Concentration gradients of monoamines, their precursors and metabolites in serial lumbar cerebrospinal fluid of neurologically healthy patients determined with a novel LC–MS/MS technique

Background: Potential biomarkers for neuropsychiatric disorders are cerebrospinal fluid (CSF) monoamines and their corresponding precursors and metabolites. During CSF sampling, CSF flows towards the lumbar sampling site from more cranial regions. To compare the results of studies in which different CSF volumes were acquired, it is important to know if ventricular-lumbar concentration gradients exist. This has only been addressed for a few biogenic amines, and almost exclusively in neurologically unwell patients due to the burden of a lumbar puncture (necessary to obtain CSF). The aim of our study was to determine if concentration gradients exist for routinely measured CSF constituents and biogenic amines in neurologically healthy patients. We applied a novel ultrasensitive liquid chromatography mass spectrometry (LC–MS/MS) method for the simultaneous quantification of multiple monoamines, precursors and metabolites in CSF and plasma. Methods: CSF and blood samples were collected from twenty neurologically healthy patients undergoing spinal anaesthesia. Ten mL of lumbar CSF was collected in five consecutive two mL fractions. We determined leucocyte and erythrocyte counts, glucose, albumin and protein concentrations and quantified monoamines, precursors and metabolites on each of the fractions using LC–MS/MS. Results: In twenty patients (60% male; median age: 46 years), dopamine, DOPAC, 3-MT, HVA, noradrenaline, normetanephrine and 5-HIAA concentrations increased from the first to the last CSF fraction (all p < 0.001). CSF adrenaline concentrations were below the detection limit, whereas serotonin measurements were regarded as unreliable. Albumin and total protein levels decreased significantly across CSF fractions. Conclusions: A ventricular-lumbar CSF concentration gradient existed for most of the investigated analytes. This is a novel finding for dopamine, noradrenaline, 3-MT and normetanephrine. These results contribute to the understanding of the neurobiology and underline the importance of standardized procedures for CSF handling to allow comparisons between studies

Prostate cancer diagnosis by optical coherence tomography: First results from a needle based optical platform for tissue sampling

The diagnostic accuracy of Optical Coherence Tomography (OCT) based optical attenuation coefficient analysis is assessed for the detection of prostate cancer. Needle-based OCT-measurements were performed on the prostate specimens. Attenuation coefficients were determined by an earlier described in-house developed software package. The mean attenuation coefficients (benign OCT data; malignant OCT data; p-value Mann-Whitney U test) were: (3.56 mm(-1) ; 3.85 mm(-1) ; p < 0.0001) for all patients combined. The area under the ROC curve was 0.64. In order to circumvent the effect of histopathology mismatching, we performed a sub-analysis on only OCT data in which tumor was visible in two subsequent histopathological prostate slices. This analysis could be performed in 3 patients. The mean attenuation coefficients (benign OCT data; malignant OCT data; p-value Mann-Whitney U test) were: (3.23 mm(-1) ; 4.11 mm(-1) ; p < 0.0001) for all patients grouped together. The area under the ROC curve was 0.89. Functional OCT of the prostate has shown to differentiate between cancer and healthy prostate tissue. The optical attenuation coefficient in malignant tissue was significantly higher in malignant tissue compared to benign prostate tissue. Further studies are required to validate these initial results in a larger group of patients with a more tailored histopathology matching protoco