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  • DKFZ Publication Database  (3)
  • 1
    Abstract: OBJECTIVES: To differentiate between abnormal tumor vessels and regular brain vasculature using new quantitative measures in time-of-flight (TOF) MR angiography (MRA) data. MATERIALS AND METHODS: In this work time-of-flight (TOF) MR angiography data are acquired in 11 glioma patients to quantify vessel abnormality. Brain vessels are first segmented with a new algorithm, efficient monte-carlo image-analysis for the location of vascular entity (EMILOVE), and are then characterized in three brain regions: tumor, normal-appearing contralateral brain, and the total brain volume without the tumor. For characterization local vessel orientation angles and the dot product between local orientation vectors are calculated and averaged in the 3 regions. Additionally, correlation with histological and genetic markers is performed. RESULTS: Both the local vessel orientation angles and the dot product show a statistically significant difference (p 〈 0.005) between tumor vessels and normal brain vasculature. Furthermore, the connection to both histology and the gene expression of the tumor can be found-here, the measures were compared to the proliferation marker Ki-67 [MIB] and genome-wide expression analysis. The results in a subgroup indicate that the dot product measure may be correlated with activated genetic pathways. CONCLUSION: It is possible to define a measure of vessel abnormality based on local vessel orientation angles which can differentiate between normal brain vasculature and glioblastoma vessels.
    Type of Publication: Journal article published
    PubMed ID: 27097906
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  • 2
    Abstract: The evolving and highly heterogeneous nature of malignant brain tumors underlies their limited response to therapy and poor prognosis. In addition to genetic alterations, highly dynamic processes, such as transcriptional and metabolic reprogramming, play an important role in the development of tumor heterogeneity. The current study reports an adaptive mechanism in which the metabolic environment of malignant glioma drives transcriptional reprogramming. Multiregional analysis of a glioblastoma patient biopsy revealed a metabolic landscape marked by varying stages of hypoxia and creatine enrichment. Creatine treatment and metabolism was further shown to promote a synergistic effect through upregulation of the glycine cleavage system and chemical regulation of prolyl-hydroxylase domain. Consequently, creatine maintained a reduction of reactive oxygen species and change of the alpha-ketoglutarate/succinate ratio, leading to an inhibition of HIF signaling in primary tumor cell lines. These effects shifted the transcriptional pattern toward a proneural subtype and reduced the rate of cell migration and invasion in vitroImplications: Transcriptional subclasses of glioblastoma multiforme are heterogeneously distributed within the same tumor. This study uncovered a regulatory function of the tumor microenvironment by metabolism-driven transcriptional reprogramming in infiltrating glioma cells. Mol Cancer Res; 16(4); 655-68. (c)2018 AACR.
    Type of Publication: Journal article published
    PubMed ID: 29330292
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  • 3
    Keywords: analysis, ARTIFACTS, BEHAVIOR, brain, comparison, CONTRAST, DIFFERENCE, FIELD, FIELDS, Germany, HEAL
    Abstract: Background and purpose: Hyperecho-turbo spin-echo (Hypertse) Sequences were developed to reduce the specific absorption rate (Sar), Especially at high fields such as 3t and above. The purpose of this study was to quantitatively and qualitatively assess the detection of neuroradiologic pathologies by hypertse in comparison with standard turbo spin-echo (Tse180 degrees) Sequences. Materials and methods: Tse180 degrees and hypertse images with parameters adapted for equal t2 contrast were acquired on a 3t whole-body system in 51 patients with 54 cerebral pathologies. Region-of-interest analysis was performed of signal intensities of pathologies, normal white and gray matter, csf, and the sd of noise. Signal intensity-to-noise ratios (Snrs) And contrast-to-noise ratios (Cnrs) For healthy tissues and pathologies were determined. A qualitative rating concerning artifacts, lesion conspicuity, and image quality was performed by 2 experienced neuroradiologists. Results: Hypertse sequences were equivalent to standard tse180 degrees sequences for the cnr of pathologies and of the contrast between gray and white matter. The snr of gray and white matter and csf were also the same. The cnrs of the pathologies in hypertse and tse180 degrees images were strongly correlated with each other (R = 0.93, P = .001). The visual rating of images revealed no significant differences between hypertse and tse180 degrees. Conclusion: Hypertse sequences proved to be qualitatively and quantitatively equivalent to tse180 degrees sequences in the detection of high- and low-signal-intensity lesions. They provide equal cnr of pathologies and of gray minus white matter and reduce the imaging restrictions of conventional tse180 degrees imposed by sar limitations at 3t
    Type of Publication: Journal article published
    PubMed ID: 18321987
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