The Role of Fibroblast Activation Protein in Glioblastoma and Gliosarcoma: A Comparison of Tissue, 68Ga-FAPI-46 PET Data, and Survival Data.

Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68Ga-FAP inhibitor (FAPI)-46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0-3, with higher values indicating stronger expression). Additionally, 68Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue (P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUVmean and SUVpeak of 68Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUVmean and SUVpeak in 68Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis.

Label-free detection of brain tumors in a 9L gliosarcoma rat model using stimulated Raman scattering-spectroscopic optical coherence tomography.

SIGNIFICANCE: In neurosurgery, it is essential to differentiate between tumor and healthy brain regions to maximize tumor resection while minimizing damage to vital healthy brain tissue. However, conventional intraoperative imaging tools used to guide neurosurgery are often unable to distinguish tumor margins, particularly in infiltrative tumor regions and low-grade gliomas. AIM: The aim of this work is to assess the feasibility of a label-free molecular imaging tool called stimulated Raman scattering-spectroscopic optical coherence tomography (SRS-SOCT) to differentiate between healthy brain tissue and tumor based on (1) structural biomarkers derived from the decay rate of signals as a function of depth and (2) molecular biomarkers based on relative differences in lipid and protein composition extracted from the SRS signals. APPROACH: SRS-SOCT combines the molecular sensitivity of SRS (based on vibrational spectroscopy) with the spatial and spectral multiplexing capabilities of SOCT to enable fast, spatially and spectrally resolved molecular imaging. SRS-SOCT is applied to image a 9L gliosarcoma rat tumor model, a well-characterized model that recapitulates human high-grade gliomas, including high proliferative capability, high vascularization, and infiltration at the margin. Structural and biochemical signatures acquired from SRS-SOCT are extracted to identify healthy and tumor tissues. RESULTS: Data show that SRS-SOCT provides light-scattering-based signatures that correlate with the presence of tumors, similar to conventional OCT. Further, nonlinear phase changes from the SRS interaction, as measured with SRS-SOCT, provide an additional measure to clearly separate tumor tissue from healthy brain regions. We also show that the nonlinear phase signals in SRS-SOCT provide a signal-to-noise advantage over the nonlinear amplitude signals for identifying tumors. CONCLUSIONS: SRS-SOCT can distinguish both spatial and spectral features that identify tumor regions in the 9L gliosarcoma rat model. This tool provides fast, label-free, nondestructive, and spatially resolved molecular information that, with future development, can potentially assist in identifying tumor margins in neurosurgery.

Do gliosarcomas have distinct imaging features on routine MRI?

PURPOSE: The aim of this study was the development and external validation of a logistic regression model to differentiate gliosarcoma (GSC) and glioblastoma multiforme (GBM) on standard MR imaging. METHODS: A univariate and multivariate analysis was carried out of a logistic regression model to discriminate patients histologically diagnosed with primary GSC and an age and sex-matched group of patients with primary GBM on presurgical MRI with external validation. RESULTS: In total, 56 patients with GSC and 56 patients with GBM were included. Evidence of haemorrhage suggested the diagnosis of GSC, whereas cystic components and pial as well as ependymal invasion were more commonly observed in GBM patients. The logistic regression model yielded a mean area under the curve (AUC) of 0.919 on the training dataset and of 0.746 on the validation dataset. The accuracy in the validation dataset was 0.67 with a sensitivity of 0.85 and a specificity of 0.5. CONCLUSIONS: Although some imaging criteria suggest the diagnosis of GSC or GBM, differentiation between these two tumour entities on standard MRI alone is not feasible.

The clinical, radiological, and immunohistochemical characteristics and outcomes of primary intracranial gliosarcoma: a retrospective single-centre study.

Primary intracranial gliosarcoma is a rare malignant brain tumour, and the most effective treatment for gliosarcoma remains unclear. This study aimed to identify risk factors for progression-free survival (PFS) and overall survival (OS) in these cases. This retrospective single-centre study evaluated 103 patients (median age, 51 years; 67 men [65%]) with primary intracranial gliosarcoma between 2006 and 2017. Treatments included surgery (GTR, 63 patients; STR, 39 patients; biopsy, 1 patient), radiotherapy (adjuvant, 76 patients; exclusive treatment, 1 patient), and chemotherapy (adjuvant temozolomide, 52 patients; adjuvant nimustine/teniposide, 19 patients; adjuvant bevacizumab, 1 patient; exclusive nimustine/teniposide treatment, 1 patient). The median OS was 13.3 months, and the median PFS was 9.1 months. In the multivariate analyses, the poor prognostic factors were ependymal lining enhancement of the lateral ventricle (PFS, HR 2.406, p = 0.005; OS, HR 2.946, p = 0.009) and enhancement in the motor functional cortex (PFS, HR 2.892, p = 0.002; OS, HR 2.639, p = 0.009). Good OS was predicted by adjuvant radiotherapy alone (HR 0.071, p < 0.001), adjuvant temozolomide-based chemotherapy alone (HR 0.063, p = 0.005), adjuvant temozolomide-based chemotherapy with concurrent radiotherapy (HR 0.056, p < 0.001), and salvage surgery at recurrence (HR 0.449, p = 0.031). The present study revealed that, in patients with primary intracranial gliosarcoma, enhancement in the functional motor cortex and ependymal lining enhancement of the lateral ventricle were both poor prognostic factors. Survival was optimized in cases treated using maximal safe resection followed by adjuvant temozolomide-based chemotherapy with concurrent radiotherapy. Furthermore, salvage surgery provided meaningful therapeutic benefits for recurrent gliosarcoma.

Innovative high-resolution microCT imaging of animal brain vasculature.

Analysis of the angioarchitecture and quantification of the conduit vessels and microvasculature is of paramount importance for understanding the physiological and pathological processes within the central nervous system (CNS). Most of the available in vivo imaging methods lack penetration depth and/or resolution. Some ex vivo methods may provide better resolution, but are mainly destructive, as they are designed for imaging the CNS tissues after their removal from the skull or vertebral column. The removal procedure inevitably alters the in situ relations of the investigated structures and damages the dura mater and leptomeninges. µAngiofil, a polymer-based contrast agent, permits a qualitatively novel postmortem microangio-computed tomography (microangioCT) approach with excellent resolution and, therefore, visualization of the smallest brain capillaries. The datasets obtained empower a rather straightforward quantitative analysis of the vascular tree, including the microvasculature. The µAngiofil has an excellent filling capacity as well as a radio-opacity higher than the one of bone tissue, which allows imaging the cerebral microvasculature even within the intact skull or vertebral column. This permits in situ visualization and thus investigation of the dura mater and leptomeningeal layers as well as their blood supply in their original geometry. Moreover, the methodology introduced here permits correlative approaches, i.e., microangioCT followed by classical histology, immunohistochemistry and even electron microscopy. The experimental approach presented here makes use of common desktop microCT scanners, rendering it a promising everyday tool for the evaluation of the (micro)vasculature of the central nervous system in preclinical and basic research.

A practical method for multimodal registration and assessment of whole-brain disease burden using PET, MRI, and optical imaging.

Many neurological diseases present with substantial genetic and phenotypic heterogeneity, making assessment of these diseases challenging. This has led to ineffective treatments, significant morbidity, and high mortality rates for patients with neurological diseases, including brain cancers and neurodegenerative disorders. Improved understanding of this heterogeneity is necessary if more effective treatments are to be developed. We describe a new method to measure phenotypic heterogeneity across the whole rodent brain at multiple spatial scales. The method involves co-registration and localized comparison of in vivo radiologic images (e.g. MRI, PET) with ex vivo optical reporter images (e.g. labeled cells, molecular targets, microvasculature) of optically cleared tissue slices. Ex vivo fluorescent images of optically cleared pathology slices are acquired with a preclinical in vivo optical imaging system across the entire rodent brain in under five minutes, making this methodology practical and feasible for most preclinical imaging labs. The methodology is applied in various examples demonstrating how it might be used to cross-validate and compare in vivo radiologic imaging with ex vivo optical imaging techniques for assessing hypoxia, microvasculature, and tumor growth.

Gliosarcomas: magnetic resonance imaging findings.

BACKGROUND: Central nervous system (CNS) gliosarcoma (GSM) is a rare primary neoplasm characterized by the presence of glial and sarcomatous components. OBJECTIVE: In this report, we describe the clinical and neuroimaging aspects of three cases of GSM and correlate these aspects with pathological findings. We also provide a brief review of relevant literature. METHODS: Three patients were evaluated with magnetic resonance imaging (MRI), and biopsies confirmed the diagnosis of primary GSM, without previous radiotherapy. RESULTS: The analysis of conventional sequences (T1, T1 after contrast injection, T2, Fluid attenuation inversion recovery, SWI and DWI/ADC map) and advanced (proton 1H MR spectroscopy and perfusion) revealed an irregular, necrotic aspect of the lesion, peritumoral edema/infiltration and isointensity of the solid component on a T2-weighted image. These features were associated with irregular and peripheral contrast enhancement, lipid and lactate peaks, increased choline and creatine levels in proton spectroscopy, increased relative cerebral blood volume (rCBV) in perfusion, multifocality and drop metastasis in one of the cases. CONCLUSION: These findings are discussed in relation to the general characteristics of GSM reported in the literature.

Gliosarcomas: magnetic resonance imaging findings / Gliossarcomas: achados de ressonância magnética

Abstract Background: Central nervous system (CNS) gliosarcoma (GSM) is a rare primary neoplasm characterized by the presence of glial and sarcomatous components. Objective: In this report, we describe the clinical and neuroimaging aspects of three cases of GSM and correlate these aspects with pathological findings. We also provide a brief review of relevant literature. Methods: Three patients were evaluated with magnetic resonance imaging (MRI), and biopsies confirmed the diagnosis of primary GSM, without previous radiotherapy. Results: The analysis of conventional sequences (T1, T1 after contrast injection, T2, Fluid attenuation inversion recovery, SWI and DWI/ADC map) and advanced (proton 1H MR spectroscopy and perfusion) revealed an irregular, necrotic aspect of the lesion, peritumoral edema/infiltration and isointensity of the solid component on a T2-weighted image. These features were associated with irregular and peripheral contrast enhancement, lipid and lactate peaks, increased choline and creatine levels in proton spectroscopy, increased relative cerebral blood volume (rCBV) in perfusion, multifocality and drop metastasis in one of the cases. Conclusion: These findings are discussed in relation to the general characteristics of GSM reported in the literature.

Resumo Introdução: O gliossarcoma (GSM) do sistema nervoso central (SNC) é uma neoplasia primária rara, caracterizada pela presença de componentes gliais e sarcomatosos. Objetivo: Nosso objetivo é descrever os aspectos clínicos e de neuroimagem de três casos com este diagnóstico e correlacioná-los com os achados patológicos. Também foi realizada uma breve revisão da literatura relevante. Métodos: Três pacientes foram avaliados por ressonância magnética (RM), e biópsias confirmaram o diagnóstico de GSM primário, sem radioterapia prévia. Resultados: Foram analisadas as sequências convencionais (T1, T1 após injeção de contraste, T2, FLAIR-fluid attenuation inversion recovery, SWI, DWI/mapa ADC) e as sequências avançadas (espectroscopia de prótons 1H e perfusão), observando-se aspecto necrótico e irregular da lesão, edema/infiltração peritumoral, isointensidade do componente sólido em T2, associada a realce irregular e periférico pelo meio de contraste, pico de lípides e de lactato e aumento dos níveis de colina e creatina na espectroscopia de prótons, aumento do volume sanguíneo cerebral relativo (rCBV) na perfusão, multifocalidade e "drop" mestástase em um dos casos. Conclusão: O presente estudo descreve características do GSM, discutindo as informações na literatura científica, ilustrando algumas particularidades desses tumores.

A rare case of BRAF V600E-mutated epithelioid glioblastoma with a sarcomatous component.

Epithelioid glioblastoma is a rare subtype of glioblastoma, but the coexistence of a sarcomatous component is even rarer. An 80-year-old woman was admitted to our hospital with somnolence. Magnetic resonance imaging revealed a cystic lesion with a solid component in the left temporal-parietal lobe. Histopathological examination of the resected tumor revealed three components; namely, typical glioblastoma, sarcomatous and epithelioid components at a ratio of about 5:3:2. All components were immunohistochemically positive for vimentin and mutated BRAF (V600E) and showed focal expression of glial fibrillary acidic protein and cytokeratin AE1/AE3, but they were negative for isocitrate dehydrogenase 1. Genetic analysis revealed that both the sarcomatous and epithelioid components harbored BRAF T1799A (V600E) mutation and homozygous deletion of cyclin-dependent kinase inhibitor 2A/B. We diagnosed this tumor as epithelial glioblastoma with a sarcomatous component. Our results indicate that even when the epithelial component is not dominant, immunohistochemical and genetic investigation of BRAF mutations is useful for the diagnosis of glioblastoma subtypes. In particular, although the prognosis of epithelial glioblastoma is poor, potentially effective targeted therapies for BRAF V600E-mutated tumors are available.

Identification of Distant Metastases From Recurrent Gliosarcoma Using Whole-Body 18F-FDG PET/CT.

A 51-year-old man presented with recurrent gliosarcoma and increasing cough over the last months. On F-FDG PET/CT, solid lung masses with high F-FDG uptake were present. A biopsy taken from a lung lesion indicated distant metastases from gliosarcoma. Gliosarcoma, a rare malignant central nervous system tumor, presents with extracranial metastases in only less than 10%. As highlighted by this case, F-FDG PET/CT can be used for whole-body staging in patients with metastatic brain tumor. Vice versa, highly F-FDG-avid lung lesions in patients with brain tumors should lead to distant metastases as differential diagnosis despite their rare occurrence.

Gliosarcoma in a Young Filipino Woman: A Case Report and Review of the Literature.

BACKGROUND Gliosarcoma (GS) is a rare variant of glioblastoma (GBM), which is typically seen in patients age 40-60 years and located in the supratentorial region. We present an unusual case of GS in a young patient with an unusual presentation, which eventually led to the finding of this neoplasm. CASE REPORT Our patient was a 38-year-old woman originally from the Philippines who was transferred to our institution with an isolated left foot drop that developed over the course of several months. Subsequent neuroimaging revealed an extensive mixed cystic and solid mass in the posterior mesial right frontal lobe. Subtotal surgical resection revealed a multi-lobed tumor with a malignant glioma-like surface component overlying a smooth, well-encapsulated, avascular, sarcoma-like component. Neuropathologic examination of the resected tumor revealed a biphasic histologic pattern of predominantly sarcomatous components with fewer adjacent-area glial components. Post-operatively, the patient was left with a mild worsening of left leg segmental strength. She was referred to our neurooncologist colleagues for adjuvant treatment options. CONCLUSIONS Our case is unique in that it represents a rare neoplasm in a patient whose demographics are atypical for this type of tumor, as well as the unusual presentation of isolated foot drop.

Chemical exchange saturation transfer (CEST) signal intensity at 7T MRI of WHO IV° gliomas is dependent on the anatomic location.

BACKGROUND: Chemical exchange saturation transfer (CEST) is a novel MRI technique applied to brain tumor patients. PURPOSE: To investigate the anatomic location dependence of CEST MRI obtained at 7T and histopathological/molecular parameters in WHO IV° glioma patients. STUDY TYPE: Analytic prospective study. POPULATION: Twenty-one patients with newly diagnosed WHO IV° gliomas were studied prior to surgery; 11 healthy volunteers were investigated. FIELD STRENGTH/SEQUENCE: Conventional MRI (contrast-enhanced, T2 w and diffusion-weighted imaging) at 3T and T2 w and CEST MRI at 7T was performed for patients and both patients and volunteers. ASSESSMENT: Mean CEST signal intensities (nuclear-Overhauser-enhancement [NOE], amide-proton-transfer [APT], downfield NOE-suppressed APT [dns-APT]), ADC values, and histopathological/molecular parameters were evaluated with regard to hemisphere location and contact with the subventricular zone. CEST signal intensities of cerebral tissue of healthy volunteers were evaluated with regard to hemisphere discrimination. STATISTICAL TESTS: Spearman correlation, Mann-Whitney U-test, Wilcoxon signed-rank-test, Fisher's exact test, and area under the receiver operating curve. RESULTS: Maximum APT and dns-APT signal intensities were significantly different in right vs. left hemisphere gliomas (P = 0.037 and P = 0.007), but not in right vs. left hemisphere cerebral tissue of healthy subjects (P = 0.062-0.859). Mean ADC values were significantly decreased in right vs. left hemisphere gliomas (P = 0.044). Mean NOE signal intensity did not differ significantly between gliomas of either hemisphere (P = 0.820), but in case of subventricular zone contact (P = 0.047). A significant correlation was observed between APT and dns-APT and ADC signal intensities (rs = -0.627, P = 0.004 and rs = -0.534, P = 0.019), but not between NOE and ADC (rs = -0.341, P = 0.154). Histopathological/molecular parameters were not significantly different concerning the tumor location (P = 0.104-1.000, P = 0.286-0.696). DATA CONCLUSION: APT, dns-APT, and ADC were inversely correlated and depended on the gliomas' hemisphere location. NOE showed significant dependence on subventricular zone contact. Location dependency of APT- and NOE-mediated CEST effects should be considered in clinical investigations of CEST MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:777-785.

Gliosarcoma: Neuroimaging and Immunohistochemical Findings.

BACKGROUND AND PURPOSE: Gliosarcoma (GSC) is an intra-axial lesion which often abuts a dural margin and is composed of glial and mesenchymal elements. This lesion is considered a variant of isocitrate dehydrogenase (IDH)-wild type glioblastoma (GBM). The purpose of this study is to evaluate the imaging and molecular features of GSC in a large patient cohort. METHODS: Pathology-proved GSC cases were collected from our quaternary care center spanning the last 16 years and IDH status was documented. Older GSC cases without prior immunohistochemical testing underwent tissue block staining to obtain IDH status. When available, p53, phosphate and tensin (PTEN), MIB-1, EGFR amplification, and MGMT methylation were recorded and imaging findings tabulated. Logistic regression analyses were performed to determine correlation of molecular markers and imaging characteristics. RESULTS: A total of 25 cases were identified (21 de novo, 4 post-treatment). All lesions contacted a dural, pial, or ependymal surface and were negative for an IDH R132H mutation, including postradiation GSC. In total, 16 of 16 cases showed nonamplification of EGFR/CEP7, 2 of 16 demonstrated MGMT methylation, and multiple lesions demonstrated p53 and PTEN mutations. Imaging features included areas of nodular thickening in necrotic lesions which appeared to abut the site of dural contact. There was no significant correlation of molecular markers with imaging characteristics. CONCLUSION: GSC was IDH(-) in all cases, supporting the current understanding of this lesion being a wild-type GBM variant. Additional molecular markers demonstrated no significant correlation with imaging findings in this cohort.

Simultaneous perfusion and permeability assessments using multiband multi-echo EPI (M2-EPI) in brain tumors.

PURPOSE: To study a multiband multi-echo EPI (M2-EPI) sequence for dynamic susceptibility contrast (DSC) perfusion imaging with leakage correction and vascular permeability measurements, and to evaluate the benefits of increased temporal resolution provided by this acquisition strategy on the accuracy of perfusion and permeability estimations. METHODS: A novel M2-EPI sequence was developed, and a pharmacokinetic model accounting for contrast agent extravasation was used to produce perfusion maps and additional vascular permeability maps. The advantage of M2-EPI for DSC perfusion imaging was demonstrated in vivo in 5 patients with brain tumors, and numerical simulations were performed to evaluate the advantage of improved temporal resolution afforded by the technique. RESULTS: In contrast to underestimations of cerebral blood volume (CBV) in tumors using the single-echo acquisition strategy, M2-EPI provided more plausible estimates of CBV. A quantitative evaluation showed higher estimated values of CBV and mean transit time in tumor tissues using M2-EPI (CBV: 3.08 ± 0.78 mL/100 g versus 1.56 ± 1.38 mL/100 g [P = .006]; mean transit time: 4.94 ± 1.17 seconds versus 1.83 ± 2.06 seconds [P = 0.033]). Numerical simulations showed that higher temporal resolution provided by M2-EPI was associated with more accurate estimates of cerebral blood flow, CBV, and permeability parameters. CONCLUSION: The novel M2-EPI acquisition strategy for DSC imaging facilitates leakage-corrected perfusion measurements with additional permeability assessments and more accurate estimates of perfusion/permeability parameters, and may be used as a quantitative tool for the diagnosis, prognosis, and treatment monitoring of brain tumors.

Biological characteristics and outcomes of Gliosarcoma.

Gliosarcoma is a highly aggressive primary brain tumour. It is a relatively rare tumour and comprises of two histological components, glial and sarcomatous. Gliosarcomas carry a poorer prognosis than that of Glioblastoma Multiforme (GBM). The current review highlights important histological and radiological features of gliosarcoma in the light of recent literature, and also touches upon the treatment options and outcomes of various types of gliosarcoma.

Functional and morphological effects of diazepam and midazolam on tumor vasculature in the 9L gliosarcoma brain tumor model using dynamic susceptibility contrast MRI: a comparative study.

Antiangiogenic therapy attenuates tumor growth by reducing vascularization. Diazepam (DZP) and midazolam (MZL) have antiangiogenic properties in human umbilical vein endothelial cells. Thus, we investigated the antiangiogenic activity of DZP and MZL in the rat 9L gliosarcoma brain tumor model. The effect on tumor vasculature was evaluated using dynamic susceptibility contrast magnetic resonance imaging with gradient-echo (GE) and spin-echo (SE) to assess perfusion parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and mean vessel diameter. The GE-normalized CBF (nCBF) in the tumors of untreated controls was significantly lower than that in normal brain tissue, whereas the CBV and MTT were higher. DZP- and MZL-treated rats had higher CBF and lower CBV and MTT values than did untreated controls. The tumor size decreased significantly to 33.5% in DZP-treated rats (P<0.001) and 22.5% in MZL-treated rats (P<0.01) relative to controls. The SE-normalized CBV was lower in DZP-treated (32.9%) and MZL-treated (10.6%) rats compared with controls. The mean vessel diameter decreased significantly by 32.5% in DPZ-treated and by 24.9% in MZL-treated rats compared with controls (P<0.01). The GE and SE nCBF values were higher in DZP-treated (49.9% and 40.1%, respectively) and MZL-treated (41.2% and 32.1%, respectively) rats than in controls. The GE- and SE-normalized MTTs were lower in DZP-treated (48.2% and 59.8%, respectively) and MZL-treated (40.5% and 51.2%, respectively) rats than in controls. Both DZP and MZL had antiangiogenic effects on tumor perfusion and vasculature; however, the antiangiogenic activity of DZP is more promising than that of MZL.

Reproducibility and relative stability in magnetic resonance imaging indices of tumor vascular physiology over a period of 24h in a rat 9L gliosarcoma model.

PURPOSE: The objective was to study temporal changes in tumor vascular physiological indices in a period of 24h in a 9L gliosarcoma rat model. METHODS: Fischer-344 rats (N=14) were orthotopically implanted with 9L cells. At 2weeks post-implantation, they were imaged twice in a 24h interval using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Data-driven model-selection-based analysis was used to segment tumor regions with varying vascular permeability characteristics. The region with the maximum number of estimable parameters of vascular kinetics was chosen for comparison across the two time points. It provided estimates of three parameters for an MR contrast agent (MRCA): i) plasma volume (vp), ii) forward volumetric transfer constant (Ktrans) and interstitial volume fraction (ve, ratio of Ktrans to reverse transfer constant, kep). In addition, MRCA extracellular distribution volume (VD) was estimated in the tumor and its borders, along with tumor blood flow (TBF) and peritumoral MRCA flux. Descriptors of parametric distributions were compared between the two times. Tumor extent was examined by hematoxylin and eosin (H&E) staining. Picrosirus red staining of secreted collagen was performed as an additional index for 9L cells. RESULTS: Test-retest differences between population summaries for any parameter were not significant (paired t and Wilcoxon signed rank tests). Bland-Altman plots showed no apparent trends between the differences and averages of the test-retest measures for all indices. The intraclass correlation coefficients showed moderate to almost perfect reproducibility for all of the parameters, except vp. H&E staining showed tumor infiltration in parenchyma, perivascular space and white matter tracts. Collagen staining was observed along the outer edges of main tumor mass. CONCLUSION: The data suggest the relative stability of these MR indices of tumor microenvironment over a 24h duration in this gliosarcoma model.

Detailed magnetic resonance imaging features of a case series of primary gliosarcoma.

Objective We aimed to characterise the magnetic resonance imaging (MRI) features of a case series of primary gliosarcoma, with the inclusion of diffusion-weighted imaging and perfusion imaging with dynamic susceptibility contrast MRI. Materials and methods We conducted a retrospective study of cases of primary gliosarcoma from the Pathology Department database from January 2006 to December 2014. Clinical and demographic data were obtained. Two neuroradiologists, blinded to diagnosis, assessed tumour location, signal intensity in T1 and T2-weighted images, pattern of enhancement, diffusion-weighted imaging and dynamic susceptibility contrast MRI studies on preoperative MRI. Results Seventeen patients with primary gliosarcomas had preoperative MRI study: seven men and 10 women, with a mean age of 59 years (range 27-74). All lesions were well demarcated, supratentorial and solitary (frontal n = 5, temporal n = 4, parietal n = 3); 13 tumours abutted the dural surface (8/13 with dural enhancement); T1 and T2-weighted imaging patterns were heterogeneous and the majority of lesions (12/17) showed a rim-like enhancement pattern with focal nodularities/irregular thickness. Restricted diffusion (mean apparent diffusion coefficient values 0.64 × 10-3 mm2/s) in the more solid/thick components was present in eight out of 11 patients with diffusion-weighted imaging study. Dynamic susceptibility contrast MRI study ( n = 8) consistently showed hyperperfusion in non-necrotic/cystic components on relative cerebral volume maps. Conclusions The main distinguishing features of primary gliosarcoma are supratentorial and peripheral location, well-defined boundaries and a rim-like pattern of enhancement with an irregular thick wall. Diffusion-weighted imaging and relative cerebral volume map analysis paralleled primary gliosarcoma with high-grade gliomas, thus proving helpful in differential diagnosis.

[A Patient with Primary Intraventricular Gliosarcoma and Long-term Survival - a Case Report]. / Pacientka s primárním intraventrikulárním gliosarkomem s dlouhodobým prezíváním - kazuistika.

BACKGROUND: Gliosarcoma is a rare, malignant CNS tumor with a very poor prognosis. Gliosarcoma is a variant of glioblastoma multiforme, which is characterized by the presence of both glial and mesenchymal components. The treatment strategy for gliosarcomas has not yet been determined clearly. CASE PRESENTATION: This case report presents a 23-year-old female patient who complained of increasing headaches, nausea and vomiting, and slight motor weakness in her left arm. An MRI scan of the brain showed a tumor filling the anterior part of the right lateral ventricle and extending into the right frontal lobe. Tumor extirpation was performed. Histology revealed gliosarcoma. Subsequently, the patient received concomitant chemoradiotherapy with temozolomide in the Stupp regimen. Following the fourth cycle of maintenance temozolomide chemotherapy, at eight months after diagnosis, an MRI scan detected progression of the tumor residue. The patient underwent another surgery and then received 10 cycles of second-line chemotherapy in the ICE (ifosfamide, carboplatin, and etoposide) regimen. She completed oncological therapy with minimal toxicity and follow-up MRI scans showed virtually no residual tumor. Another follow-up MRI scan, performed 28 months after diagnosis, demonstrated progression of the tumor residue again. A third tumor resection was performed 29 months after initial diagnosis. Histology again confirmed gliosarcoma. An early postoperative MRI scan showed subtotal resection with a tumor residue in eloquent areas and also suspected implantation metastasis in the spinal canal at the C2 level. From the neurological perspective, the patient was fully self-sufficient, and had only a very mild motor deficit in her left arm. Currently, at 31 months after initial diagnosis, the patient is in a stable condition and fully self-sufficient. CONCLUSION: Our case report shows that long-term survival can be achieved in a gliosarcoma patient exhibiting all the unfavorable features in clinical-pathological terms. The minimal recommended treatment is maximal resection followed by adjuvant radiotherapy. Our patient also underwent chemoradiotherapy with temozolomide in the Stupp regimen. Recurrence at eight months after diagnosis was managed by a repeat operation and high-dose combination chemotherapy, which kept the disease in remission for 20 months after the initial relapse. The lack of unequivocal rules for chemotherapy provides an opportunity to test less common treatment regimens.Key words: gliosarcoma - surgery - chemotherapy - radiotherapy - survivalThis study was supported in part by the grant No. NT13581-4/2012(86-91) of the Internal Grant Agency of the Czech Ministry of Health.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 26. 3. 2016Accepted: 27. 4. 2016.