| 1. |
- Appel, Lieuwe, et al.
(författare)
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Use of C-11-PE2I PET in Differential Diagnosis of Parkinsonian Disorders
- 2015
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:2, s. 234-242
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Tidskriftsartikel (refereegranskat)abstract
- In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using I-123-FP-CIT (I-123-N-omega-fluoropropyl- 2 beta-carbomethoxy-3 beta-(4-iodophenyl) nortropane, or I-123-ioflupane) SPECT and F-18-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic C-11-PE2I (N-(3-iodoprop-2E-enyl)-2 beta-carbomethoxy-3 beta-(4-methyl-phenyl) nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BPND]) and relative cerebral blood flow (relative delivery [R-1]) at voxel level. This study aimed to evaluate the validity of C-11-PE2I PET against the dual-modality approach using I-123-FP-CIT SPECT and F-18-FDG PET.Methods: Sixteen patients with parkinsonian disorders had a dual examination with F-18-FDG PET and I-123-FP-CIT SPECT following clinical routines and additionally an experimental C-11-PE2I PET scan. Parametric BPND and R-1 images were generated using receptor parametric mapping with the cerebellum as a reference. T1-weighted MR imaging was used for automated definition of volumes of interest (VOI). The DAT VOIs included the basal ganglia, whereas the overall brain functional activity was examined using VOIs across the brain. BPND and R-1 values were compared with normalized I-123-FP-CIT and F-18-FDG uptake values, respectively, using Pearson correlations and regression analyses. In addition, 2 masked interpreters evaluated the images visually, in both the routine and the experimental datasets, for comparison of patient diagnoses.Results: Parametric C-11-PE2I BPND and R-1 images showed high consistency with I-123-FP-CIT SPECT and F-18-FDG PET images. Correlations between C-11-PE2I BPND and I-123-FP-CIT uptake ratios were 0.97 and 0.76 in the putamen and caudate nucleus, respectively. Regional C-11-PE2I R-1 values were moderately to highly correlated with normalized F-18-FDG values (range, 0.61-0.94). Visual assessment of DAT availability showed a high consistency between C-11-PE2I BPND and I-123-FP-CIT images, whereas the consistency was somewhat lower for appraisal of overall brain functional activity using I-123-FP-CIT and F-18-FDG images. Substantial differences were found between clinical diagnosis and both neuro-imaging diagnoses.Conclusion: A single, dynamic C-11-PE2I PET investigation is a powerful alternative to a dual examination with I-123-FP-CIT SPECT and F-18-FDG PET for differential diagnosis of parkinsonian disorders. A large-scale patient study is, however, needed to further investigate distinct pathologic patterns in overall brain functional activity for various parkinsonian disorders.
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| 2. |
- Asklund, Thomas, et al.
(författare)
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PET response and tumor stabilization under erlotinib and bevacizumab treatment of an intracranial lesion non-invasively diagnosed as likely chordoma
- 2011
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Ingår i: Clinical Neuropathology. - Deisenhofen : Dustri-Verlag Feistle. - 0722-5091. ; 30:5, s. 242-246
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Chordoma is a rare and a slow-growing tumor originating from the notochord and commonly localized in the skull base. Surgery and occasionally radiotherapy have emerged as the treatments of choice. In the relapsed situations available treatment options are strictly limited; however, recently molecularly targeted agents have been proposed to be of potential beneficial value. THE CASE: A 63-year-old male presenting with seizures and an extradural mass in the left brain hemisphere. An attempt to resect the tumor was followed by severe bradycardia when manipulating with the dura and therefore discontinued. It was considered too hazardous even to take a biopsy specimen. The tumor was considered radiologically and macroscopically as a chordoma. As the tumor progressed after radiotherapy, chemotherapy with erlotinib in combination with cetuximab was initiated. This treatment was interrupted due to progressive disease and toxicity. However, combination treatment with erlotinib and bevacizumab normalized the uptake of [11C]methionine PET signal and resulted in a slight tumor shrinkage on MRI. The patient is still (March 2011) free of symptoms, without cranial nerve deficits or seizures. DISCUSSION: This report shows that erlotinib and bevacizumab in combination may completely quench the transport of the essential amino acid methionine to a treatment refractory intracranial tumor bearing radiological and clinical characteristics of a chordoma. Further studies are necessary to establish this strategy as a treatment option for this indication.
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| 3. |
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| 4. |
- 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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| 5. |
- Danfors, Torsten, et al.
(författare)
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Akutneurologi
- 2006
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Ingår i: Neurologi. - : Liber AB, Stockholm. - 9789147053131 ; , s. 568-
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Danfors, Torsten, et al.
(författare)
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Epileptic seizures and survival in early disease of grade 2 gliomas
- 2009
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 16:7, s. 823-831
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeThe aims of this study were (i) to determine the correlation between seizure activity and the metabolic rate of the tumour measured by 11Cmethionine PET (MET PET) in patients with grade 2 gliomas, and (ii) to assess the prognostic impact of early seizure manifestations on patient survival.MethodsIn this retrospective review, early seizure manifestations were studied in 101 patients with supratentorial grade 2 gliomas subjected to MET PET as part of the pretreatment tumour investigation. Seizure manifestations as a variable was then used in multivariate survival analyses, together with established prognostic factors for this patient group.ResultsOf all 101 cases, 88 patients had seizures at tumour presentation. Fortyseven were seizure free at the early stage of the disease, whereas 54 had recurrent seizures. Patients with seizures at tumour presentation had a more favourable outcome before and after (P = 0.006) adjustment for conventional prognostic factors. However, for those who continued to have seizures early in the disease, the outcome was worse (P = 0.003). We found no significant correlation between MET PET and the seizure manifestations of the patients.ConclusionThe presence and termination of early seizure manifestations may be favourable prognostic factors in patients with low-grade gliomas.
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| 7. |
- Danfors, Torsten, et al.
(författare)
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Increased neurokinin-1 receptor availability in temporal lobe epilepsy : A positron emission tomography study using [(11)C]GR205171
- 2011
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 97:1-2, s. 183-189
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability. METHODS: A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping. RESULTS: Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset. CONCLUSION: Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.
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| 8. |
- Danfors, Torsten, et al.
(författare)
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Positron emission tomography with 11C-D-deprenyl in patients with rheumatoid arthritis. Evaluation of knee joint inflammation before and after intra-articular glucocorticoid treatment
- 1997
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Ingår i: Scandinavian Journal of Rheumatology. - 0300-9742 .- 1502-7732. ; 26:1, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Seven patients with arthritic disease and with clinical signs of inflammation of the knee joint, were investigated with positron emission tomography (PET) after injection of [N-methyl-11C]-D-deprenyl. Two healthy volunteers were included as controls. In five patients the investigation was repeated after an intra-articular injection of glucocorticoids. All patients showed very high uptake of the tracer in the paraarticular structures of the joint. After treatment there was approximately a 50% reduction of the uptake in the treated knees, both in the high uptake regions and in the surrounding soft tissues. No change was observed in the non-treated knees. In the healthy volunteers, only soft tissue surrounding the joint showed an uptake of the tracer, but at a magnitude which was 6-8 times lower than the high uptake regions in the arthritis patients. Although the mechanisms for the high uptake of 11C-D-deprenyl in affected joints of patients with arthritis is not clear, the present work points to a potential of PET for the assessment of disease intensity and monitoring of treatment.
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| 9. |
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| 10. |
- Danfors, Torsten, et al.
(författare)
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Tetrahydrobiopterin in the treatment of children with autistic disorder. A double-blind placebo-controlled crossover study
- 2005
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Ingår i: Journal of Clinical Psychopharmacology. - 0271-0749 .- 1533-712X. ; 25:5, s. 485-489
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Tidskriftsartikel (refereegranskat)abstract
- Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.
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