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1.
  • Delgado, Anna Falk, et al. (författare)
  • Glioma grade discrimination with MR diffusion kurtosis imaging : A meta-Analysis of diagnostic accuracy
  • 2018
  • Ingår i: Radiology. - : Radiological Society of North America. - 0033-8419 .- 1527-1315. ; 287:1, s. 119-127
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To assess the diagnostic test accuracy and sources of heterogeneity for the discriminative potential of diffusion kurtosis imaging (DKI) to differentiate low-grade glioma (LGG) (World Health Organization [WHO] grade II) from high-grade glioma (HGG) (WHO grade III or IV). Materials and Methods: The Cochrane Library, Embase, Medline, and the Web of Science Core Collection were systematically searched by two librarians. Retrieved hits were screened for inclusion and were evaluated with the revised tool for quality assessment for diagnostic accuracy studies (commonly known as QUADAS-2) by two researchers. Statistical analysis comprised a random-effects model with associated heterogeneity analysis for mean differences in mean kurtosis (MK) in patients with LGG or HGG. A bivariate restricted maximum likelihood estimation method was used to describe the summary receiver operating characteristics curve and bivariate meta-regression. Results: Ten studies involving 430 patients were included. The mean difference in MK between LGG and HGG was 0.17 (95% confidence interval [CI]: 0.11, 0.22) with a z score equal to 5.86 (P < .001). The statistical heterogeneity was explained by glioma subtype, echo time, and the proportion of recurrent glioma versus primary glioma. The pooled area under the curve was 0.94 for discrimination of HGG from LGG, with 0.85 (95% CI: 0.74, 0.92) sensitivity and 0.92 (95% CI: 0.81, 0.96) specificity. Heterogeneity was driven by neuropathologic subtype and DKI technique. Conclusion: MK shows high diagnostic accuracy in the discrimination of LGG from HGG.
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2.
  • Falk Delgado, Alberto, et al. (författare)
  • Arterial spin labeling MR imaging for differentiation between high- and low-grade glioma - A meta-analysis
  • 2018
  • Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20:11, s. 1450-1461
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Arterial spin labeling is an MR imaging technique that measures cerebral blood flow (CBF) noninvasively. The aim of the study is to assess the diagnostic performance of arterial spin labeling (ASL) MR imaging for differentiation between high-grade glioma and low-grade glioma. Methods. Cochrane Library, Embase, Medline, and Web of Science Core Collection were searched. Study selection ended November 2017. This study was prospectively registered in PROSPERO (CRD42017080885). Two authors screened all titles and abstracts for possible inclusion. Data were extracted independently by 2 authors. Bivariate random effects meta-analysis was used to describe summary receiver operating characteristics. Trial sequential analysis (TSA) was performed. Results. In total, 15 studies with 505 patients were included. The diagnostic performance of ASL CBF for glioma grading was 0.90 with summary sensitivity 0.89 (0.79-0.90) and specificity 0.80 (0.72-0.89). The diagnostic performance was similar between pulsed ASL (AUC 0.90) with a sensitivity 0.85 (0.71-0.91) and specificity 0.83 (0.69- 0.92) and pseudocontinuous ASL (AUC 0.88) with a sensitivity 0.86 (0.79-0.91) and specificity 0.80 (0.65-0.87). In astrocytomas, the diagnostic performance was 0.89 with sensitivity 0.86 (0.79 to 0.91) and specificity 0.79 (0.63 to 0.89). Sensitivity analysis confirmed the robustness of the findings. TSA revealed that the meta-analysis was adequately powered. Conclusion. Arterial spin labeling MR imaging had an excellent diagnostic accuracy for differentiation between high-grade and low-grade glioma. Given its low cost, non-invasiveness, and efficacy, ASL MR imaging should be considered for implementation in the routine workup of patients with glioma.
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3.
  • Pereira, Joana B., et al. (författare)
  • Abnormal structural brain connectome in individuals with preclinical Alzheimer's disease
  • 2018
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211. ; 28:10, s. 3638-3649
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease has a long preclinical phase during which amyloid pathology and neurodegeneration accumulate in the brain without producing overt cognitive deficits. It is currently unclear whether these early disease stages are associated with a progressive disruption in the communication between brain regions that subsequently leads to cognitive decline and dementia. In this study we assessed the organization of structural networks in cognitively normal (CN) individuals harboring amyloid pathology (A+N-), neurodegeneration (A-N+), or both (A+N+) from the prospective and longitudinal Swedish BioFINDER study. We combined graph theory with diffusion tensor imaging to investigate integration, segregation, and centrality measures in the brain connectome in the previous groups. At baseline, our findings revealed a disrupted network topology characterized by longer paths, lower efficiency, increased clustering and modularity in CN A-N+ and CN A+N+, but not in CN A+N-. After 2 years, CN A+N+ showed significant abnormalities in all global network measures, whereas CN A-N+ only showed abnormalities in the global efficiency. Network connectivity and organization were associated with memory in CN A+N+ individuals. Altogether, our findings suggest that amyloid pathology is not sufficient to disrupt structural network topology, whereas neurodegeneration is.
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4.
  • Hakansson, C., et al. (författare)
  • Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience
  • 2021
  • Ingår i: European Radiology. - : Springer. - 0938-7994. ; 31:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. Methods Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's kappa (dichotomized data), Cohen's kappa(w), and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as kappa/kappa(w) >= 0.80 and ICC >= 0.80 (significance level at 95% CI >= 0.65). Results Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's kappa. All raters achieved adequate agreement expressed as Cohen's kappa(w) and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. Conclusion We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences.
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5.
  • Johansson, M., et al. (författare)
  • Apathy and anxiety are early markers of Alzheimer's disease
  • 2020
  • Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 85, s. 74-82
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, we investigated associations between neuropsychiatric symptoms (i.e., apathy, anxiety, and depression) and cerebral atrophy, white matter lesions (WML), beta-amyloid (A beta) deposition, and cognitive decline in a nondemented sample. 104 cognitively unimpaired and 53 subjects with mild cognitive impairment were followed for up to 4 years within the Swedish BioFINDER study. Neuropsychiatric assessments included the Hospital Anxiety and Depression Scale and the Apathy Evaluation Scale. Magnetic resonance imaging and F-18-flutemetamol-positron emission tomography quantified brain atrophy, WML, and A beta deposition. Mini-Mental State Examination assessed longitudinal global cognition. Regression analyses were used to test for associations. Apathy and anxiety were shown related to A beta deposition and predicted cognitive decline. Anxiety also interacted with amyloid status to predict faster cognitive deterioration. Apathy was further related to frontotemporal and subcortical atrophy, as well as WML. To conclude, the associations between apathy and anxiety with A beta deposition and cognitive decline point to these symptoms as early clinical manifestations of Alzheimer's disease. (C) 2019 Elsevier Inc. All rights reserved.
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6.
  • Spotorno, N., et al. (författare)
  • Plasma neurofilament light protein correlates with diffusion tensor imaging metrics in frontotemporal dementia
  • 2020
  • Ingår i: Plos One. - : Public Library of Science. - 1932-6203. ; 15:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process.
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7.
  • Voevodskaya, O., et al. (författare)
  • Brain myoinositol as a potential marker of amyloid-related pathology: A longitudinal study
  • 2019
  • Ingår i: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 92:5, s. E395-E405
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline.MethodsIn this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline -amyloid (A), and between MRS and the longitudinal Mini-Mental State Examination, accounting for APOE, age, and sex.ResultsWhile baseline MRS metabolites were similar in A positive (A+) and negative (A-) individuals, in the A+ group, the estimated rate of change was +1.9%/y for myo-inositol (mI)/creatine (Cr) and -2.0%/y for N-acetylaspartate (NAA)/mI. In the A- group, mI/Cr and NAA/mI yearly change was -0.05% and +1.2%; however, this was not significant across time points. The mild cognitive impairment A+ group showed the steepest MRS changes, with an estimated rate of +2.93%/y (p = 0.07) for mI/Cr and -3.55%/y (p < 0.01) for NAA/mI. Furthermore, in the entire cohort, we found that A+ individuals with low baseline NAA/mI had a significantly higher rate of cognitive decline than A+ individuals with high baseline NAA/mI.ConclusionWe demonstrate that the longitudinal change in mI/Cr and NAA/mI is associated with underlying amyloid pathology. MRS may be a useful noninvasive marker of A-related processes over time. In addition, we show that in A+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.
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8.
  • Wahlund, L. O., et al. (författare)
  • Imaging biomarkers of dementia: recommended visual rating scales with teaching cases
  • 2017
  • Ingår i: Insights into Imaging. - : Springer Berlin/Heidelberg. - 1869-4101. ; 8:1, s. 79-90
  • Tidskriftsartikel (refereegranskat)abstract
    • The diagnostic work up of dementia may benefit from structured reporting of CT and/or MRI and the use of standardised visual rating scales. We advocate a more widespread use of standardised scales as part of the workflow in clinical and research evaluation of dementia. We propose routine clinical use of rating scales for medial temporal atrophy (MTA), global cortical atrophy (GCA) and white matter hyperintensities (WMH). These scales can be used for evaluation of both CT and MRI and are efficient in routine imaging assessment in dementia, and may improve the accuracy of diagnosis. Our review provides detailed imaging examples of rating increments in each of these scales and a separate teaching file. The radiologist should relate visual ratings to the clinical assessment and other biomarkers to assist the clinician in the diagnostic decision.
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9.
  • Ygland, Emil, et al. (författare)
  • Slowly progressive dementia caused by MAPT R406W mutations : longitudinal report on a new kindred and systematic review
  • 2018
  • Ingår i: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 10
  • Forskningsöversikt (refereegranskat)abstract
    • Background: The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with Alzheimer's disease-like clinical features. Methods: We compiled clinical data from a new Swedish kindred with R406W mutation. Seven family members were followed longitudinally for up to 22 years. Radiological examinations were performed in six family members and neuropathological examinations in three. We systematically reviewed the literature and compiled clinical, radiological, and neuropathological data on 63 previously described R406W heterozygotes and 3 homozygotes. Results: For all cases combined, the median age of onset was 56 years and the median disease duration was 13 years. Memory impairment was the most frequent symptom, behavioral disturbance and language impairment were less common, and Parkinsonism was rare. Disease progression was most often slow. The most frequent clinical diagnosis was Alzheimer's disease. R406W homozygotes had an earlier age at onset and a higher frequency of behavioral symptoms and Parkinsonism than heterozygotes. In the new Swedish kindred, a consistent imaging finding was ventromedial temporal lobe atrophy, which was evident also in early disease stages as a widening of the collateral sulcus with ensuing atrophy of the parahippocampal gyrus. Unlike previously published R406W carriers, all three autopsied patients from the novel family showed neuropathological similarities with progressive supranuclear palsy, with predominant four-repeat (exon 10+) tau isoform (4R) tauopathy and neurofibrillary tangles accentuated in the basal-medial temporal lobe. Amyloid-beta pathology was absent. Conclusions: Dominance of 4R over three-repeat (exon 10-) tau isoforms contrasts with earlier reports of R406W patients and was not sufficiently explained by the presence of H1/H2 haplotypes in two of the autopsied patients. R406W patients often show a long course of disease with marked memory deficits. Both our neuropathological results and our imaging findings revealed that the ventromedial temporal lobes were extensively affected in the disease. We suggest that this area may represent the point of origin of tau deposition in this disease with relatively isolated tauopathy.
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10.
  • Delgado, Anna F., et al. (författare)
  • Diffusion kurtosis imaging of gliomas grades II and III - A study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation
  • 2017
  • Ingår i: Radiology and Oncology. - : Onkoloski Institut Ljubljana. - 1318-2099. ; 51:2, s. 121-129
  • Tidskriftsartikel (refereegranskat)abstract
    • Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas). Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=<0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.
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