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11C Molecular Imaging in Focal Epilepsy
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2012. , s. 58
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 814
Nyckelord [en]
positron emission tomography, methionine, NK1, substance p, flumazenil, deprenyl, pk11195, phosphoimager, autoradiography, TBI, traumatic brain injury, iron chloride, ferrous chloride
Nationell ämneskategori
Neurologi Radiologi och bildbehandling
Forskningsämne
Neurologi; Radiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-179954ISBN: 978-91-554-8475-0 (tryckt)OAI: oai:DiVA.org:uu-179954DiVA, id: diva2:552115
Disputation
2012-10-26, Enghoff salen, Akademiska sjukhuset, ing 50, bv, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2012-10-04 Skapad: 2012-08-27 Senast uppdaterad: 2018-06-18Bibliografiskt granskad
Delarbeten
1. Epileptic seizures and survival in early disease of grade 2 gliomas
Öppna denna publikation i ny flik eller fönster >>Epileptic seizures and survival in early disease of grade 2 gliomas
2009 (Engelska)Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, nr 7, s. 823-831Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background and purpose

The 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.

Methods

In 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.

Results

Of 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.

Conclusion

The presence and termination of early seizure manifestations may be favourable prognostic factors in patients with low-grade gliomas.

 

Nyckelord
11C methionine positron emission tomography, epileptic seizures, low-grade glioma, survival
Nationell ämneskategori
Neurologi
Forskningsämne
Neurologi
Identifikatorer
urn:nbn:se:uu:diva-105434 (URN)10.1111/j.1468-1331.2009.02599.x (DOI)000266637000012 ()
Tillgänglig från: 2009-06-03 Skapad: 2009-06-03 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
2. Increased neurokinin-1 receptor availability in temporal lobe epilepsy: A positron emission tomography study using [(11)C]GR205171
Öppna denna publikation i ny flik eller fönster >>Increased neurokinin-1 receptor availability in temporal lobe epilepsy: A positron emission tomography study using [(11)C]GR205171
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2011 (Engelska)Ingår i: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 97, nr 1-2, s. 183-189Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Nyckelord
Epilepsy, PET, NK1, Substance P, TLE
Nationell ämneskategori
Neurologi
Forskningsämne
Neurologi
Identifikatorer
urn:nbn:se:uu:diva-159946 (URN)10.1016/j.eplepsyres.2011.08.006 (DOI)00297873800021 ()21925840 (PubMedID)
Tillgänglig från: 2011-10-12 Skapad: 2011-10-12 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
3. Relative Cerbral Blood Flow Measurement using dynamic Flumazenil-PET may Replace Fluorodeoxyglucose-PET in Epilepsy Surgical Investigations
Öppna denna publikation i ny flik eller fönster >>Relative Cerbral Blood Flow Measurement using dynamic Flumazenil-PET may Replace Fluorodeoxyglucose-PET in Epilepsy Surgical Investigations
2012 (Engelska)Artikel i tidskrift (Övrigt vetenskapligt) Submitted
Nationell ämneskategori
Neurovetenskaper Annan medicinsk grundvetenskap
Forskningsämne
Neurologi
Identifikatorer
urn:nbn:se:uu:diva-180846 (URN)
Tillgänglig från: 2012-09-11 Skapad: 2012-09-11 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
4. 11C-autoradiographic studies of dynamic changes in glial cells and benzodiazepine receptor binding in a model of posttraumatic epilepsy
Öppna denna publikation i ny flik eller fönster >>11C-autoradiographic studies of dynamic changes in glial cells and benzodiazepine receptor binding in a model of posttraumatic epilepsy
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
urn:nbn:se:uu:diva-180847 (URN)
Tillgänglig från: 2012-09-11 Skapad: 2012-09-11 Senast uppdaterad: 2018-06-18

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