| 1. |
- Fahlström, Markus, et al.
(författare)
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Evaluation of Arterial Spin Labeling MRI : Comparison with 15O-Water PET on an Integrated PET/MR Scanner
- 2021
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Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.
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| 2. |
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| 3. |
- Danfors, Torsten, 1964-
(författare)
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11C Molecular Imaging in Focal Epilepsy
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epilepsy is a common neurological disease affecting 6 million people in Europe. Early prevention and accurate diagnosis and treatment are of importance to obtain seizure freedom. In this thesis new applications of carbon-11-labelled tracers in PET and autoradiographic studies were explored in focal epilepsy.Patients with low-grade gliomas often experience epileptic seizures. A retrospective PET-study assessing seizure activity, metabolic rate measured with 11C-methionine and other known prognostic factors was performed in patients with glioma. No correlation was found between seizure activity and uptake of methionine. The presence and termination of early seizures was a favourable prognostic factor.Activation of the neurokinin-1 (NK1) receptor by substance P (SP) induces epileptic activity. PET with the NK1 receptor antagonist GR205171 was performed in patients with temporal lobe epilepsy (TLE) and healthy controls. In TLE patients an increased NK1 receptor availability was found in both hemispheres, most pronounced in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptors and seizure frequency was observed in ipsilateral medial structures consistent with an intrinsic network using the NK1-SP receptor system for transmission of seizure activity.The uptake of 18F-fluoro-deoxy-glucose (FDG) is related to cerebral blood flow (CBF). Previously, methods to estimate blood flow from dynamic PET data have been described. A retrospective study was conducted in 15 patients undergoing epilepsy surgery investigation, including PET with 11C-FDG and 11C-Flumazenil (FMZ). The dynamic FMZ dataset and pharmacokinetic modeling with a multilinear reference tissue model were used to determine images of relative CBF. Agreement between data of FDG and CBF was analyzed showing a close association between interictal brain metabolism and relative CBF.Epilepsy often occurs after traumatic brain injuries. Changes in glia and inhibitory neuronal cells contribute to the chain of events leading to seizures. Autoradiography with 11C-PK11195, 11C-L-deprenyl and 11C-Flumazenil in an animal model of posttraumatic epilepsy studied the temporal and spatial distribution of microglia, astrocytes and GABAergic neurons. Results showed an instant increase in microglial activity that subsequently normalized, a late formation of astrogliosis and an instant and prolonged decease in GABA binding. The model can be used to visualize pathophysiological events during the epileptogenesis.
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| 4. |
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| 5. |
- de la Vega, Maria Pagnon, et al.
(författare)
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The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation
- 2021
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:606
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Tidskriftsartikel (refereegranskat)abstract
- Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid beta (A beta). Here, we describe the Uppsala APP mutation (Delta 690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) A beta 42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing beta-secretase cleavage and affecting alpha-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated A beta, A beta Upp1-42(Delta 19-24), accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain.
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| 6. |
- Fällmar, David, et al.
(författare)
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Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.
- 2018
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Ingår i: American Journal of Nuclear Medicine and Molecular Imaging. - 2160-8407. ; 8:4, s. 239-246
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Tidskriftsartikel (refereegranskat)abstract
- Neuroimaging is a central part of diagnostic work-up of patients with suspected neurodegenerative disease. FDG-PET can reveal pathological changes earlier and more reliably than morphological imaging. Diagnostic accuracy can be improved by constructing 3D SSP Z-score maps, showing patterns of significant deficits. During FDG-PET, the subject receives a moderate but not insignificant dose of ionizing radiation, and a dose reduction with retained image quality is desirable. With lower dose, repeated examinations can become a useful tool for monitoring disease progress and potential effects of disease-modifying interventions. The aim of this study was to evaluate Z-maps created from low-dose and normal-dose FDG-PET of the brain, with quantitative and qualitative methods. Nine patients with neurodegenerative disorders were prospectively enrolled and nine age-matched controls were recruited through advertising. All subjects (n=18) underwent two FDG-PET scans on separate occasions; a routine and a low-dose scan. The routine dosage of FDG was 3 MBq/kg, and low dosage was 0.75 MBq/kg. 3D-SSP images showing Z-scores of < -1.96 were created from 10-minute summations. The study was comprised of a quantitative part comparing the Z-scores, and a qualitative part where experienced nuclear medicine specialists visually assessed the images. Regarding the quantitative part, Bland-Altman analysis showed a slight constant bias (0.206). Regarding qualitative discrimination between patients and controls, the performance between normal- and low-dose were equal, both showing 72% sensitivity, 83% specificity and 78% accuracy. In this study, visual assessment of 3D-SSP Z-score maps from low-dose FDG-PET provided diagnostic information highly comparable to normal-dose, with minor quantitative discrepancies.
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| 7. |
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| 8. |
- Jonasson, My, et al.
(författare)
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Striatal dopamine transporter and receptor availability correlate with relative cerebral blood flow measured with [11C]PE2I, [18F]FE-PE2I and [11C]raclopride PET in healthy individuals
- 2023
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 43:7, s. 1206-1215
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this retrospective study was to investigate relationships between relative cerebral blood flow and striatal dopamine transporter and dopamine D2/3 availability in healthy subjects. The data comprised dynamic PET scans with two dopamine transporter tracers [11C]PE2I (n = 20) and [18F]FE-PE2I (n = 20) and the D2/3 tracer [11C]raclopride (n = 18). Subjects with a [11C]PE2I scan also underwent a dynamic scan with the serotonin transporter tracer [11C]DASB. Binding potential (BPND) and relative tracer delivery (R1) values were calculated on regional and voxel-level. Striatal R1 and BPND values were correlated, using either an MRI-based volume of interest (VOI) or an isocontour VOI based on the parametric BPND image. An inter-tracer comparison between [11C]PE2I BPND and [11C]DASB R1 was done on a VOI-level and simulations were performed to investigate whether the constraints of the modeling could cause correlation of the parameters. A positive association was found between BPND and R1 for all three dopamine tracers. A similar correlation was found for the inter-tracer correlation between [11C]PE2I BPND and [11C]DASB R1. Simulations showed that this relationship was not caused by cross-correlation between parameters in the kinetic model. In conclusion, these results suggest an association between resting-state striatal dopamine function and relative blood flow in healthy subjects.
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| 9. |
- Lindström, Elin, et al.
(författare)
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Evaluation of penalized likelihood estimation reconstruction on a digital time-of-flight PET/CT scanner for 18F-FDG whole-body examinations
- 2018
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 59:7, s. 1152-1158
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Tidskriftsartikel (refereegranskat)abstract
- The resolution and quantitative accuracy of PET are highly influenced by the reconstruction method. Penalized-likelihood estimation algorithms allow for fully convergent iterative reconstruction, generating a higher image contrast than ordered-subsets expectation maximization (OSEM) while limiting noise. In this study, a type of penalized reconstruction known as block-sequential regularized expectation maximization (BSREM) was compared with time-of-flight OSEM (TOF OSEM). Various strengths of noise penalization factor β were tested along with various acquisition durations and transaxial fields of view (FOVs) with the aim of evaluating the performance and clinical use of BSREM for 18F-FDG PET/CT, both quantitatively and in a qualitative visual evaluation. Methods: Eleven clinical whole-body 18F-FDG PET/CT examinations acquired on a digital TOF PET/CT scanner were included. The data were reconstructed using BSREM with point-spread function recovery and β-factors of 133, 267, 400, and 533—and using TOF OSEM with point-spread function—for various acquisition times per bed position and various FOVs. Noise level, signal-to-noise ratio (SNR), signal-to-background ratio (SBR), and SUV were analyzed. A masked evaluation of visual image quality, rating several aspects, was performed by 2 nuclear medicine physicians to complement the analysis. Results: The lowest levels of noise were reached with the highest β-factor, resulting in the highest SNR, which in turn resulted in the lowest SBR. A β-factor of 400 gave noise equivalent to TOF OSEM but produced a significant increase in SUVmax (11%), SNR (22%), and SBR (12%). BSREM with a β-factor of 533 at a decreased acquisition duration (2 min/bed position) was comparable to TOF OSEM at a full acquisition duration (3 min/bed position). Reconstructed FOV had an impact on BSREM outcome measures; SNR increased and SBR decreased when FOV was shifted from 70 to 50 cm. The evaluation of visual image quality resulted in similar scores for reconstructions, although a β-factor of 400 obtained the highest mean whereas a β-factor of 267 was ranked best in overall image quality, contrast, sharpness, and tumor detectability. Conclusion: In comparison with TOF OSEM, penalized BSREM reconstruction resulted in an increased tumor SUVmax and an improved SNR and SBR at a matched level of noise. BSREM allowed for a shorter acquisition than TOF OSEM, with equal image quality.
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| 10. |
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| 11. |
- Lindström, Elin, et al.
(författare)
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Image reconstruction methods affect software-aided assessment of pathologies of [18F]flutemetamol and [18F]FDG brain-PET examinations in patients with neurodegenerative diseases
- 2020
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Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess how some of the new developments in brain positron emission tomography (PET) image reconstruction affect quantitative measures and software-aided assessment of pathology in patients with neurodegenerative diseases. Methods: PET data were grouped into four cohorts: prodromal Alzheimer's disease patients and controls receiving [18F]flutemetamol, and neurodegenerative disease patients and controls receiving [18F]FDG PET scans. Reconstructed images were obtained by ordered-subsets expectation maximization (OSEM; 3 iterations (i), 16/34 subsets (s), 3/5-mm filter, ±time-of-flight (TOF), ±point-spread function (PSF)) and block-sequential regularized expectation maximization (BSREM; TOF, PSF, β-value 75–300). Standardized uptake value ratios (SUVR) and z-scores were calculated (CortexID Suite, GE Healthcare) using cerebellar gray matter, pons, whole cerebellum and whole brain as reference regions. Results: In controls, comparable results to the normal database were obtained with OSEM 3i/16 s 5-mm reconstruction. TOF, PSF and BSREM either increased or decreased the relative uptake difference to the normal subjects’ database within the software, depending on the tracer and chosen reference area, i.e. resulting in increased absolute z-scores. Normalizing to pons and whole brain for [18F]flutemetamol and [18F]FDG, respectively, increased absolute differences between reconstructions methods compared to normalizing to cerebellar gray matter and whole cerebellum when applying TOF, PSF and BSREM. Conclusions: Software-aided assessment of patient pathologies should be used with caution when employing other image reconstruction methods than those used for acquisition of the normal database.
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| 12. |
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| 13. |
- Niemelä, Valter, et al.
(författare)
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Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations
- 2020
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Ingår i: NEUROLOGY-GENETICS. - : LIPPINCOTT WILLIAMS & WILKINS. - 2376-7839. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden.MethodsClinical assessments, targeted genetic studies, neuroimaging with MRI, [F-18]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with I-123 FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectroscopy (MRS).ResultsFour patients living in Sweden but with different ethnical backgrounds were included. Their clinical features were variable. Biallelic VPS13A mutations were confirmed in all patients, including 3 novel mutations. All tested patients had either low or absent chorein levels. One patient had progressive caudate atrophy. Investigation using FDG-PET revealed severe bilateral striatal hypometabolism, and DaTscan SPECT displayed presynaptic dopaminergic deficiency in 3 patients. MRS demonstrated reduced N-acetylaspartate/creatine (Cr) ratio and mild elevation of both choline/Cr and combined glutamate and glutamine/Cr in the striatum in 1 case. One patient died during sleep, and another was treated with deep brain stimulation, which transiently attenuated feeding dystonia but not his gait disorder or chorea.ConclusionsLarger longitudinal neuroimaging studies with different modalities, particularly MRS, are needed to determine their potential role as biomarkers for ChAc.
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| 14. |
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| 15. |
- Syk, Mikaela, 1990-, et al.
(författare)
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Biological markers for CNS damage in a patient cohort with suspected autoimmune psychiatric disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: This study describes the prevalence of CNS damage biomarkers and other CNS pathology in a psychiatric patient cohort enriched for clinical red flags of suspected autoimmune psychiatric disease. The study further explores how CNS damage biomarkers relate to clinical red flags and psychiatric features. Methods: 127 patients were included in the study. A routine cerebrospinal fluid (CSF) analysis was performed and anti-neuronal antibodies were measured. CNS damage biomarkers (neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAp) and total Tau (t-Tau)) in CSF were related to proposed clinical red flags for autoimmune psychiatric disease, other psychiatric features and MRI and EEG findings. Results: Twenty-seven per cent had elevated levels of CNS damage biomarkers and 21% had basic CSF analysis alterations. Six per cent had anti-neuronal antibodies in serum and 2% in CSF. Fifty percent of patients examined with MRI (n=88) had signs of atrophy and 41% had white matter changes. Twenty-five percent of patients with EEG recordings (n=70) had pathological EEG findings. Elevated NfL, GFAp and t-Tau levels were associated with the presence of clinical red flags. Elevated GFAp and t-Tau were also associated with higher psychiatric symptom ratings.Conclusions: Pre-selection based on clinical red flags for autoimmune psychiatric disease identifies a population where 27% have CSF signs of CNS tissue damage, 21% have CSF alterations suggesting neuroinflammation or blood-brain barrier dysfunction and 6% have anti-neuronal antibodies. Moreover, pathological levels of NfL, GFAp or t-Tau in CSF may be related to distinctive red flags and patterns of psychiatric manifestations.
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| 16. |
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| 17. |
- Xiong, Mengfei, et al.
(författare)
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Evaluation of [11C]UCB-A positron emission tomography in human brains
- 2024
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Ingår i: EJNMMI Research. - : Springer. - 2191-219X. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In preclinical studies, the positron emission tomography (PET) imaging with [C-11]UCB-A provided promising results for imaging synaptic vesicle protein 2A (SV2A) as a proxy for synaptic density. This paper reports the first-in-human [C-11]UCB-A PET study to characterise its kinetics in healthy subjects and further evaluate SV2A-specific binding.Results: Twelve healthy subjects underwent 90-min baseline [C-11]UCB-A scans with PET/MRI, with two subjects participating in an additional blocking scan with the same scanning procedure after a single dose of levetiracetam (1500 mg). Our results indicated abundant [C-11]UCB-A brain uptake across all cortical regions, with slow elimination. Kinetic modelling of [C-11]UCB-A PET using various compartment models suggested that the irreversible two-tissue compartment model best describes the kinetics of the radioactive tracer. Accordingly, the Patlak graphical analysis was used to simplify the analysis. The estimated SV2A occupancy determined by the Lassen plot was around 66%. Significant specific binding at baseline and comparable binding reduction as grey matter precludes the use of centrum semiovale as reference tissue.Conclusions: [C-11]UCB-A PET imaging enables quantifying SV2A in vivo. However, its slow kinetics require a long scan duration, which is impractical with the short half-life of carbon-11. Consequently, the slow kinetics and complicated quantification methods may restrict its use in humans.
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