| 1. |
- Palmqvist, Sebastian, et al.
(författare)
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Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease
- 2015
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 85:14, s. 1240-1249
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p < 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.
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| 2. |
- 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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| 3. |
- Falk Delgado, Anna, et al.
(författare)
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Diffusion kurtosis imaging of gliomas grades II and III : a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation
- 2017
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Ingår i: Radiology and Oncology. - : Walter de Gruyter GmbH. - 1318-2099 .- 1581-3207. ; 51:2, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- Background. 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).Patients and methods. 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.Results. 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.Conclusions. 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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| 4. |
- Follin, Cecilia, et al.
(författare)
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Hypothalamic dysfunction revealed by magnetic resonance diffusion tensor imaging in childhood leukemia survivors treated with cranial radiotherapy but not in craniopharyngeoma survivors
- 2016
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Konferensbidrag (refereegranskat)abstract
- Background: Metabolic complications with obesity are frequent in childhood acute lymphoblastic leukemia (ALL) survivors treated with cranial radiotherapy (CRT). Childhood onset Craniopharyngioma (CP) survivors without hypothalamic (HT) involvement are spared gross obesity. Magnetic resonance diffusion tensor imaging (DTI) provides information of microstructure function of the brain and quantified as fractional anisotrophy (FA), mean diffusivity (MD), axial and radial diffusivity (AD, RD). Since MD in HT is reportedly impaired (increased) in obese compared to non-obese subjects, we investigated DTI in the HT.Methods: Twenty nine ALL survivors on hormone supplementation were investigated 34 years after CRT (24 Gy). 17 CO-CP survivors with hormone supplementation but without HT damage were investigated. Comparisons were made with these two patient populations to 27 matched controls regarding DTI parameters in the HT and for BMI, fat mass, fat free mass and waist/hip measurements.Results: We recorded reduced FA (0.27 vs 0.29, P=0.04), and increased MD (1.13 vs 1.00, P<0.001), AD (1.41 vs 1.25, P<0.001), and RD (0.99 vs 0.86, P<0.001) in the right HT and increased MD (1.42 vs 1.25, P<0.001), AD (1.75 vs 1.58, P<0.001), and RD (1.25 vs 1.04, P<0.001) in left HT in ALL survivors compared to matched controls. The CPs showed no difference in the HT for these parameters compared to controls. ALL survivors with a BMI ≥ 25 showed elevated MD (P=0.03) and AD (P=0.02) compared to ALL survivors with a BMI < 25 and compared to controls with BMI ≥ 25 in the right HT. This was not the case in CP survivors or in controls.Conclusions: Thirty four years after CRT for ALL, DTI measures are deranged in the HT. ALL survivors with a BMI ≥ 25 were presented with worse HT dysfunction. CP survivors were unaffected. The present data suggests changes in the microstructure of the HT in these ALL survivors.
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| 5. |
- Follin, Cecilia, et al.
(författare)
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Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy–a diffusional kurtosis study
- 2019
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Ingår i: Acta Oncologica. - 0284-186X. ; 58:7, s. 1021-1028
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27–46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention (p <.001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all p <.05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum (p <.05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory (r = −0.40, p <.04). The left and right uncinate fasciculus (r = 0.6, p <.001), (r = −0.5, p <.02) as well as the right ventral cingulum (r = 0.5, p <.007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus (r = 0.3, r = 0.05, p =.02), and ventral cingulum (r = 0.3, p =.02) were associated with impaired results of episodic visual memory. Conclusion: ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.
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| 6. |
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| 7. |
- Askaner, Krister, et al.
(författare)
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Differentiation of Brain Metastases due to Primary Malignancy and Glioblastomas using Dynamic Susceptibility Contrast-Enhanced MR at 3T
- 2017
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Konferensbidrag (refereegranskat)abstract
- Purpose:To find out differences in cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSCE-MRI) in glioblastomas and cerebral metastases. The main purpose was to compare CBV maps between metastases with different primary malignancies. Furthermore the metastasis group was compared with the glioblastoma group.Method:Conventional imaging and DSCE-MRI using 3T MRI system was performed in 114 patients, 38 glioblastomas and 76 metastases, 32 lung, 12 breast, 12 melanoma, 10 gastrointestinal (GI), and 10 other. CBV values were measured in the solid tumor area, peritumoral edema, area adjacent to peritumoral edema, and in normal apparent white matter in contralateral semioval center. The four subgroups of metastases were compared with one-way ANOVA to determine differences in CBV of significance. CBV values in glioblastomas and metastases were then statistically compared using paired t-test. Receiver -operating characteristic analysis was used to determine optimal cut-off values when parameters showed statistical differences.Results:There were no significantly differences in CBV between the four subgroups of metastases. CBV in the peritumoral edema significantly differentiated metastases from glioblastomas, p=0.0001. CBV cutoff value of 2.3 yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 87, 87, 71, and 91% respectively. Conclusions:Differentiation of glioblastomas and metastases is possible using DSCE-MRI. No statistically significant differences regarding CBV between metastases from lung, breast, melanoma, and GI were detected.
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| 8. |
- Follin, Cecilia, et al.
(författare)
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Impaired brain metabolism and neurocognitive function in childhood leukemia survivors despite complete hormone supplementation in adulthood
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 73, s. 157-165
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Tidskriftsartikel (refereegranskat)abstract
- Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27–46) years. All were treated with a CRT dose of 24 Gy and 11 years (3–13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p < 0.001), memory (p < 0.001), learning capacity (p < 0.001), spatial ability (p < 0.001), executive functions and attention (p < 0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536 cm3, p < 0.001) and grey matter (GM) volumes (525 vs 555 cm3, p = 0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p = 0.004), WM NAA + NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p < 0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p = 0.001) and GM NAA + NAAG/Cr (1.28 vs 1.34, p = 0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p = 0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA + NAAG/Cr (r = −0.4, p = 0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group.
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| 9. |
- Follin, Cecilia, et al.
(författare)
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Microstructure alterations in the hypothalamus in cranially radiated childhood leukaemia survivors but not in craniopharyngioma patients unaffected by hypothalamic damage
- 2017
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 87:4, s. 359-366
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Metabolic complications are frequent in childhood leukaemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors. Design: Case-control study. Patients: Three groups were included: (i) 27 CRT treated ALL survivors on hormone supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without HT involvement and (iii) 27 matched controls. Measurements: DTI parameters of the HT were measured and body composition. Results: Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥25 than with BMI <25. Compared to controls, ALL survivors had reduced FA (P=.04), increased MD (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT, ALL survivors with a BMI ≥25 showed elevated MD (P=.03) and AD (P=.02) compared to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between CP survivors and controls. Conclusions: Long-term follow-up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT.
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| 10. |
- Hansson, Oskar, et al.
(författare)
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Blood-based NfL : A biomarker for differential diagnosis of parkinsonian disorder
- 2017
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 88:10, s. 930-937
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders. Methods: The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated. Results: We found strong correlations between blood and CSF concentrations of NfL (ρ ≥ 0.73-0.84, p ≤ 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p < 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81). Conclusions: Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics. Classification of evidence: This study provides Class III evidence that blood NfL levels discriminate between PD and APD.
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