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      The role of cerebral blood flow gradient in peritumoral edema for differentiation of glioblastomas from solitary metastatic lesions

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          Abstract

          Objective

          Differentiation of glioblastomas from solitary brain metastases using conventional MRI remains an important unsolved problem. In this study, we introduced the conception of the cerebral blood flow (CBF) gradient in peritumoral edema—the difference in CBF values from the proximity of the enhancing tumor to the normal-appearing white matter, and investigated the contribution of perfusion metrics on the discrimination of glioblastoma from a metastatic lesion.

          Materials and Methods

          Fifty-two consecutive patients with glioblastoma or a solitary metastatic lesion underwent three-dimensional arterial spin labeling (3D-ASL) before surgical resection. The CBF values were measured in the peritumoral edema (near: G1; Intermediate: G2; Far: G3). The CBF gradient was calculated as the subtractions CBF G1 –CBF G3, CBF G1 – CBF G2 and CBF G2 – CBF G3. A receiver operating characteristic (ROC) curve analysis was used to seek for the best cutoff value permitting discrimination between these two tumors.

          Results

          The absolute/related CBF values and the CBF gradient in the peritumoral regions of glioblastomas were significantly higher than those in metastases( P < 0.038). ROC curve analysis reveals, a cutoff value of 1.92 ml/100g for the CBF gradient of CBF G1 –CBF G3 generated the best combination of sensitivity (92.86%) and specificity (100.00%) for distinguishing between a glioblastoma and metastasis.

          Conclusion

          The CBF gradient in peritumoral edema appears to be a more promising ASL perfusion metrics in differentiating high grade glioma from a solitary metastasis.

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          Most cited references36

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          Diffuse glioma growth: a guerilla war

          In contrast to almost all other brain tumors, diffuse gliomas infiltrate extensively in the neuropil. This growth pattern is a major factor in therapeutic failure. Diffuse infiltrative glioma cells show some similarities with guerilla warriors. Histopathologically, the tumor cells tend to invade individually or in small groups in between the dense network of neuronal and glial cell processes. Meanwhile, in large areas of diffuse gliomas the tumor cells abuse pre-existent “supply lines” for oxygen and nutrients rather than constructing their own. Radiological visualization of the invasive front of diffuse gliomas is difficult. Although the knowledge about migration of (tumor)cells is rapidly increasing, the exact molecular mechanisms underlying infiltration of glioma cells in the neuropil have not yet been elucidated. As the efficacy of conventional methods to fight diffuse infiltrative glioma cells is limited, a more targeted (“search & destroy”) tactic may be needed for these tumors. Hopefully, the study of original human glioma tissue and of genotypically and phenotypically relevant glioma models will soon provide information about the Achilles heel of diffuse infiltrative glioma cells that can be used for more effective therapeutic strategies.
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            Test-retest reliability of arterial spin labeling with common labeling strategies.

            To compare the test-retest reproducibility of three variants of arterial spin labeling (ASL): pseudo-continuous (pCASL), pulsed (PASL) and continuous (CASL). Twelve healthy subjects were scanned on a 3.0T scanner with PASL, CASL, and pCASL. Scans were repeated within-session, after 1 hour, and after 1 week to assess reproducibility at different scan intervals. Comparison of within-subject coefficients of variation (wsCV) demonstrated high within-session reproducibility (ie, low wsCV) for CASL-based methods (gray matter [GM] wsCV for pCASL: 3.5% ± 0.02%, CASL: 4.1% ± 0.07%) compared to PASL (wsCV: 7.5% ± 0.06%), due to the higher signal-to-noise ratio (SNR) associated with continuous labeling, evident in the 20% gain in temporal SNR and 58% gain in raw SNR for pCASL relative to PASL. At the 1-week scan interval, comparable reproducibility between PASL (GM wsCV 9.2% ± 0.12%) and pCASL (GM wsCV 8.5% ± 0.14%) was observed, indicating the dominance of physiological fluctuations. Although all three approaches are capable of measuring cerebral blood flow within a few minutes of scanning, the high precision and SNR of pCASL, with its insensitivity to vessel geometry, make it an appealing method for future ASL application studies. Copyright © 2011 Wiley-Liss, Inc.
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              A mathematical model of glioblastoma tumor spheroid invasion in a three-dimensional in vitro experiment.

              Glioblastoma, the most malignant form of brain cancer, is responsible for 23% of primary brain tumors and has extremely poor outcome. Confounding the clinical management of glioblastomas is the extreme local invasiveness of these cancer cells. The mechanisms that govern invasion are poorly understood. To gain insight into glioblastoma invasion, we conducted experiments on the patterns of growth and dispersion of U87 glioblastoma tumor spheroids in a three-dimensional collagen gel. We studied two different cell lines, one with a mutation to the EGFR (U87DeltaEGFR) that is associated with increased malignancy, and one with an endogenous (wild-type) receptor (U87WT). We developed a continuum mathematical model of the dispersion behaviors with the aim of identifying and characterizing discrete cellular mechanisms underlying invasive cell motility. The mathematical model quantitatively reproduces the experimental data, and indicates that the U87WT invasive cells have a stronger directional motility bias away from the spheroid center as well as a faster rate of cell shedding compared to the U87DeltaEGFR cells. The model suggests that differences in tumor cell dispersion may be due to differences in the chemical factors produced by cells, differences in how the two cell lines remodel the gel, or different cell-cell adhesion characteristics.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                18 October 2016
                15 September 2016
                : 7
                : 42
                : 69051-69059
                Affiliations
                1 Department of Radiology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, China
                2 Department of Radiology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China
                Author notes
                Correspondence to: Yunjing Xue, xueyunjing@ 123456126.com
                Article
                12053
                10.18632/oncotarget.12053
                5356611
                27655705
                c065349d-7348-4d3f-9c11-33884f9166eb
                Copyright: © 2016 Lin et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 May 2016
                : 2 September 2016
                Categories
                Clinical Research Paper

                Oncology & Radiotherapy
                three-dimensional arterial spin labeling,cerebral blood flow,perfusion,glioblastoma,metastasis

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