Background Rest tremor is a hallmark of Parkinson’s disease (PD), but its pathogenesis remains incompletely understood. Nigro-striatal dopamine deficiency correlates best with bradykinesia, but not with tremor. Oscillating neurons in one or multiple localizations within the basal gangliathalamo-cortical loop may cause rest tremor, and an active contribution of the cerebellum and the cerebello-thalamo-cortical projections has been postulated. Objective To compare the pattern of grey matter volume in PD patients with and without tremor to identify structural correlates of rest tremor. Methods Voxel-based morphometry (VBM) of a high-resolution 3 Tesla, T1-weighted MR images, pre-processed according to an optimized protocol using SPM2, was performed in 24 patients with mild to moderate PD comparing local grey matter volume in patients with (n = 14) and without rest tremor (n = 10). Results Grey matter volume is decreased in the right quadrangular lobe and declive of the cerebellum in PD with tremor compared to those without (PFDR < 0.05). Conclusions These results demonstrate for the first time morphological changes in the cerebellum in PD patients with rest tremor and highlight the involvement of the cerebellum and cerebello- thalamo-cortical circuit in the pathogenesis of parkinsonian rest tremor.

Ziele: To design and to evaluate a framework allowing for software based, highly accurate registration of PET and MRI nearly whole-body imaging (from scull base to inguinal). Methode: A new approach to sequentially rigid and non-rigid registration of PET and MRI nearly whole-body imaging was applied: To determine the respective transformations Trigid and Tnon-rigid, first the CT-part of the PET/CT was registered at the MRI. Second the corresponding registration of PET and MRI was achieved by application of (Tnon-regid * Tregid) at the PET-part of the PET/CT.

Aim: To evaluate the in vitro and in vivo characteristics of [N-methyl-C-11]2-(4'-(methylaminophenyl)-benzothiazole ([C-11]BTA-1) as well as [N-methyl-C-11]2-(3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([C-11]3'-Me-BTA-1) as diagnostic markers of amyloid-beta (A beta) in Alzheimer's disease (AD). Material, methods: Brain uptake and clearance was determined in wild-type mice. Binding affinities (K,) of [C-11]BTA-1 and [C-11]3'-Me-BTA-1 for aggregated A beta(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [C-11]BTA-1 PET study of an AD patient and a healthy control was performed. Results: In mice brain uptake and clearance of [C-11]BTA-1 is compatible with the half life of C-11 (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [C-11]3'-Me-BTA-1 is too slow (2 min 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. K-j of [C-11]BTA-1 is 11 nmol/l and that of [C-11]3'-Me-BTA-1 27 nmol/l. Both radioligands label A beta selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of A beta plaques. The AD patient has a higher prefrontal, parietal and striatal [C-11]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [C-11]BTA-1 after 30min in plasma.[C-11]BTA-1 is favourable for in vivo imaging of A beta due to its rapid brain entry, sufficient clearance and good binding affinity for A beta. Conclusion: The ability to label A beta plaques in vivo in human subjects supports the suitability of [C-11]BTA-1 as a plaque imaging agent.

SummaryAim: [N-methyl-11C]2-(4'-(methylaminophenyl)-benzothiazole (11C-BTA-1) is a thioflavin-T derivative that has been one of the promising PET tracers for imaging of amyloid plaque distribution in the Alzheimer patients brain in vivo. The biodistribution and dosimetry of this tracer in humans is presented and compared to the results of a previous dosimetry and biodistribution study of another thioflavin-T derivative [N-methyl-11C]2-hydroxy-(4'-(methylaminophenyl)- benzothiazole (11C-OH-BTA-1) in baboons. Methods: Five subjects underwent 2D dynamic PET imaging. Source organs were segmented using a semiautomatic algorithm based on clustering. Residence times for each source organ were determined by analytical integration of an exponential fit of the time activity curves. Finally organ doses were estimated using the software OLINDA/EXM. Results: The administration of 286 ± 93 MBq 11C-BTA-1 was well tolerated by all subjects. Effective radiation dose was 4.3 μSv/MBq, range 3.6–5.0 μSv/MBq. In four of the five subjects the liver, in one of the subjects the gallbladder was the critical organ. Conclusion: The radiation burden of a single dose of 300 MBq 11C-BTA-1 is within the accepted limits for research purpose. In contrast to the previous non-human primate study revealing the gallbladder as the critical organ for 11C-6-OH-BTA-1, we found the liver as the critical organ in humans using 11C-BTA-1. Possible explanations may be (1) a reduced bile concentration of 11C-BTA-1 due to the absent OH-group or (2) a different hepatic metabolism of thioflavin derivatives in human and baboon.

Ziele: Um die Genauigkeit der Diagnose der Demenz vom Alzheimer-Typ weiter zu verbessern, eine frühere Diagnose zu ermöglichen und die Wirksamkeit potentieller Medikamente zu verifizieren wurden in den vergangenen Jahren intensive Anstrengungen unternommen mittels eines geeigneten PET-Tracers die Verteilungsmuster der Alzheimer-Plaques in vivo darzustellen. Es wurde gezeigt, dass einer der vielversprechensten PET-Tracer hierfür das Thioflavin-Derivat [N-methyl-11C]2-hydroxy-(4'-(methyl-aminophenyl)-benzothiazole ([11C]-BTA-1) ist.

Ziele: Die klinische Symptomatik des M.Parkinson lässt sich in eine primär akinetisch-rigide sowie eine primär tremor-dominate Form differenzieren.

Aims: Over the last years there has been great effort to develop novel in vivo amyloid-imaging radiotracers for use with positron emission tomography (PET) to allow noninvasive in vivo assessments of amyloid plaques. This might lead to a better understanding of amyloid deposition over the course of disease in Alzheimer's disease (AD), and might eventually provide a surrogate marker of potential antiamyloid therapies.

We used simultaneous electroencephalogram-functional magnetic resonance imaging (EEG-fMRI) and EEG-near infrared spectroscopy (NIRS) to investigate whether changes of the posterior EEG alpha rhythm are correlated with changes in local cerebral blood oxygenation. Cross-correlation analysis of slowly fluctuating, spontaneous rhythms in the EEG and the fMRI signal revealed an inverse relationship between alpha activity and the fMRI-blood oxygen level dependent signal in the occipital cortex. The NIRS-EEG measurements demonstrated a positive cross-correlation in occipital cortex between alpha activity and concentration changes of deoxygenated hemoglobin, which peaked at a relative shift of about 8 s. Our data suggest that alpha activity in the occipital cortex is associated with metabolic deactivation. Mapping of spontaneously synchronizing distributed neuronal networks is thus shown to be feasible.

In this study, the feasibility of dipole source localization (DSL) and coregistration with functional magnetic resonance imaging (fMRI) activation patterns on the basis of simultaneously acquired data is demonstrated. Brain activity was mapped during the performance of a somatosensory single reaction and a choice reaction task at high spatiotemporal resolution in six healthy subjects. The choice reaction task required a categorization of two different stimulus intensities, whereas for the single reaction task merely the perception of a tactile stimulus had to be confirmed by the subjects. An offline artifact correction algorithm was applied to 32-channel EEG data that were acquired between subsequent MRI scans. Using a multiple dipole approach, five distinct dipole sources were identified within areas of the somatosensory system. Coregistration of fMRI and DSL showed consistent spatial activation patterns with a mean distance of 9.2 ± 6.8 mm between dipole sources and fMRI activation maxima. However, since the number of fMRI activation sites exceeded the number of cerebral dipole sources, it was not possible to assign a dipole source to each fMRI activation site. Dipole moment time courses were consistent with previously reported results of similar experiments. A comparison of brain activation patterns during the two tasks with both fMRI and DSL indicated an involvement of the contralateral secondary somatosensory cortex in somatosensory categorization.

Cortical signal intensity changes due to brief (1 s) innocuous electrical stimuli applied to the second and fifth finger of the right hand were measured by means of fMRI at 1.5 T. The activation pattern in this event-related fMRI approach closely resembled that obtained in recent block-design studies. Activations were found in contralateral primary (SI) and bilaterally in secondary (SII) somato-sensory cortex as well as in posterior parietal cortex, insula, and supplementary motor area (SMA). In SI, the somatotopic organization of the hand area is demonstrated, more clearly to be seen in area 3b than in area 1 and 2. In conclusion, the feasibility to employ event-related somatosensory stimulation paradigms in fMRI studies is demonstrated.