in healthy volunteers.
- 2011
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1522-2586 .- 1053-1807. ; 34, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate if resting-state functional MRI (fMRI) reliably can serve as a complement to task-based fMRI for presurgical mapping of the sensorimotor cortex. MATERIALS AND METHODS: Functional data were obtained in 10 healthy volunteers using a 3 Tesla MRI system. Each subject performed five bilateral finger tapping experiments interleaved with five resting-state experiments. Following preprocessing, data from eight volunteers were further analyzed with the general linear model (finger tapping data) and independent component analysis (rest data). Test-retest reliability estimates (hit rate and false alarm rate) for resting-state fMRI activation of the sensorimotor network were compared with the reliability estimates for task-evoked activation of the sensorimotor cortex. The reliability estimates constituted a receiver operating characteristics curve from which the area under the curve (AUC) was calculated. Statistical testing was performed to compare the two groups with respect to reliability. RESULTS: The AUC was generally higher for the task experiments, although median AUC was not significantly different on a group level. Also, the two groups showed comparable levels of within-group variance. CONCLUSION: Test-retest reliability was comparable between resting-state measurements and task-based fMRI, suggesting that presurgical mapping of functional networks can be a supplement to task-based fMRI in cases where patient status excludes task-based fMRI. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.
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| 10. |
- Mattsson, Niklas, et al.
(författare)
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Effects of APOE ε4 on neuroimaging, cerebrospinal fluid biomarkers, and cognition in prodromal Alzheimer's disease
- 2018
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 71, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure. Despite having similar cortical Aβ-load and baseline global cognition (mini mental state examination), APOE ε4-negative prodromal AD had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of Aβ-peptides and neuronal injury biomarkers, more white matter pathology, more cortical atrophy, and faster decline of mini mental state examination, compared to APOE ε4-positive prodromal AD. The absence of APOE ε4 is associated with an atypical phenotype of prodromal AD. This suggests that APOE ε4 may impact both the diagnostics of AD in early stages and potentially also effects of disease-modifying treatments.
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