Intraoperative optical imaging of metabolic changes after direct cortical stimulation – a clinical tool for guidance during tumor resection?

2018 ◽  
Vol 63 (5) ◽  
pp. 587-594
Author(s):  
Martin Oelschlägel ◽  
Tobias Meyer ◽  
Gabriele Schackert ◽  
Matthias Kirsch ◽  
Stephan B. Sobottka ◽  
...  
Keyword(s):  
Optical Imaging ◽  
Brain Tissue ◽  
Tumor Tissue ◽  
Tumor Resection ◽  
Cortical Stimulation ◽  
Normal Brain ◽  
Clinical Tool ◽  
Novel Approach ◽  
Intact Brain ◽  
Characteristic Features

AbstractBrain tumor resection is even today one of the most challenging disciplines in neurosurgery. The current state of the art for the identification of tumor tissue during the surgical procedure comprises a wide variety of different tools, each with its own limitations and drawbacks. In this paper, we present a novel approach, the use of optical imaging in connection with direct electrical cortical stimulation (DCS), for identification of impaired tumor tissue and functional intact normal brain tissue under intraoperative conditions. Measurements with an optical imaging setup were performed as a proof of concept on three patients who underwent tumor resection of superficial gliomas. Direct electrical stimulations were applied on tumor tissue and surrounding brain tissue in each patient and characteristic features from the observed changes in the optical properties were compared between the different groups. The results reveal that in all patients a differentiation between non-functional tumor tissue and functional intact brain tissue was possible, and the technique might be a useful clinical tool in the future.

scholarly journals Potential improvement of survival statistics for glioblastoma multiforme (WHO IV)

2019 ◽  
Vol 10 ◽  
pp. 123
Author(s):  
Harry S. Goldsmith
Keyword(s):  
Glioblastoma Multiforme ◽  
Blood Vessels ◽  
Brain Tissue ◽  
Day Treatment ◽  
Tumor Resection ◽  
Current Treatment ◽  
Chemotherapeutic Agents ◽  
Normal Brain ◽  
Malignant Cells ◽  
Potential Improvement

The present-day treatment of a glioblastoma multiforme IV (glioblast) is by surgery, radiation, and chemotherapy. Unfortunately, the current treatment has not significantly improved the survival statistics of this tumor. There are now two relatively new surgical procedures that may improve the survival statistics of this malignancy. One of these procedures is the intraoperative use of the drug 5-aminovolumic acid (ALA), which fluoresces a red color in malignant brain tissue that is not observed in normal brain tissue. This allows a neurosurgeon to distinguish brain tissue infiltrated by malignant cells, thus allowing a more complete resection of the tumor. Another procedure that has the potential to improve the survival statistics of glioblasts is the use of the omentum. Direct placement of the omentum on a brain infiltrated by malignant cells would allow omental blood vessels, known to be completely clear of endothelial cells, to penetrate directly into the underlying brain. The blood flow through omental blood vessels could be expected to carry chemotherapeutic agents throughout the involved brain, thereby totally bypassing the blood–brain barrier. Combining a tumor resection using 5-ALA and placing the omentum on the brain may prove instrumental in improving the survival statistics of patients suffering from a glioblast.

Observations of intracranial neoplasms treated with gamma knife radiosurgery

2002 ◽  
Vol 97 ◽  
pp. 623-626 ◽  
Author(s):  
György T. Szeifert ◽  
Nicolas Massager ◽  
Daniel DeVriendt ◽  
Philippe David ◽  
Françoise De Smedt ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Brain Tissue ◽  
Gamma Knife ◽  
Tumor Tissue ◽  
Gamma Knife Radiosurgery ◽  
Normal Brain ◽  
Vascular Endothelial ◽  
Normal Brain Tissue ◽  
Content Type ◽  
Fine Print

Object. The purpose of this study was to compare histopathological changes with imaging findings in different tumors after gamma knife radiosurgery (GKS). Methods. Five patients of a series of 220 treated with GKS underwent craniotomy for tumor removal 3 to 12 months after radiosurgery. There were two patients with multiple cerebral metastases, one with vestibular schwannoma, one with malignant glioma, and one with meningioma. A portion of normal brain tissue outside the prescription dose volume was acquired wherever possible to facilitate examination of the effects of radiosurgery. Histopathological and immunohistochemical investigations were performed. In addition to the routine hematoxylin and eosin and Mallory trichrome stains, immunohistochemical reactions were also performed for Factor VIII—associated antigen (FVIII) and CD34 antigen to study vascular endothelial effects of the irradiation. Endothelial cells of vessels in the normal brain tissue covering the tumor, outside of the prescription isodose volume, expressed marked CD34 and FVIII positivity. In the irradiated targeted tumor tissue samples, however, both reactions decreased remarkably. Conclusions. The results of the present immunohistochemical study provide support to the experimental hypothesis that vascular endothelial cells are the principal targets of single high-dose irradiation. The loss of central contrast enhancement of tumor tissue following radiosurgery might be consequence of the vascular damage.

scholarly journals Protein Kinase A Distribution in Meningioma

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1686 ◽  
Author(s):  
Caretta ◽  
Denaro ◽  
D’Avella ◽  
Mucignat-Caretta
Keyword(s):  
Brain Tissue ◽  
Catalytic Subunit ◽  
Therapeutic Interventions ◽  
Normal Brain ◽  
Local Concentration ◽  
Correlation Pattern ◽  
Catalytic Subunits ◽  
Tissue Specimens ◽  
Pka Catalytic Subunit

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions.

scholarly journals Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariano Guardia Clausi ◽  
Alexander M. Stessin ◽  
Zirun Zhao ◽  
Stella E. Tsirka ◽  
Samuel Ryu
Keyword(s):  
Brain Tissue ◽  
Cranial Irradiation ◽  
Subcortical White Matter ◽  
Glioma Cell Line ◽  
Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Long Term Effects ◽  
Normal Brain Tissue ◽  
Molecule Inhibitor

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

Quantitative Measurements of Regional Glucose Utilization and Rate of Valine Incorporation into Proteins by Double-Tracer Autoradiography in the Rat Brain Tumor Model

1989 ◽  
Vol 9 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Michihiro Kirikae ◽  
Mirko Diksic ◽  
Y. Lucas Yamamoto
Keyword(s):  
Protein Synthesis ◽  
Brain Tumor ◽  
Rat Brain ◽  
Brain Tissue ◽  
Glucose Utilization ◽  
Tumor Model ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Rat Brain Tumor ◽  
Brain Tumor Model

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: “kinetic” (quantitation done using an operational equation and the average brain rate coefficients) and “washed slices” (unbound labeled valine removed by washing brain slices in 10% thrichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography.

PET Study of Methionine Accumulation in Glioma and Normal Brain Tissue

1987 ◽  
Vol 11 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Mats Bergström ◽  
Kaj Ericson ◽  
Lars Hagenfeldt ◽  
Mikael Mosskin ◽  
Hans von Holst ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Normal Brain ◽  
Normal Brain Tissue

Quantitative Analysis of Mobile Proteins in Normal Brain Tissue by Amide Proton Transfer Imaging

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Kazuaki Sugawara ◽  
Tosiaki Miyati ◽  
Ryo Ueda ◽  
Daisuke Yoshimaru ◽  
Masanobu Nakamura ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Proton Transfer ◽  
Brain Tissue ◽  
Amide Proton ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Amide Proton Transfer ◽  
Amide Proton Transfer Imaging

Abstract T P234: Multiparametric Assessment of Longitudinal Changes in Tissue Microstructure in Normal and Abnormal Brain Tissue in Patients with Small Vessel Disease

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Maria D Valdes-Hernandez ◽  
Paul A Armitage ◽  
Eleni Sakka ◽  
Susana Munoz Maniega ◽  
Natalie A Royle ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Tissue ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Tissue Loss ◽  
Minor Stroke ◽  
Normal Brain ◽  
Limited Information ◽  
Time Points

Background: Volume measures of normal brain tissue and white matter hyperintensities (WMH) between two time points gives limited information about the complex dynamics of tissue change. We evaluated two quantitative parameters that characterise the microstructure of normal-appearing white matter (NAWM), deep grey matter (DGM) and WMH on brain images obtained at presentation with minor stroke and at 1 year to investigate the microstructural changes. Methods: From 182 brain MRI datasets of patients with minor stroke obtained at baseline and 1 year, we extracted the WMH, DGM and NAWM, and separated WMH into less-intense and intense WMH, using validated semi-automatic methods and validated criteria. We registered the binary structural masks to diffusion space and performed a voxel-wise subtraction of the combined masks at both time points. Then we measured fractional anisotropy (FA) and mean diffusivity (MD)(valuex10 -9 m 2 /s) in each tissue mask at baseline and 1 year. Results: WMH volume median increase was 1.4ml (IQR 6.98) mainly due to changes in less-intense WMH: 0.94ml (7.13). WMH that were visible at both time points, ie damage that remained after a year, had the lowest FA= 0.21(0.06) and highest MD=1.05(0.12) at baseline, and were mainly intense WMH at baseline (FA=0.12(0.03), MD=1.55(0.27)). WMH seen only at follow-up, ie that were NAWM at baseline, had the highest FA=0.30(0.06) and lowest MD=0.85 (0.06) at baseline. WMH that were observed only at baseline had intermediate FA=0.26(0.08) and MD=0.90(0.10). NAWM FA=0.26(0.03), MD=0.78(0.04) and DGM FA=0.23(0.03), MD=0.79(0.06) did not change between time points. Conclusions: WMH at baseline can partially evolve to normal-appearing tissues, remain or precede tissue loss. Differentiation between severe and subtle damage and spatial analysis are necessary to characterise the dynamic of WMH evolution.

scholarly journals Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients

2018 ◽  
Vol 28 (1) ◽  
pp. 56-62
Author(s):  
Cahit Kural ◽  
Arzu Kaya Kocdogan ◽  
Gulcin Güler Şimşek ◽  
Serpil Oğuztüzün ◽  
Pınar Kaygın ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Brain Tissue ◽  
Pituitary Adenomas ◽  
Normal Brain ◽  
Cytochrome P450 Enzyme ◽  
Intracranial Tumors ◽  
Glutathione S Transferase ◽  
Normal Brain Tissue ◽  
Tissue Samples ◽  
P450 Enzyme

Objective: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. Subjects and Methods: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016–2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. Results: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP­1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. Conclusion: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes.

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