Exit Options and the Europeanization of Healthcare: Cross-border Patient Mobility and Its Consequences for the German and Danish healthcare systems

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Identification of leptomeningeal metastasis-related proteins in cerebrospinal fluid of patients with breast cancer by a combination of MALDI-TOF, MALDI-FTICR and nanoLC-FTICR MS

Leptomeningeal metastasis (LM) is a devastating complication occurring in 5% of breast cancer patients. However, the current gold standard of diagnosis, namely microscopic examination of the cerebrospinal fluid (CSF), is false-negative in 25% of patients at the first lumbar puncture. In a previous study, we analyzed a set of 151 CSF samples (tryptic digests) by MALDI-TOF and detected peptide masses that were differentially expressed in breast cancer patients with LM. In the present study, we obtain for a limited number of samples exact masses for these peptides by MALDI-FTICR MS measurements. Identification of these peptides was performed by electrospray FTICR MS after separation by nano-scale LC. The database results were confirmed by targeted high mass accuracy measurements of the fragment ions in the FTICR cell. The combination of automated high-throughput MALDI-TOF measurements and analysis by FTICR MS leads to the identification of 17 peptides corresponding to 9 proteins. These include proteins that are operative in host-disease interaction, inflammation and immune defense (serotransferrin, alpha 1-antichymotrypsin, hemopexin, haptoglobin and transthyretin). Several of these proteins have been mentioned in the literature in relation to cancer. The identified proteins alpha1-antichymotrypsin and apolipoprotein E have been described in relation to Alzheimer's disease and brain cancer

Absorption mode FTICR mass spectrometry imaging

Fourier transform ion cyclotron resonance mass spectrometry offers the highest mass resolving power for molecular imaging experiments. This high mass resolving power ensures that closely spaced peaks at the same nominal mass are resolved for proper image generation. Typically higher magnetic fields are used to increase mass resolving power. However, a gain in mass resolving power can also be realized by phase correction of the data for absorption mode display. In addition to mass resolving power, absorption mode offers higher mass accuracy and signal-to-noise ratio over the conventional magnitude mode. Here, we present the first use of absorption mode for Fourier transform ion cyclotron resonance mass spectrometry imaging. The Autophaser algorithm is used to phase correct each spectrum (pixel) in the image, and then, these parameters are used by the Chameleon work-flow based data processing software to generate absorption mode “Datacubes” for image and spectral viewing. Absorption mode reveals new mass and spatial features that are not resolved in magnitude mode and results in improved selected ion image contrast