Susceptibility-weighted angiography visualizes hypoxia in cerebral veins.

OBJECTIVES: The objective of this study was to evaluate the influence of short- and long-term hypoxia on the depiction of cerebral veins in the susceptibility-weighted angiography (SWAN) sequence. MATERIALS AND METHODS: In the context of a study on brain adaptation mechanisms to hypoxia, 16 healthy men (aged 20-28 years) were studied through magnetic resonance imaging (MRI) under room air conditions, short-term-hypoxia (7 minutes before and during the MRI scan), and long-term hypoxia (8.5 hours before and during the MRI scan). Oxygen saturation was continuously measured using a finger-mounted pulse oximeter. Two independent blinded readers compared the 3 scans of each participant and graded the SWAN source images and minimum intensity projections according to the size, number, and signal intensity of the cerebral veins. Signal intensities of deep cerebral veins were measured, and signal intensity proportions of deep cerebral veins to different parenchymal brain regions were calculated. RESULTS: Nine subjects could be included in the study. In all of them, both readers correctly distinguished the 2 hypoxia scans from the baseline scan, grading the SWAN images acquired under hypoxic conditions as visualizing cerebral veins more prominently. Signal intensities of the deep cerebral veins and signal intensity proportions were significantly lower in the hypoxia scans. No significant differences between short-term and long-term hypoxia were found on visual inspections and signal intensity measurements. This correlated with the results of the pulse oximetry: mean O2 saturation values were 97.9% ± 1.2% (baseline), 84.1% ± 3.8% (short-term hypoxia), and 82.8% ± 4.4% (long-term hypoxia), respectively. CONCLUSIONS: Hypoxia leads to visible and measurable changes in cerebral veins as depicted through SWAN. Possible clinical implications of this finding include stroke and tumor imaging and need further investigation.

Complex level alterations of the 2f(1)-f(2) distortion product due to hypoxia.

OBJECTIVE: For diagnostic purposes and a better understanding of the pathophysiology of inner ear hearing disorders it would be of great interest to have parameters available that indicate inner ear hypoxia. In animal studies typical hypoxia-related alterations of the 2f1-f2 distortion product otoacoustic emissions (DPOAE) such as a reversible level decrease and destabilization could be demonstrated. The goal of this study was to investigate whether these hypoxia-associated alterations can also be observed in humans because this might help develop a new diagnostic tool for patients with inner ear disorders. METHODS: In 16 volunteers DPOAE levels were continuously measured at first under normal room air conditions, during and after 8.5h of oxygen deprivation (13% O2) and during re-oxygenation. Saturation of oxygen of arterial blood (SaO2) was monitored. RESULTS: The mean SaO2 during the hypoxic interval was 78%. A significant decrease in DPOAE level under hypoxia occurred in five different test persons at one or more frequencies (f2=1, 1.5, 2, 3, and 4kHz). A destabilization of the DPOAE level with considerable fluctuations during hypoxia was observed in nine subjects at one or more frequencies. Furthermore, the so called 'post hypoxia effect' could be observed in five participants. CONCLUSION: The observations made here have been described similarly in animal studies and seem to be characteristic of metabolic disorders of the cochlea caused by hypoxia. To our knowledge, this is the first study to examine DPOAE level alterations over time in humans under conditions of normobaric hypoxia. If DPOAE destabilization is observed in a clinical setting in patients with certain inner ear hearing disorders hypoxia can be suspected as one underlying pathophysiological cause which might influence treatment decisions.

New similarity search based glioma grading.

INTRODUCTION: MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading. METHODS: We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences. For each patient, a so-called tumor feature vector (= probability-based classifier) was defined and used for grading. Biopsy was used as gold standard, and similarity based grading was compared to grading solely based on CE-T1w. RESULTS: Accuracy, sensitivity, and specificity of pure CE-T1w based glioma grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor grading allowed differentiation between low-grade (I or II) and high-grade (III) gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and 87.0%. CONCLUSION: Our findings indicate that integration of perfusion parameters and CE-T1w information in a semi-automatic similarity search based analysis improves the potential of MR-based glioma grading compared to CE-T1w data alone.

No fear no risk! Human risk behavior is affected by chemosensory anxiety signals.

An important aspect of cognitive functioning is decision-making, which depends on the correct interpretation of emotional processes. High trait anxiety has been associated with increased risk taking behavior in decision-making tasks. An interesting fact is that anxiety and anxiety-related chemosignals as well as decision-making share similar regions of neuronal activation. In order to ascertain if chemosensory anxiety signals have similar effects on risk taking behavior of healthy participants as high trait anxiety we used a novel computerized decision-making task, called Haegler's Risk Game (HRG). This task measures risk taking behavior based on contingencies and can be played repeatedly without a learning effect. To obtain chemosensory signals the sweat of 21 male donors was collected in a high rope course (anxiety condition). For the chemosensory control condition sweat was collected during an ergometer workout (exercise condition). In a double-blind study, 30 healthy recipients (16 females) had to play HRG while being exposed to sweat samples or empty control samples (control condition) in three sessions of randomized order. Comparison of the risk taking behavior of the three conditions showed significantly higher risk taking behavior in participants for the most risky choices during the anxiety condition compared to the control conditions. Additionally, recipients showed significantly higher latency before making their decision in the most risky choices during the anxiety condition. This experiment gives evidence that chemosensory anxiety signals are communicated between humans thereby increasing participants' risk taking behavior.

QuantiSpec--Quantitative mass spectrometry data analysis of (15)N-metabolically labeled proteins.

For relative protein quantitation by mass spectrometry we metabolically labeled E. coli bacteria with (15)N-enriched diets. Proteins extracted from (15)N-labeled and unlabeled E. coli bacteria were mixed, separated by two-dimensional gel electrophoresis and enzymatically digested. The resulting tryptic peptides were analyzed by MALDI mass spectrometry. For the relative protein quantitation we developed fully automated software, QuantiSpec (Quantitative Mass Spectrometry Analysis Software), which uses data from MALDI TOF mass spectrometry and the Mascot database search engine. QuantiSpec detects natural as well as partially or fully labeled peptide isotope distributions. For each identified peptide the (15)N incorporation rate is determined by comparing the experimental to a set of theoretical isotope patterns based on the peptide sequence. Relative quantitation is accomplished by calculating the signal intensity ratios for each (14)N/(15)N peptide pair.

Regulation of proteins mediating neurodegeneration in experimental autoimmune encephalomyelitis and multiple sclerosis.

Multiple sclerosis is characterized by inflammatory demyelination and axonal loss as pathophysiological correlates of relapsing activity and progressive development of clinical disability. The molecular processes involved in this pathogenesis are still unclear as they are quite complex and heterogeneous. In this article we present protein expression analysis of brain and spinal cord tissues from different models of murine experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model for multiple sclerosis. We observed a number of EAE-specific protein expression and PTM differences. Proteome analysis was extended to multiple sclerosis specimens in order to validate the EAE findings. Our findings suggest the regulation of a number of proteins that shed light on the molecular mechanisms of the disease processes taking place in EAE and multiple sclerosis. We found consistent modulation of proteins including serum amyloid P component, sirtuin 2, dihydropyrimidinase-related protein family proteins, stathmin 1, creatine kinase B and chloride intracellular channel protein 1. Functional classification of the proteins by database and the literature mining reveals their association with neuronal development and myelinogenesis, suggesting possible disease processes that mediate neurodegeneration.

The quest for brain disorder biomarkers.

The identification of disease markers in tissues and body fluids requires an extensive and thorough analysis of its protein constituents. In our efforts to identify biomarkers for affective and neurological disorders we are pursuing several different strategies. On one hand we are using animal models that represent defined phenotypes characteristic for the respective disorder in humans. In addition, we are analyzing human specimens from carefully phenotyped patient groups. Several fractions representing different protein classes from human cerebrospinal fluid obtained by lumbar puncture are used for this purpose. Our biomarker identification efforts range from classical proteomics approaches such as two dimensional gel electrophoresis and mass spectrometry to phage display screens with cerebrospinal fluid antibodies.