Hypoxia upregulates aldehyde dehydrogenase isoform 1 (ALDH1) expression and induces functional stem cell characteristics in human glioblastoma cells.

Aldehyde dehydrogenase 1 (ALDH1) has been used to isolate tumorigenic stem-like cells in a large number of tumors, including glioblastoma multiforme (GBM). We recently showed that human glioblastoma cells with high ALDH1 (ALDH1(high)) activity contain stem-cell-like characteristics. In the study reported here, we isolated established and primary human glioblastoma cells based on their ALDH1 expression. When tested for asymmetric division, only cells with ALDH1(high) expression were able to restore heterogeneous populations after a few days, whereas cells with ALDH1(low) levels could not. Most interestingly, the capacity of cells with ALDH1(low) levels to divide asymmetrically into cells with either ALDH1(high) or ALDH1(low) expression could be restored after exposure to hypoxic culture conditions. Consequently, we found neurosphere formation reinstated in posthypoxic, formerly ALDH1(low), cells. The direct involvement of ALDH1 could be confirmed by ALDH1 small hairpin ribonucleic acid (shRNA) knockdown, suggesting ALDH1 as an intracellular marker for the identification and isolation of stem-like glioblastoma cells. In summary, we show that ALDH1 expression correlates well with asymmetric division capacity and tumor sphere formation. Furthermore, we demonstrated that hypoxic culture conditions induce and/or upregulate ALDH1 expression in established and primary GBM cell lines.

Multimodal imaging in cerebral gliomas and its neuropathological correlation.

INTRODUCTION: Concerning the preoperative clinical diagnostic work-up of glioma patients, tumor heterogeneity challenges the oncological therapy. The current study assesses the performance of a multimodal imaging approach to differentiate between areas in malignant gliomas and to investigate the extent to which such a combinatorial imaging approach might predict the underlying histology. METHODS: Prior to surgical resection, patients harboring intracranial gliomas underwent MRIs (MR-S, PWI) and (18)F-FET-PETs. Intratumoral and peritumoral biopsy targets were defined, by MRI only, by FET-PET only, and by MRI and FET-PET combined, and biopsied prior to surgical resection and which then received separate histopathological examinations. RESULTS: In total, 38 tissue samples were acquired (seven glioblastomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma, one diffuse astrocytoma, and one oligoastrocytoma) and underwent histopathological analysis. The highest mean values of Mib1 and CD31 were found in the target point "T' defined by MRI and FET-PET combined. A significant correlation between NAA/Cr and PET tracer uptake (-0.845, p<0.05) as well as Cho/Cr ratio and cell density (0.742, p<0.05) and NAA/Cr ratio and MIB-1 (-0761, p<0.05) was disclosed for this target point, though not for target points defined by MRI and FET-PET alone. CONCLUSION: Multimodal-imaging-guided stereotactic biopsy correlated more with histological malignancy indices, such as cell density and MIB-1 labeling, than targets that were based solely on the highest amino acid uptake or contrast enhancement on MRI. The results of our study indicate that a combined PET-MR multimodal imaging approach bears potential benefits in detecting glioma heterogeneity.

Operation-microscope-mounted touch display tablet computer for intraoperative imaging visualization.

OBJECTIVE: The authors have developed a novel sterile draped touch display solution for convenient intraoperative access to imaging data. This study describes the technology and clinical experience of the system. METHODS: We developed a flexible, mounted touch display solution (Apple iPad) that allows fixation of the display on the operation microscope and fine adjustments during surgery when the microscope is moved. We compared this setup with a conventional wall-mounted flat-panel and a mobile display stand in illustrative cases of vestibular schwannoma. RESULTS: The surgeon was able to employ the system without the need to leave the operation field or the need for external assistance while referring to imaging data. Commanding through imaging data with sterile gloves on the touch display was more convenient, more precise, and faster compared with other modalities. CONCLUSION: The operation-microscope-mounted touch display provides useful assistance for intraoperative imaging visualization in neurosurgical procedures.

Hybrid system for simultaneous fluorescence and x-ray computed tomography.

A hybrid imaging system for simultaneous fluorescence tomography and X-ray computed tomography (XCT) of small animals has been developed and presented. The system capitalizes on the imaging power of a 360 ( degrees )-projection free-space fluorescence tomography system, implemented within a microcomputed tomography scanner. Image acquisition is based on techniques that automatically adjust a series of imaging parameters to offer a high dynamic range dataset. Image segmentation further allows the incorporation of structural priors in the optical reconstruction problem to improve the imaging performance. The functional system characteristics are showcased, and images from a brain imaging study are shown, which are reconstructed using XCT-derived priors into the optical forward problem.