| 1. |
- Lampinen, Björn, et al.
(författare)
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Neurite density imaging versus imaging of microscopic anisotropy in diffusion MRI : A model comparison using spherical tensor encoding
- 2017
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Ingår i: NeuroImage. - : Elsevier BV. - 1095-9572 .- 1053-8119. ; 147, s. 517-531
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Tidskriftsartikel (refereegranskat)abstract
- In diffusion MRI (dMRI), microscopic diffusion anisotropy can be obscured by orientation dispersion. Separation of these properties is of high importance, since it could allow dMRI to non-invasively probe elongated structures such as neurites (axons and dendrites). However, conventional dMRI, based on single diffusion encoding (SDE), entangles microscopic anisotropy and orientation dispersion with intra-voxel variance in isotropic diffusivity. SDE-based methods for estimating microscopic anisotropy, such as the neurite orientation dispersion and density imaging (NODDI) method, must thus rely on model assumptions to disentangle these features. An alternative approach is to directly quantify microscopic anisotropy by the use of variable shape of the b-tensor. Along those lines, we here present the 'constrained diffusional variance decomposition' (CODIVIDE) method, which jointly analyzes data acquired with diffusion encoding applied in a single direction at a time (linear tensor encoding, LTE) and in all directions (spherical tensor encoding, STE). We then contrast the two approaches by comparing neurite density estimated using NODDI with microscopic anisotropy estimated using CODIVIDE. Data were acquired in healthy volunteers and in glioma patients. NODDI and CODIVIDE differed the most in gray matter and in gliomas, where NODDI detected a neurite fraction higher than expected from the level of microscopic diffusion anisotropy found with CODIVIDE. The discrepancies could be explained by the NODDI tortuosity assumption, which enforces a connection between the neurite density and the mean diffusivity of tissue. Our results suggest that this assumption invalid, which leads to a NODDI neurite density that is inconsistent between LTE and STE data. Using simulations, we demonstrate that the NODDI assumptions result in parameter bias that precludes the use of NODDI to map neurite density. With CODIVIDE, we found high levels of microscopic anisotropy in white matter, intermediate levels in structures such as the thalamus and the putamen, and low levels in the cortex and in gliomas. We conclude that accurate mapping of microscopic anisotropy requires data acquired with variable shape of the b-tensor.
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| 2. |
- Lampinen, Björn, et al.
(författare)
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Optimal experimental design for filter exchange imaging: Apparent exchange rate measurements in the healthy brain and in intracranial tumors.
- 2017
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 77:3, s. 1104-1114
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Filter exchange imaging (FEXI) is sensitive to the rate of diffusional water exchange, which depends, eg, on the cell membrane permeability. The aim was to optimize and analyze the ability of FEXI to infer differences in the apparent exchange rate (AXR) in the brain between two populations.METHODS: A FEXI protocol was optimized for minimal measurement variance in the AXR. The AXR variance was investigated by test-retest acquisitions in six brain regions in 18 healthy volunteers. Preoperative FEXI data and postoperative microphotos were obtained in six meningiomas and five astrocytomas.RESULTS: Protocol optimization reduced the coefficient of variation of AXR by approximately 40%. Test-retest AXR values were heterogeneous across normal brain regions, from 0.3 ± 0.2 s-1 in the corpus callosum to 1.8 ± 0.3 s-1 in the frontal white matter. According to analysis of statistical power, in all brain regions except one, group differences of 0.3-0.5 s-1 in the AXR can be inferred using 5 to 10 subjects per group. An AXR difference of this magnitude was observed between meningiomas (0.6 ± 0.1 s-1 ) and astrocytomas (1.0 ± 0.3 s-1 ).CONCLUSIONS: With the optimized protocol, FEXI has the ability to infer relevant differences in the AXR between two populations for small group sizes. Magn Reson Med 77:1104-1114, 2017.
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| 3. |
- Lampinen, Björn, et al.
(författare)
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Probing brain tissue microstructure with MRI: principles, challenges, and the role of multidimensional diffusion-relaxation encoding.
- 2023
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Ingår i: NeuroImage. - 1095-9572. ; 282
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Tidskriftsartikel (refereegranskat)abstract
- Diffusion MRI uses the random displacement of water molecules to sensitize the signal to brain microstructure and to properties such as the density and shape of cells. Microstructure modeling techniques aim to estimate these properties from acquired data by separating the signal between virtual tissue 'compartments' such as the intra-neurite and the extra-cellular space. A key challenge is that the diffusion MRI signal is relatively featureless compared with the complexity of brain tissue. Another challenge is that the tissue microstructure is wildly different within the gray and white matter of the brain. In this review, we use results from multidimensional diffusion encoding techniques to discuss these challenges and their tentative solutions. Multidimensional encoding increases the information content of the data by varying not only the b-value and the encoding direction but also additional experimental parameters such as the shape of the b-tensor and the echo time. Three main insights have emerged from such encoding. First, multidimensional data contradict common model assumptions on diffusion and T2 relaxation, and illustrates how the use of these assumptions cause erroneous interpretations in both healthy brain and pathology. Second, many model assumptions can be dispensed with if data are acquired with multidimensional encoding. The necessary data can be easily acquired in vivo using protocols optimized to minimize Cramér-Rao lower bounds. Third, microscopic diffusion anisotropy reflects the presence of axons but not dendrites. This insight stands in contrast to current 'neurite models' of brain tissue, which assume that axons in white matter and dendrites in gray matter feature highly similar diffusion. Nevertheless, as an axon-based contrast, microscopic anisotropy can differentiate gray and white matter when myelin alterations confound conventional MRI contrasts.
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| 4. |
- 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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| 5. |
- Lampinen, Björn, et al.
(författare)
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Time dependence in diffusion MRI predicts tissue outcome in ischemic stroke patients
- 2021
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 86:2, s. 754-764
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Reperfusion therapy enables effective treatment of ischemic stroke presenting within 4–6 hours. However, tissue progression from ischemia to infarction is variable, and some patients benefit from treatment up until 24 hours. Improved imaging techniques are needed to identify these patients. Here, it was hypothesized that time dependence in diffusion MRI may predict tissue outcome in ischemic stroke. Methods: Diffusion MRI data were acquired with multiple diffusion times in five non-reperfused patients at 2, 9, and 100 days after stroke onset. Maps of “rate of kurtosis change” (k), mean kurtosis, ADC, and fractional anisotropy were derived. The ADC maps defined lesions, normal-appearing tissue, and the lesion tissue that would either be infarcted or remain viable by day 100. Diffusion parameters were compared (1) between lesions and normal-appearing tissue, and (2) between lesion tissue that would be infarcted or remain viable. Results: Positive values of k were observed within stroke lesions on day 2 (P =.001) and on day 9 (P =.023), indicating diffusional exchange. On day 100, high ADC values indicated infarction of 50 ± 20% of the lesion volumes. Tissue infarction was predicted by high k values both on day 2 (P =.026) and on day 9 (P =.046), by low mean kurtosis values on day 2 (P =.043), and by low fractional anisotropy values on day 9 (P =.029), but not by low ADC values. Conclusions: Diffusion time dependence predicted tissue outcome in ischemic stroke more accurately than the ADC, and may be useful for predicting reperfusion benefit.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Rydelius, Anna, et al.
(författare)
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Diffusion tensor imaging in glioblastoma patients treated with volumetric modulated arc radiotherapy : a longitudinal study
- 2022
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 61:6, s. 680-687
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chemo- and radiotherapy (RT) is standard treatment for patients with high-grade glioma, but may cause side-effects on the patient's cognitive function.AIM: Use of diffusion tensor imaging (DTI) to investigate the longitudinal changes in normal-appearing brain tissue in glioblastoma patients undergoing modern arc-based RT with volumetric modulated arc therapy (VMAT) or helical tomotherapy.MATERIALS AND METHODS: The study included 27 patients newly diagnosed with glioblastoma and planned for VMAT or tomotherapy. All subjects underwent magnetic resonance imaging at the start of RT and at week 3, 6, 15, and 26. Fourteen subjects were additionally imaged at week 52. The DTI data were co-registered to the dose distribution maps. Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were assessed in the corpus callosum, the centrum semiovale, the hippocampus, and the amygdala.RESULTS: Significant longitudinal changes in FA, MD, and RD were mainly found in the corpus callosum. In the other examined brain structures, only sparse and transient changes were seen. No consistent correlations were found between biodose, age, or gender and changes in DTI parameters.CONCLUSION: Longitudinal changes in MD, FA, and RD were observed but only in a limited number of brain structures and the changes were smaller than expected from literature. The results suggest that modern, arc-based RT may have less negative effect on normal-appearing parts of the brain tissue up to 12 months after radiotherapy.
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| 9. |
- Spotorno, Nicola, et al.
(författare)
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Relationship between cortical iron and tau aggregation in Alzheimer's disease
- 2020
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 143:5, s. 1341-1349
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Tidskriftsartikel (refereegranskat)abstract
- A growing body of evidence suggests that the dysregulation of neuronal iron may play a critical role in Alzheimer's disease. Recent MRI studies have established a relationship between iron accumulation and amyloid-β aggregation. The present study provides further insight demonstrating a relationship between iron and tau accumulation using magnetic resonance-based quantitative susceptibility mapping and tau-PET in n = 236 subjects with amyloid-β pathology (from the Swedish BioFINDER-2 study). Both voxel-wise and regional analyses showed a consistent association between differences in bulk magnetic susceptibility, which can be primarily ascribed to an increase in iron content, and tau-PET signal in regions known to be affected in Alzheimer's disease. Subsequent analyses revealed that quantitative susceptibility specifically mediates the relationship between tau-PET and cortical atrophy measures, thus suggesting a modulatory effect of iron burden on the disease process. We also found evidence suggesting the relationship between quantitative susceptibility and tau-PET is stronger in younger participants (age ≤ 65). Together, these results provide in vivo evidence of an association between iron deposition and both tau aggregation and neurodegeneration, which help advance our understanding of the role of iron dysregulation in the Alzheimer's disease aetiology.
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| 10. |
- Surova, Yulia, et al.
(författare)
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Alteration of putaminal fractional anisotropy in Parkinson’s disease : a longitudinal diffusion kurtosis imaging study
- 2018
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Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 60:3, s. 247-254
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In Parkinson’s disease (PD), pathological microstructural changes occur that may be detected using diffusion magnetic resonance imaging (dMRI). However, there are few longitudinal studies that explore the effect of disease progression on diffusion indices. Methods: We prospectively included 76 patients with PD and 38 healthy controls (HC), all of whom underwent diffusion kurtosis imaging (DKI) as part of the prospective Swedish BioFINDER study at baseline and 2 years later. Annualized rates of change in DKI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK), were estimated in the gray matter (GM) by placing regions of interest (ROIs) in the basal ganglia and the thalamus, and in the white matter (WM) by tract-based spatial statistics (TBSS) analysis. Results: When adjusting for potential confounding factors (age, gender, baseline-follow-up interval, and software upgrade of MRI scanner), only a decrease in FA in the putamen of PD patients (β = − 0.248, P < .01) over 2 years was significantly different from the changes observed in HC over the same time period. This 2-year decrease in FA in the putamen in PD correlated with higher l-dopa equivalent dose at baseline (Spearman’s rho = .399, P < .0001). Conclusion: The study indicates that in PD microstructural changes in the putamen occur selectively over a 2-year period and can be detected with DKI.
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