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Purpose: The prognostic utility of MIB-1 labeling index (LI) in pediatric low-grade glioma (PLGG) has not yet conclusively been described. We assess the correlation of MIB-1 LI and tumor growth velocity (TGV), aiming to contribute to the understanding of clinical implications and the predictive value of MIB-1 LI as an indicator of proliferative activity and progression-free survival (PFS) in PLGG., Methods: MIB-1 LI of a cohort of 172 nonependymal PLGGs were comprehensively characterized. Correlation to TGV, assessed by sequential MRI-based three-dimensional volumetry, and PFS was analyzed., Results: Mean MIB-1 LI accounted for 2.7% (range: < 1-10) and showed a significant decrease to 1.5% at secondary surgery (p = .0013). A significant difference of MIB-1 LI in different histopathological types and a correlation to tumor volume at diagnosis could be shown. Linear regression analysis showed a correlation between MIB-1 LI and preoperative TGV (R 2  = .55, p < .0001), while correlation to TGV remarkably decreased after incomplete resection (R 2  = .08, p = .013). Log-rank test showed no association of MIB-1 LI and 5-year PFS after incomplete (MIB-1 LI > 1 vs ≤ 1%: 48 vs 46%, p = .73) and gross-total resection (MIB-1 LI > 1 vs ≤ 1%: 89 vs 95%, p = .75)., Conclusion: These data confirm a correlation of MIB-1 LI and radiologically detectable TGV in PLGG for the first time. Compared with preoperative TGV, a crucially decreasing correlation of MIB-1 LI and TGV after surgery may result in limited prognostic capability of MIB-1 LI in PLGG., (© 2024. The Author(s).)

Background and Purpose: To evaluate the feasibility of a multimodal approach involving dynamic contrast-enhanced (DCE) perfusion imaging and diffusion kurtosis imaging (DKI) in the preoperative imaging of brain tumors in a multicenter setting, and to evaluate the effect on diagnostic confidence and accuracy for tumor grade and type prediction., Materials and Methods: One hundred and thirty-three patients with brain tumors were imaged in six hospitals with a standardized multimodal protocol. Standard imaging and six parameter maps derived from DCE and DKI sequences were reviewed off-site by two independent readers. Image quality and diagnostic confidence were evaluated in qualitative analyses. Quantitative analyses were performed to assess diagnostic accuracy and the performance of DKI and DCE parameters for tumor grade differentiation and molecular tumor type determination., Results: Standardized acquisition of DCE and DKI maps was feasible with excellent image quality. Diagnostic confidence was significantly improved from 85 % to 96 % (p = 0.0005) by additional review of the DCE and DKI maps. The combination of mean kurtosis and CBV was particularly advantageous for differentiating low-grade and high-grade glioma, oligodendroglial vs. astrocytic, and IDH1/2 wild type vs. mutated tumors., Conclusion: A multimodal imaging approach with DCE and DKI improves diagnostic confidence and yields higher diagnostic accuracy for predicting tumor grade and type in adult-type glioma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In addition to surgical management, corticosteroids have proven to be beneficial in the management of acute symptoms related to CNS tumors, and have been widely used for many decades, with dexamethasone (DM) representing the most commonly used agent. However, lately published in vitro data possibly indicates a DM-induced suppression of oncogene-induced senescence (OIS) in a preclinical pediatric low-grade glioma (pLGG) model, which, alongside data associating perioperative DM treatment with reduced event-free survival in adult glioma, raises questions concerning the safety of DM treatment in pLGG. A total of 172 patients with pLGG were retrospectively analyzed concerning the impact of perioperative DM application on postoperative short- and long-term tumor growth velocity and progression-free survival (PFS). Three-dimensional volumetric analyses of sequential MRI follow-up examinations were used for assessment of tumor growth behavior. Mean follow-up period accounted for 60.1 months. Sixty-five patients (45%) were perioperatively treated with DM in commonly used doses. Five-year PFS accounted for 93% following gross-total resection (GTR) and 57% post incomplete resection (IR). Comparison of short- and long-term postoperative tumor growth rates in patients with vs without perioperative DM application showed no significant difference (short-term: 0.022 vs 0.023 cm 3 /month, respectively; long-term: 0.019 vs 0.023 cm 3 /month, respectively). Comparison of PFS post IR (5-year-PFS: 65% vs 55%, respectively; 10-year-PFS: 52% vs 53%, respectively) and GTR (5- and 10-years-PFS: 91% vs 92%, respectively) likewise showed similarity. This data emphasizes the safety of perioperative DM application in pLGG, adding further evidence for decision making and requested future guidelines., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: Despite excellent long-term overall survival rates, pediatric low-grade gliomas (pLGG) show high variety of clinical behavior regarding progress or senescence post incomplete resection (IR). This study retrospectively analyzes tumor growth velocity (TGV) of pLGG before surgery and after IR to investigate the impact of surgical extent, tumor location and molecular BRAF status on postoperative residual tumor growth behavior., Methods: Of a total of 172 patients with pLGG receiving surgical treatment, 107 underwent IR (66%). Fifty-three vs 94 patients could be included in the pre- and post-operative cohort, respectively, and were observed over a mean follow-up time of 40.2 vs 60.1 months. Sequential three-dimensional MRI-based tumor volumetry of a total of 407 MRI scans was performed to calculate pre- and postoperative TGV., Results: Mean preoperative TGV of 0.264 cm 3 /month showed significant deceleration of tumor growth to 0.085 cm 3 /month, 0.024 cm 3 /month and -0.016 cm 3 /month after 1st, 2nd, and 3rd IR, respectively (p < 0.001). Results remained significant after excluding patients undergoing (neo)adjuvant treatment. Resection extent showed correlation with postoperative reduction of TGV (R = 0.97, p < 0.001). ROC analysis identified a residual cut-off tumor volume > 2.03 cm 3 associated with a higher risk of progress post IR (sensitivity 78,6%, specificity 76.3%, AUC 0.88). Postoperative TGV of BRAF V600E-mutant LGG was significantly higher than of BRAF wild-type LGG (0.123 cm 3 /month vs. 0.016 cm 3 /month, p = 0.047)., Conclusion: This data suggests that extensive surgical resection may impact pediatric LGG growth kinetics post incomplete resection by inducing a significant deceleration of tumor growth. BRAF-V600E mutation may be a risk factor for higher postoperative TGV., (© 2022. The Author(s).)

Background: MR spectroscopy (MRS) measurements are common practice in the preoperative diagnostic regimen, but no evidence exists concerning their value in intraoperative MRI (iMRI) setting. We sought to examine the feasibility of intraoperative MRS and to assess the clinical value of the method in optimizing the gliomas resection., Methods: Forty-five patients with low- and high-grade gliomas underwent iMRI-assisted surgery, including pre- and intraoperative MRS measurements. During the intraoperative control scan, MRS was performed at the resection margin. Peak areas under the major metabolites (N-acetyl-aspartate: NAA; choline: Cho; and creatine: Cr) resonances were estimated, and their ratios entered in the statistical analysis., Results: Concerning preoperative MRS imaging, mean Cho/NAA and Cho/Cr ratios in low-grade gliomas were 2.3 and 1.2, respectively. The average Cho/NAA and Cho/Cr ratios in the high-grade gliomas were 3.9 and 2.3, respectively. In 12 out of 20 cases with low-grade gliomas, intraoperative conventional MR imaging showed suspected tumor remnant and MRS diagnosed correctly the tissue signal alterations in 10 out of those 12 cases. MRS could characterize gadolinium-enhancing or non-enhancing tumor remnants in all cases with high-grade tumors. Thus, it could help achieve total tumor resection unless the latter was contraindicated due to increased risk of neurological complications., Conclusions: MR spectroscopy (MRS) in an iMRI setting is feasible, facilitating preoperative glioma staging as well as satisfactory characterization of suspected tumor remnants. Thus, it may be helpful tool for an extended tumor resection.

Objective: To quantify and compare T2 signal and apparent diffusion coefficient (ADC) in pilocytic and pilomyxoid astrocytoma (PA and PMA) and correlate results with myxoid content., Methods: Echo-planar diffusion weighted images (DWI) and standard magnetic resonance imaging (MRI) findings were reviewed retrospectively in patients with PA (n=34) and PMA (n=8). Regions of interest (ROIs) were drawn on ADC maps within tumor parts with lowest ADC values. Apparent diffusion coefficient values in tumor were normalized to those in cerebrospinal fluid (ADC/CSF). The ratio of T2 signal intensity in solid tumor parts to CSF (T2/CSF) was registered. Myxoid matrix was histologically quantified retrospectively in 8 PMAs and 17 PAs and correlated with imaging findings., Results: Mean ADC/CSF for PA and PMA was 0.53±0.10 and 0.69±0.10 (p<0.01). Mean T2/CSF for PA and PMA was 0.78±0.19 and 0.93±0.09 (p<0.01). Mean proportion of myxoid tumor matrix in PA was 50% (range, 10-100%) and 93% (range, 90-100%) in PMA (p=0.004). Eight patients (32%; all PA) had less than 50% myxoid content and 17 (68%; 8 PA; 9 PMA) had more. There was positive correlation of ADC/CSF, T2/CSF and ADC (r2=0.61, 0.65 and 0.60 respectively) and significant difference between the groups with more and less than 50% myxoid content (p=0.01 for ADC/CSF and T2/CSF and p=0.02 for ADC)., Conclusions: General imaging features of PA and PMA are non-specific, ADC values and T2 signal intensity are generally higher in the latter, reflecting the proportion of myxoid matrix in these tumors.

A recent report of the feasibility of simultaneous PET/MR imaging of the healthy human brain has sparked excitement in the field of neuroimaging because of its potential influence and utility in clinical neuroscience research. The aim of this communication is to discuss the benefits and current drawbacks of the hybrid imaging system and to highlight some perspectives of the new technique for brain neoplasms.

Objective: The purpose of this study was to determine whether lymphoma and astrocytic tumor infiltrating the corpus callosum can be reliably differentiated with measurement of water diffusivity., Materials and Methods: Echo-planar diffusion-weighted MR images of 27 patients with glioblastoma multiforme, five patients with low-grade astrocytoma, five patients with gliomatosis cerebri, and nine patients with primary lymphoma infiltrating the corpus callosum were reviewed retrospectively. Regions of interest were drawn on apparent diffusion coefficient (ADC) maps inside the callosal tumor. ADCs were normalized by calculation of the ratio between the ADC of the tumor and the ADC of an uninvolved region of corpus callosum., Results: The mean ADC of glioblastoma multiforme was 1.13 +/- 0.31 (SD) x 10(-3) mm(2)/s, and the mean tumor to corpus callosum ADC ratio was 1.51 +/- 0.46; of low-grade astrocytoma, 1.14 +/- 0.23 x 10(-3) mm(2)/s and 1.54 +/- 0.28; gliomatosis cerebri, 1.01 +/- 0.20 x 10(-3) mm(2)/s and 1.31 +/- 0.36; and lymphoma, 0.71 +/- 0.13 x 10(-3) mm(2)/s and 0.93 +/- 0.19. The difference between the mean tumor to corpus callosum ADC ratio of lymphoma and that of all grades of astrocytoma (1.48 +/- 0.43) was statistically significant (p < 0.001). The optimal ADC threshold for discriminating astrocytic tumor and lymphoma was 0.90 x 10(-3) mm(2)/s (sensitivity, 84%; specificity, 89%). The optimal threshold for tumor to corpus callosum ADC ratio was 1.22 (sensitivity, 73%; specificity, 100%)., Conclusion: The water diffusivity and the ADC ratio of the tumor to normal-appearing corpus callosum of astrocytic tumor differ significantly from those of lymphoma infiltrating the corpus callosum, allowing reliable differentiation of the two types of tumor.

Gangliogliomas usually present as benign tumors corresponding to World Health Organization (WHO) Grade I. Very rarely, gangliogliomas show histological features of malignancy and are then classified as anaplastic gangliogliomas of WHO Grade III or IV. In most cases, anaplastic gangliogliomas developed after radiation therapy or progression from a pre-existing low-grade ganglioglioma. Here, we report the case of a 77-year-old male patient who was operated on a primary ganglioglioma with a highly anaplastic glial component corresponding to a small-cell glioblastoma. To our knowledge, this is the first reported case of a primary anaplastic ganglioglioma with a small-cell glioblastoma component.

Gangliogliomas are rare CNS neoplasms mostly occuring in young adults and are usually assigned to WHO grade I. The few cases of WHO grade IV gangliogliomas were either primarily malignant glio-neuronal tumors or underwent malignant progression from other WHO grades after radiotherapy. Herein, we present the case of a now 47-year-old female patient presenting with a benign ganglioglioma and showing a tumor recurrence 2 years later with an anaplastic ganglioglioma, assigned to WHO grade IV, with malignant transformation in both glial and neuronal components. The presented case is the first reported low-grade ganglioglioma rapidly progressing to a WHO grade IV glio-neuronal tumor not being associated with radiotherapy and showing malignant transformation in both astroglial and neuronal tumor cell components.

The authors performed a comprehensive analysis of the functional outcome of 10 patients who had survived 5 years from a diagnosis of glioblastoma. Neurologic deficits were mild in most patients, but neuropsychological testing demonstrated cognitive deficits in all patients. Depression and anxiety were common. Although most patients thought that their social functioning and work ability were impaired, little reduction in overall quality of life was perceived.

Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Continuous oral low-dose chemotherapy with methotrexate (MTX) and cyclophosphamide (CPM) has modest activity in heavily pretreated patients with breast cancer. We explored the efficacy of 100 mg CPM daily and 5 mg MTX twice weekly in relapsed glioblastoma. Ten patients, 22-59 years old, with a Karnofsky score of 50% or higher who had failed at least two chemotherapies were accrued. No toxicity was observed. No patient showed a complete or partial response. Five of 10 patients progressed within 2 months of therapy. Another five patients progressed after 3-4.5 months. The median time to progression was 2.5 months. The median overall survival after start of MTX/CPM was 6.9 months (range 0.5-18.8 months). Since the progression-free survival rate at 6 months was 0%, the trial was prematurely closed.

Short echo time (TE) proton MR spectra of the brain include signals of several metabolites as well as macromolecules. In various pathologies, such as brain tumors and multiple sclerosis (MS), the presence of mobile lipids or pathologically altered macromolecules may provide useful additional diagnostic information. A reliable quantitation of these resonances, however, is often not possible due to the lack of adequate prior knowledge. Furthermore, even if advanced fitting procedures are used, a reliable evaluation of metabolites in the presence of pathological lipids or macromolecules often fails if the latter are omitted in the spectral evaluation. In this study, a method is presented for the simultaneous evaluation of all visible components, including metabolites, lipids, and macromolecules, by the use of the fitting procedure LCModel. A standard basis set of brain metabolites was extended by inclusion of parameterized components for macromolecules and lipids that were derived from metabolite-nulled in vivo spectra of normal brain and high-grade gliomas, respectively. The improved spectral quantitation is demonstrated in glial brain tumors and MS lesions as well as in normal brain. It is pointed out that both macromolecules and lipids must be included to provide a proper spectral evaluation., (Copyright 2003 Wiley-Liss, Inc.)

Magnetic resonance perfusion and diffusion studies were undertaken to clarify the significance of ischemia in the pathogenesis of peritumoral brain edema in patients with meningiomas. Included in this study were 26 patients with 27 meningiomas and 5 gliomas. Perfusion-weighted imaging (PWI) was performed using a gradient-echo, echo-planar-imaging (EPI) sequence for calculation of the relative regional cerebral blood volume (rrCBV) and the relative regional cerebral blood flow index (rrCBFi). Furthermore, multi-slice spin-echo EPI sequences were applied in order to obtain anisotropic and isotropic diffusion-weighted imaging (DWI). Apparent diffusion coefficient (ADC) values were then calculated for peritumoral brain parenchyma from tumors, with and without edema, using various diffusion sensitivities. Meningiomas without edema demonstrated a minimal increase of perfusion parameters in the peritumoral brain tissue. In contrast, cases with brain edema had highly significant ( p<0.0005) lower rrCBV and rrCBFi. The edema index (EI) correlated strongly with the rrCBV. A fitting procedure resulted into the following mathematical relation: EI=0.1/rrCBV(2). The DWI showed a significantly larger ADC value within areas of brain edema, compared with the normal white matter (0.74 x 10(-3) vs 1.55 x 10(-3) mm(2)/s; p<0.0001). Increases in EI correlated with increases in ADC values. In 31% of the meningiomas associated with edema, areas with increased signal, probable ischemia, demonstrated significantly lower ADC values, in comparison with the rest of the edematous areas. These areas were confined to tissue immediately adjacent to the tumor. In general, the decrease in rrCBV in brain edema represents a consequence from, rather than a cause of, vasogenic edema. Ischemic alterations can be regarded as secondary, facultative phenomena in the pathogenesis of meningioma-related brain edema.

Object: In a prospective study, 28 patients with 32 intracranial meningiomas were examined to determine the role of hydrodynamic interaction between tumor and surrounding brain tissue in the pathogenesis of peritumoral brain edema., Methods: Gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA), an extracellular contrast agent used for routine clinical imaging, remains strictly extracellular without crossing an intact blood-brain barrier. Therefore, it is well suited for investigations of hydrodynamic extracellular mechanisms in the development of brain edema. Spin-echo T1-weighted magnetic resonance images were acquired before and after intravenous administration of 0.2 mmol/kg Gd-DPTA. Additional T1-weighted imaging was performed 0.6, 3.5, and 6.5 hours later. No significant Gd-DPTA diffused from tumor into peritumoral brain tissue in 12 meningiomas without surrounding brain edema. In contrast, in 17 of 20 meningiomas with surrounding edema, contrast agent in peritumoral brain tissue was detectable after 3.5 hours and 6.5 hours. In three of 20 meningiomas with minimum surrounding edema (<5 cm3), contrast agent effusion was absent. After 3.5 hours and 6.5 hours strong correlations of edema volume and the maximum distance of contrast spread from the tumor margin into adjacent brain parenchyma (r = 0.84 and r = 0.87, respectively, p < 0.0001) indicated faster effusion in larger areas of edema., Conclusions: The results of this study show that significant contrast agent effusion from the extracellular space of the tumor into the interstitium of the peritumoral brain tissue is only found in meningiomas with surrounding edema. This supports the hypothesis that hydrodynamic processes play an essential role in the pathogenesis of peritumoral brain edema in meningiomas.

The purpose of the present study was to analyse specific advantages of calculated parameter images and their limitations using an optimized echo-planar imaging (EPI) technique with high spatial and temporal resolution. Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) was performed in 12 patients with cerebrovascular disease and in 13 patients with brain tumours. For MR imaging of cerebral perfusion an EPI sequence was developed which provides a temporal resolution of 0.68 s for three slices with a 128 x 128 image matrix. To evaluate DSC-MRI, the following parameter images were calculated pixelwise: (1) Maximum signal reduction (MSR); (2) maximum signal difference (delta SR); (3) time-to-peak (Tp); and (4) integral of signal-intensity-time curve until Tp (SInt). The MSR maps were superior in the detection of acute infarctions and delta SR maps in the delineation of vasogenic brain oedema. The time-to-peak (Tp) maps seemed to be highly sensitive in the detection of poststenotic malperfused brain areas (sensitivity 90%). Hyperperfused areas of brain tumours were detectable down to a diameter of 1 cm with high sensitivity (> 90%). Distinct clinical and neuroradiological conditions revealed different suitabilities for the parameter images. The time-to-peak (Tp) maps may be an important advantage in the detection of post-stenotic "areas at risk", due to an improved temporal resolution using an EPI technique. With regard to spatial resolution, a matrix size of 128 x 128 is sufficient for all clinical conditions. According to our results, a further increase in matrix size would not improve the spatial resolution in DSC-MRI, since the degree of the vascularization of lesions and the susceptibility effect itself seem to be the limiting factors.

We report a man with a ruptured intracranial dermoid cyst, suffering from headache, nausea, vomiting and a generalised seizure. MRI was performed before and 2 weeks after surgical resection. On T1-weighted images the tumour gave high signal, as did fatty material in the frontal and parietal brain sulci. Identification of this hyper-intense material as lipids was possible by chemical-shift-selective 3D gradient-echo imaging, which provided excellent contrast between the subarachnoid lipids and the adjacent normal brain, with a good spatial resolution. Possible complications of subarachnoid and intraventricular lipid particles after dermoid cyst rupture are discussed and the diagnostic value of 3 D chemical-shift-selective additional to conventional T-1-weighted spin-echo images in identification of even small amounts of fat is emphasised.

Purpose: To investigate whether exact evaluation of the dynamic contrast enhancement pattern within intracranial tumors can help to classify tumor histology and vascularity., Method: Forty-nine patients suffering from different intra- and extraaxial intracranial tumors underwent MR-examination in a 1.5-T superconductive whole body system. After rapid injection of Gd-DTPA, 48 images were acquired during the first 1.5 to 2 minutes of contrast enhancement within the tumors. A fast snapshot-FLASH imaging technique allowed measurement times of 1 second per image. Appearance of Gd-DTPA in a venous sinus served as a temporal reference point. Transformation of 48 discrete measurement points (mean signal values of the enhancing tumor region) into a continuous curve, using a cubic spline approximation, allowed calculation of the time of maximum signal increase (Tm1) and the following time of half maximum increase (Tm2). These time parameters were compared to histopathologic findings, especially the degree of tumor vascularization., Results: Significantly different dynamic patterns of the early enhancement period were found for the different tumors. All eight neurinomas, typically less vascularized than most meningiomas, showed a characteristically prolonged contrast enhancement with a long Tm2. Histopathologic findings concerning the degree of vascularization showed two subtypes in meningiomas (n = 17) as well as in pituitary macroadenomas (n = 7). This was confirmed by dynamic evaluation in all cases, in the sense that short Tm1 and Tm2 were found in cases with higher degrees of vascularization. Negatives values of Tm1 were measured in two glomus jugulare tumors, reflecting the arterialization of these vascular tumors. In neuroepithelial tumors (n = 15), the glioblastomas (n = 7) showed very short Tm1 compared to the lower grade gliomas (n = 8). This is explained by histologic findings of pathologic vessels with arteriovenous shunts., Conclusion: The evaluated dynamic time parameters can be used to narrow differential diagnostic possibilities and to infer the degree of vascularization of intracranial tumors.