HF patients exhibit cognitive deficits in the domains of attention and memory. MTA but not white matter lesion load seems to be related to cognitive impairment.

PET of amino acid transport and metabolism may be more accurate than conventional neuroimaging in differentiating recurrent gliomas from radiation-induced tissue changes. α-11C-methyl-l-tryptophan (11C-AMT) is an amino acid PET tracer that is not incorporated into proteins but accumulates in gliomas, mainly because of tumoral transport and metabolism via the immunomodulatory kynurenine pathway. The aim of this study was to evaluate the usefulness of 11C-AMT PET supplemented by tracer kinetic analysis for distinguishing recurrent gliomas from radiation injury. Methods Twenty-two 11C-AMT PET scans were obtained in adult patients who presented with a lesion suggestive of tumor recurrence on conventional MRI 1–6 y (mean, 3 y) after resection and postsurgical radiation of a World Health Organization grade II–IV glioma. Lesional standardized uptake values were calculated, as well as lesion-to-contralateral cortex ratios and 2 kinetic 11C-AMT PET parameters (volume of distribution [VD], characterizing tracer transport, and unidirectional uptake rate [K]). Tumor was differentiated from radiation-injured tissue by histopathology (n = 13) or 1-y clinical and MRI follow-up (n = 9). Accuracy of tumor detection by PET variables was assessed by receiver-operating-characteristic analysis. Results All 11C-AMT PET parameters were higher in tumors (n = 12) than in radiation injury (n = 10) (P ≤ 0.012 in all comparisons). The lesion-to-cortex K-ratio most accurately identified tumor recurrence, with highly significant differences both in the whole group (P < 0.0001) and in lesions with histologic verification (P = 0.006); the area under the receiver-operating-characteristic curve was 0.99. A lesion-to-cortex K-ratio threshold of 1.39 (i.e., a 39% increase) correctly differentiated tumors from radiation injury in all but 1 case (100% sensitivity and 91% specificity). In tumors that were high-grade initially (n = 15), a higher lesion-to-cortex K-ratio threshold completely separated recurrent tumors (all K-ratios ≥ 1.70) from radiation injury (all K-ratios < 1.50) (100% sensitivity and specificity). Conclusion Kinetic analysis of dynamic 11C-AMT PET images may accurately differentiate between recurrent World Health Organization grade II–IV infiltrating gliomas and radiation injury. Separation of unidirectional uptake rates from transport can enhance the differentiating accuracy of 11C-AMT PET. Applying the same approach to other amino acid PET tracers might also improve their ability to differentiate recurrent gliomas from radiation injury.

Summary The spatial relationship between an intracranial EEG-defined epileptic focus and cortical hypometabolism on glucose PET has not been precisely described. In order to quantitatively evaluate the hypothesis that ictal seizure onset and/or rapid seizure propagation, detected by subdural EEG monitoring, commonly involves normometabolic cortex adjacent to hypometabolic cortical regions, we applied a novel, landmark-constrained conformal mapping approach in 14 children with refractory neocortical epilepsy. The 3D brain surface was parcellated into finite cortical elements (FCEs), and hypometabolism was defined using lobe- and side-specific asymmetry indices derived from normal adult controls. The severity and location of hypometabolic areas vs. ictal intracranial EEG abnormalities were compared on the 3D brain surface. Hypometabolism was more severe in the seizure onset zone than in cortical areas covered by non-onset electrodes. However, similar proportions of the onset electrodes were located over and adjacent to (within 2 cm) hypometabolic regions (46% vs. 41%, respectively), whereas rapid seizure spread electrodes preferred these “adjacent areas” rather than the hypometabolic area itself (51% vs. 22%). On average, 58% of the hypometabolic regions had no early seizure involvement. These findings strongly support that the seizure onset zone often extends from hypometabolic to adjacent normometabolic cortex, while large portions of hypometabolic cortex are not involved in seizure onset or early propagation. The clinical utility of FDG PET in guiding subdural electrode placement in neocortical epilepsy could be greatly enhanced by extending grid coverage to at least 2 cm beyond hypometabolic cortex, when feasible.

Dysembryoplastic neuroepithelial tumors (DNTs) are typically hypometabolic but can show increased amino acid uptake on positron emission tomography (PET). To better understand mechanisms of amino acid accumulation in epileptogenic DNTs, we combined quantitative α-[11C]methyl-L-tryptophan (AMT) PET with tumor immunohistochemistry. Standardized uptake values (SUVs) of AMT and glucose were measured in 11 children with temporal lobe DNT. Additional quantification for AMT transport and metabolism was performed in 9 DNTs. Tumor specimens were immunostained for the L-type amino acid transporter 1 (LAT1) and indoleamine 2,3-dioxygenase (IDO), a key enzyme of the immunomodulatory kynurenine pathway. All 11 tumors showed glucose hypometabolism, while mean AMT SUVs were higher than normal cortex in eight DNTs. Further quantification showed increased AMT transport in seven and high AMT metabolic rates in three DNTs. Two patients showing extratumoral cortical increases of AMT SUV had persistent seizures despite complete tumor resection. Resected DNTs showed moderate to strong LAT1 and mild to moderate IDO immunoreactivity, with the strongest expression in tumor vessels. These results indicate that accumulation of tryptophan in DNTs is driven by high amino acid transport, mediated by LAT1, which can provide the substrate for tumoral tryptophan metabolism through the kynurenine pathway, that can produce epileptogenic metabolites. Increased AMT uptake can extend to extratumoral cortex, and presence of such cortical regions may increase the likelihood of recurrent seizures following surgical excision of DNTs.

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SUMMARYPurpose: To investigate clinical correlates and longitudinal course of interictal focal cortical glucose hypermetabolism in children with Sturge-Weber syndrome (SWS). Methods: Fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 60 children (age range 3 months to 15.2 years) with Sturge-Weber syndrome and epilepsy were assessed prospectively and serially for focal hypo-or hypermetabolism. Thirty-two patients had two or more consecutive PET scans. Age, seizure variables, and the occurrence of epilepsy surgery were compared between patients with and without focal hypermetabolism. The severity of focal hypermetabolism was also assessed and correlated with seizure variables. Key Findings: Interictal cortical glucose hypermetabolism, ipsilateral to the angioma, was seen in nine patients, with the most common location in the frontal lobe. Age was lower in patients with hypermetabolism than in those without (p = 0.022). In addition, time difference between the onset of first seizure and the first PET scan was much shorter in children with increased glucose metabolism than in those without (mean: 1.0 vs. 3.6 years; p = 0.019). Increased metabolism was transient and switched to hypometabolism in all five children where follow-up scans were available. Focal glucose hypermetabolism occurred in 28% of children younger than the age of 2 years. Children with transient hypermetabolism had a higher rate of subsequent epilepsy surgery as compared to those without hypermetabolism (p = 0.039). Significance: Interictal glucose hypermetabolism in young children with SWS is most often seen within a short time before or after the onset of first clinical seizures, that is, the presumed period of epileptogenesis. Increased glucose metabolism detected by PET predicts future demise of the affected cortex based on a progressive loss of metabolism and may be an imaging marker of the most malignant cases of intractable epilepsy requiring surgery in SWS.

Tag der mündlichen Prüfung: 15.07.2015Der Promovend ist Arzt. Für meine Eltern und meine EhefrauThe science of today is the technology of tomorrow.

BACKGROUND AND PURPOSE:Thalamocortical connections play a crucial role in complex cognitive functioning, and several neuropsychiatric disorders may involve aberrant thalamocortical circuitry. Here, we quantified the cortical pattern and age-related changes of thalamocortical connections by using probabilistic tractography in children and adolescents. We hypothesized that detectable asymmetry (leftϾright) exists in thalamocortical fiber connections and the connectivity increases with age during maturation.