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Galldiks N.,Max Planck Institute for Neurological Research | Galldiks N.,University of Cologne | Galldiks N.,University of Munster | Kracht L.W.,Max Planck Institute for Neurological Research | And 21 more authors.
Molecular Imaging | Year: 2010

We present two patients with glioblastoma with an unusually stable clinical course and long-term survival who were treated after surgery and radiotherapy with adjuvant temozolomide (TMZ) chemotherapy for 17 and 20 cycles, respectively. Afterward, adjuvant TMZ chemotherapy was discontinued in one patient and the dosage of TMZ was reduced in the other. In addition to clinical status and magnetic resonance imaging, the biologic activity of the tumors was monitored by repeated methyl- 11C-l-methionine (MET) and 3'-deoxy-3'- 18F-fl uorothymidine (FLT) positron emission tomography (PET) studies in these patients. In these patients, repeated MET-and FLT-PET imaging documented complete response to the initial treatment regimen, including resection, radiation, and TMZ, and during the course of the disease, recurrent, uncontrollable tumor activity. Continuation or dose escalation of TMZ in both patients was shown to be ineffective to overcome the metabolic activity of the tumor. Our data suggest that repeated MET- and FLT-PET imaging provide information on the biologic activity of a tumor that is highly useful to monitor and detect changes in activity. © 2010 BC Decker Inc. Source


Chen G.,Vanderbilt University | Wang F.,Vanderbilt University | Dillenburger B.C.,Vanderbilt University | Dillenburger B.C.,MPI for Neurological Research | And 5 more authors.
Magnetic Resonance Imaging | Year: 2012

Functional magnetic resonance imaging (fMRI) at high magnetic field strength can suffer from serious degradation of image quality because of motion and physiological noise, as well as spatial distortions and signal losses due to susceptibility effects. Overcoming such limitations is essential for sensitive detection and reliable interpretation of fMRI data. These issues are particularly problematic in studies of awake animals. As part of our initial efforts to study functional brain activations in awake, behaving monkeys using fMRI at 4.7 T, we have developed acquisition and analysis procedures to improve image quality with encouraging results. We evaluated the influence of two main variables on image quality. First, we show how important the level of behavioral training is for obtaining good data stability and high temporal signal-to-noise ratios. In initial sessions, our typical scan session lasted 1.5 h, partitioned into short (<10 min) runs. During reward periods and breaks between runs, the monkey exhibited movements resulting in considerable image misregistrations. After a few months of extensive behavioral training, we were able to increase the length of individual runs and the total length of each session. The monkey learned to wait until the end of a block for fluid reward, resulting in longer periods of continuous acquisition. Each additional 60 training sessions extended the duration of each session by 60 min, culminating, after about 140 training sessions, in sessions that last about 4 h. As a result, the average translational movement decreased from over 500 μm to less than 80 μm, a displacement close to that observed in anesthetized monkeys scanned in a 7-T horizontal scanner. Another major source of distortion at high fields arises from susceptibility variations. To reduce such artifacts, we used segmented gradient-echo echo-planar imaging (EPI) sequences. Increasing the number of segments significantly decreased susceptibility artifacts and image distortion. Comparisons of images from functional runs using four segments with those using a single-shot EPI sequence revealed a roughly twofold improvement in functional signal-to-noise-ratio and 50% decrease in distortion. These methods enabled reliable detection of neural activation and permitted blood-oxygenation-level-dependent-based mapping of early visual areas in monkeys using a volume coil. In summary, both extensive behavioral training of monkeys and application of segmented gradient-echo EPI sequence improved signal-to-noise ratio and image quality. Understanding the effects these factors have is important for the application of high field imaging methods to the detection of submillimeter functional structures in the awake monkey brain. © 2012 Elsevier Inc. Source


Zempel H.,German Center for Neurodegenerative Diseases | Luedtke J.,German Center for Neurodegenerative Diseases | Luedtke J.,MPI for Neurological Research | Kumar Y.,German Center for Neurodegenerative Diseases | And 9 more authors.
EMBO Journal | Year: 2013

Mislocalization and aggregation of Aβ and Tau combined with loss of synapses and microtubules (MTs) are hallmarks of Alzheimer disease. We exposed mature primary neurons to Aβ oligomers and analysed changes in the Tau/MT system. MT breakdown occurs in dendrites invaded by Tau (Tau missorting) and is mediated by spastin, an MT-severing enzyme. Spastin is recruited by MT polyglutamylation, induced by Tau missorting triggered translocalization of TTLL6 (Tubulin-Tyrosine-Ligase-Like-6) into dendrites. Consequences are spine loss and mitochondria and neurofilament mislocalization. Missorted Tau is not axonally derived, as shown by axonal retention of photoconvertible Dendra2-Tau, but newly synthesized. Recovery from Aβ insult occurs after Aβ oligomers lose their toxicity and requires the kinase MARK (Microtubule- Affinity-Regulating-Kinase). In neurons derived from Tau-knockout mice, MTs and synapses are resistant to Aβ toxicity because TTLL6 mislocalization and MT polyglutamylation are prevented; hence no spastin recruitment and no MT breakdown occur, enabling faster recovery. Reintroduction of Tau re-establishes Aβ-induced toxicity in TauKO neurons, which requires phosphorylation of Tau's KXGS motifs. Transgenic mice overexpressing Tau show TTLL6 translocalization into dendrites and decreased MT stability. The results provide a rationale for MT stabilization as a therapeutic approach. © 2013 European Molecular Biology Organization. Source


Berres A.,University of Kaiserslautern | Goldau M.,University of Leipzig | Goldau M.,MPI for Neurological Research | Tittgemeyer M.,MPI for Neurological Research | And 2 more authors.
EG VCBM 2012 - Eurographics Workshop on Visual Computing for Biology and Medicine | Year: 2012

Displaying neurological data from multiple imaging modalities in anatomical context is a challenging task in biomedical visualization. We present an application-driven approach, which solves the visibility issues of simultaneous presentation of focus and context. The tractogram (a scalar field indicating a connectivity score between voxels) is visualized by nested surface layers, providing an overview of long-range connectivity. Unique dataset features are reflected by value-based opacity, and further enhanced by depth cues. Anatomical context is given as an illustrative, threedimensional rendering of the cortex complemented with textured slices. Two user studies were performed to evaluate our methods and we adapted our techniques based on their feedback. With the presented methods, the nature of the tractogram becomes clear even in static images, while it allows to perceive the information and the context simultaneously. Our methods can be applied to a wide range of data, as they can be adapted to different data ranges and requirements very easily. © The Eurographics Association 2012. Source


Waerzeggers Y.,Westfaelische Wilhelms University | Monfared P.,MPI for Neurological Research | Viel T.,Westfaelische Wilhelms University | Faust A.,Westfaelische Wilhelms University | And 6 more authors.
British Journal of Radiology | Year: 2011

A deeper understanding of the role of specific genes, proteins, pathways and networks in health and disease, coupled with the development of technologies to assay these molecules and pathways in patients, promises to revolutionise the practice of clinical medicine. Especially the discovery and development of novel drugs targeted to disease-specific alterations could benefit significantly from non-invasive imaging techniques assessing the dynamics of specific disease-related parameters. Here we review the application of imaging biomarkers in the management of patients with brain tumours, especially malignant glioma. In our other review we focused on imaging biomarkers of general biochemical and physiological processes related with tumour growth such as energy, protein, DNA and membrane metabolism, vascular function, hypoxia and cell death. In this part of the review, we will discuss the use of imaging biomarkers of specific disease-related molecular genetic alterations such as apoptosis, angiogenesis, cell membrane receptors and signalling pathways and their application in targeted therapies. © 2011 The British Institute of Radiology. Source

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