New chemical biopsy tool for spatially resolved profiling of human brain tissue in vivo

Abstract

It is extremely challenging to perform chemical analyses of the brain, particularly in humans, due to the restricted access to this organ. Imaging techniques are the primary approach used in clinical practice, but they only provide limited information about brain chemistry. Solid-phase microextraction (SPME) has been presented recently as a chemical biopsy tool for the study of animal brains. The current work demonstrates for the first time the use of SPME for the spatially resolved sampling of the human brain in vivo. Specially designed multi-probe sampling device was used to simultaneously extract metabolites from the white and grey matter of patients undergoing brain tumor biopsies. Samples were collected by inserting the probes along the planned trajectory of the biopsy needle prior to the procedure, which was followed by metabolomic and lipidomic analyses. The results revealed that studied brain structures were predominantly composed of lipids, while the concentration and diversity of detected metabolites was higher in white than in grey matter. Although the small number of participants in this research precluded conclusions of a biological nature, the results highlight the advantages of the proposed SPME approach, as well as disadvantages that should be addressed in future studies.

Metabolomic Phenotyping of Gliomas: What Can We Get with Simplified Protocol for Intact Tissue Analysis?

“…Therefore, it needs to be emphasized that there are ongoing parallel studies complementing the investigations on device/protocol modifications and instrumental analysis following on-site sampling to provide the medical practitioners with ready-to-use solution for rapid determination of target biomarkers. In recent work, a device which on one hand enables to shorten the extraction process to 4 min and to perform extraction from two brain locations simultaneously on the other was presented [ 58 ]. This strategy is intended to be used eventually for the analysis of brain tumors and healthy brain tissue in the given patient at the same time.…”

Profiling of Carnitine Shuttle System Intermediates in Gliomas Using Solid-Phase Microextraction (SPME)

“…In the future, it may be possible to obtain more detailed information about the biology of brain tumors by combining in situ SPME sampling coupled to LC-MS/MS with histological, immunochemical, or genetic platforms. Moreover, in the view of the recent work which demonstrated that SPME enables spatially resolved analysis of the living human brain [35], it can be expected that one of the future directions in carnitine analysis will be their simultaneous profiling in cancerous and normal tissue.…”

Investigating the Potential Use of Chemical Biopsy Devices to Characterize Brain Tumor Lipidomes

“…Alternatively, chemical biopsy tools such as miniaturized SPME probes enable dot-sampling, which was developed by Vasiljevic et al [37] and can be employed to sample small target areas. Another tool that has been applied to obtain spatially resolved data is an SPME device consisting of four fibers, which was successfully deployed to extract analytes from grey and white matter during neurosurgical procedures [21]. In addition, the ability of a single fiber to capture the average lipidome composition of an entire lesion is valuable with respect to the future use of this technology in in vivo studies.…”

“…The obtained results were then filtered using the following parameters: for extraction quality control (QC), an area coefficient of variation (CV) below 30 and not equal to 0; the QC: extraction blank area ratio above 20; and a peak quality factor above 0.85 for at least one of the studied groups. Further information relating to these search parameters has been detailed in a previous work [21]. After filtering the results, the peak areas for all detected tentative lipids were normalized on the summary peak area of the probe, followed by the application of statistical analysis.…”

“…However, such analytical methods still require tissue to be excised and cut into thin slices. In contrast, solid-phase microextraction (SPME) enables tissue analysis without any pre-treatment, which has led to its use in a wide range of areas including neuroscience, pharmacotherapy, and organ transplantation [11][12][13][14][15][16][17][18][19][20][21].…”