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  • 1
    Language: English
    In: Radiology, March 2010, Vol.254(3), pp.876-81
    Description: To characterize the non-Gaussian diffusion patterns of cerebral glioma microstructure with respect to the different glioma grades by using a new method called diffusional kurtosis (DK) imaging. In this study with institutional review board approval and patient consent, diffusional measures of mean kurtosis (MK), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were compared prospectively. Data were normalized to the contralateral white matter. A Mann-Whitney test was used to compare each histologic glioma subtype regarding the diffusion measurements. Receiver operating characteristic curves were used to test for the parameter with the best sensitivity and specificity for glioma grade discrimination. In 34 patients with cerebral gliomas (five World Health Organization [WHO] grade II astrocytomas, 13 WHO grade III astrocytomas, and 16 WHO grade IV glioblastomas multiforme), significantly different diffusion patterns were found among the three glioma groups. MK values increased with higher glioma malignancy, whereas ADCs tended to decrease with higher malignancy; FA values did not differ significantly among tumor groups. Significant differences between astrocytoma grades WHO II and WHO III were demonstrated only by DK values. Area under the receiver operating characteristic curve was highest for normalized MK (0.972) during testing to discriminate between low- and high-grade gliomas. This study demonstrates specific diffusion patterns for low- and high-grade gliomas, showing that DK imaging is able to depict microstructural changes within glioma tissue and is able to help differentiate among glioma grades. (c) RSNA, 2010.
    Keywords: Brain Neoplasms -- Diagnosis ; Diffusion Magnetic Resonance Imaging -- Methods ; Glioma -- Diagnosis
    ISSN: 00338419
    E-ISSN: 1527-1315
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  • 2
    Language: English
    In: Strahlentherapie und Onkologie, 2011, Vol.187(11), pp.722-728
    Description: Byline: Johanna Gerstein (1), Kea Franz (2), Joachim P. Steinbach (3), Volkert Seifert (2), Claus Rodel (1), Christian Weiss (1,4) Keywords: Glioblastoma multiforme; radiochemotherapy; temozolomide; Glioblastoma multiforme; Radiochemotherapie; Temozolomid Abstract: Background The objective of this retrospective analysis was to assess long-term outcome and prognostic factors of unselected patients treated for glioblastoma (GB) at a single center with surgery, standard radiotherapy (RT), and concomitant temozolomide (TMZ). From 1999--2005, the institutional protocol included surgery and RT with TMZ. From 2005 on, adjuvant TMZ was routinely added. Patients and Methods Between April 1999 and September 2009, 181 patients with GB were treated with RT (60 Gy in 30 fractions) and concomitant TMZ (75 mg/m.sup.2/day throughout RT). Biopsy only had been performed in 53 patients (29.3%), 128 patients (70.7%) had undergone resection, which was complete based on postoperative MRI in 51 patients (28.2%). Adjuvant TMZ was applied in 67 of 181 patients (37%). Results Median overall survival (OS) and progression-free survival (PFS) were 15.0 (95% CI, 13.1--16.8) and 7.2 months (95% CI, 5.9--8.5), respectively. After complete resection, partial/subtotal resection and biopsy, median OS was 23.20, 14.75, and 7.89 months (p 〈 0.001), respectively. In multivariate Cox proportional hazards regression models, extent of resection (p 〈 0.0001), Karnofsky's performance score (p 〈 0.0001) and adjuvant TMZ (p = 0.001) were significant independent prognostic factors for OS. RT with concomitant TMZ was well tolerated in the majority of patients and could be completed as scheduled in 146 patients (80.7%), while 11 patients (6.1%) discontinued RT. Another 35 patients (19.3%) interrupted concomitant chemotherapy. Conclusion RT with concomitant TMZ is a feasible regimen with acceptable toxicity in routine practice. Our data are compatible with a beneficial effect of adjuvant TMZ on OS and PFS. Abstract (German): Hintergrund Ziel dieser retrospektiven Analyse einer monoinstitutionellen Serie war es, Langzeitergebnisse sowie Prognosefaktoren nach Operation und simultaner Radiochemotherapie (RCT) mit Temozolomid (TMZ) zu untersuchen. Zwischen 1999 und 2005 erfolgte nach Operation eine RCT mit TMZ seit 2005 wurde routinemassig eine adjuvante TMZ-Chemotherapie hinzugefugt. Patienten und Methoden Von 04/1999 bis 9/2009, wurden 181 GB-Patienten mit einer kombinierten RCT (60 Gy in 30 Fraktionen) mit TMZ 75 mg/m.sup.2/Tag wahrend der RT behandelt. Eine alleinige Biopsie lag bei 53 Patienten (29,3 %) vor. 128 Patienten (70,7 %) wurden reseziert davon erreichten 51 Patienten (28,2 %) nach Massgaben eines postoperativen MRT eine komplette Resektion. Eine adjuvante TMZ-Therapie erhielten 67 der 181 Patienten (37 %). Ergebnisse Das mediane Gesamtuberleben (GU) und das progressionsfreie Uberleben (PFU) lag bei 15,0 (95 %-CI: 13,1--16,8 Monate) bzw. 7,2 Monaten (95 %-CI: 5,9--8,5 Monate). Nach kompletter Resektion, partieller/subtotaler Resektion bzw. Biopsie betrug das mediane GU 23,2 bzw. 14,75 und 7,89 Monate (p 〈 0,001). In der multivariaten Analyse waren Resektionsstatus (p 〈 0,0001), Karnofsky-Index (p 〈 0,0001) und adjuvante TMZ-Therapie (p = 0,001) unabhangige prognostische Faktoren. Von der Mehrzahl der Patienten wurde die kombinierte RCT gut vertragen und konnte bei 146 Patienten (80,7 %) vollstandig durchgefuhrt werden. Bei 11 Patienten (6,1 %) wurde die RT abgebrochen. Bei weiteren 35 Patienten wurde die konkomitante Chemotherapie unterbrochen. Schlussfolgerung Die kombinierte RCT mit TMZ ist in der klinischen Routine ein gut vertragliches Therapieregime mit einer akzeptablen Toxizitat. Die adjuvante Chemotherapie mit TMZ war mit einer Verbesserung des GU und PFU assoziiert. Author Affiliation: (1) Department of Radiotherapy and Oncology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany (2) Department of Neurosurgery, Johann Wolfgang Goethe University, Frankfurt/Main, Germany (3) Dr. Senckenberg Institute of Neurooncology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany (4) Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany Article History: Registration Date: 01/01/2011 Received Date: 25/10/2010 Accepted Date: 16/06/2011 Online Date: 28/10/2011
    Keywords: Glioblastoma multiforme ; radiochemotherapy ; temozolomide
    ISSN: 0179-7158
    E-ISSN: 1439-099X
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  • 3
    Language: English
    In: Journal of Neuro-Oncology, 2012, Vol.107(3), pp.599-607
    Description: The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surgery than for first surgery, and sought to identify factors associated with the occurrence of postoperative infarction. Therefore, we searched our database to identify patients who were operated for primary or recurrent glial tumors between October 2007 and October 2010. We analyzed 177 procedures, of which 130 (73.4%) were first surgeries and 47 (26.5%) were repeat. Initial WHO grades, KPS scores, and age were evenly distributed between the groups. Forty-six (26.0%) patients had new DWI lesions on their postoperative MRI scan. Eighteen (10.2%) patients had new lesions greater than 4 cm 3 . Among these were 11 (6.2%) patients, for whom the new lesion caused neurologic deficit. There was no difference between first and repeat surgery with regard to the occurrence of new DWI lesions (27.7 vs. 21.3%, P  = 0.77) or neurological deficits (10.0 vs. 10.6%, P  = 1.0). Tumor location in the insula, operculum, and temporal lobe was found to be significantly associated with the occurrence of new DWI lesions. We conclude that repeat surgery should not be withheld as a treatment option for patients with recurrent gliomas for fear of a higher risk of postoperative infarction or new neurologic deficit than the first surgery.
    Keywords: Glioma ; Infarction ; Repeat surgery ; DWI lesion ; Retrospective analysis
    ISSN: 0167-594X
    E-ISSN: 1573-7373
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  • 4
    Language: English
    In: Journal of Neuro-Oncology, 2011, Vol.103(3), pp.575-584
    Description: We observed a stripe-like pattern of regional cerebral blood volume (rCBV) increase in a defined region adjacent to the contrast enhancement (CE) on MRI of glioblastomas (GBM) that we defined as the “striate sign” (SS). We hypothesized that the SS marks infiltration of GBM outside the CE volume transforming into future CE tumor in the follow-up. T2*-weighted dynamic susceptibility-weighted CE (DSC)-MRI, and T1 and T2-weighted images (WI) of 16 patients with GBM were retrospectively evaluated in a baseline MRI performed before neurosurgery. In seven of these patients we also performed a 1 H MR spectroscopic imaging ( 1 H MRSI). The regions of interest (ROI) delineating the SS were defined on rCBV maps for each patient. ROIs were overlaid on follow-up T1-WI and T2-WI MRI performed 3, 6, and 9 months after neurosurgery. Size and maximum signal intensity (max SI) of de novo CE within the area of the SS were analyzed. Statistical analysis was performed with the Friedman test ( P  〈 0.05). In 15/16 patients de novo CE completely covered the area of the SS within nine months. Normalized max SI of de-novo CE of the 3, 6, and 9-months follow-up MR examinations were significantly higher than in the baseline MRI ( P  〈 0.001). Normalized choline was increased within the SS in all patients with de novo CE ( n  = 6). De-novo CE appeared within the SS in all patients (96% of all slices). This implies that the SS might indicate the site of future CE tumor, which represents the area of tumor growth after neurosurgery.
    Keywords: Perfusion MRI ; rCBV ; De novo CE ; Glioblastoma ; Choline
    ISSN: 0167-594X
    E-ISSN: 1573-7373
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  • 5
    Language: English
    In: European Journal of Paediatric Neurology, 2011, Vol.15(3), pp.214-221
    Description: To investigate whether pathologically similar astrocytomas in adults and children may also show metabolic similarities in proton magnetic resonance spectroscopy ( H-MRS) and whether the MRS data could help to differentiate between low and high grade gliomas for the different groups. Twelve children (5 WHO II astrocytomas, 7 WHO III astrocytomas) and 37 adults (21 WHO II astrocytomas, 16 WHO III astrocytomas) were included in this study. MR spectroscopic data were evaluated retrospectively using normalized measures of total choline (tCho), N-acetyl-aspartate (NAA) and total creatine (tCr). These metabolites were used to differentiate between WHO II and WHO III astrocytomas in children and adults. Histopathological grading was performed using WHO criteria. H-MRS was carried out prior to the commencement of any treatment. Signal intensities of tCho, NAA and tCr were normalized to their values in contralateral brain tissue. The resulting concentration ratios were then used to calculate the change in the intratumoural ratio of NAA to tCho. A Mann–Whitney -Test was performed to evaluate differences within the respective groups. In both groups, loss of NAA and increase of tCho were more pronounced in WHO III than in WHO II astrocytoma. The best discriminator to differentiate between low and high grade gliomas was found to be the ratio of NAA/tCho (  〈 0.01). The normalized metabolite signal intensities ratio NAA to tCho is the most accurate in differentiating between low and high grade astrocytomas in both children and adults.
    Keywords: 1h-Mr Spectroscopy ; Astrocytomas ; Choline ; N-Acetyl-Aspartate ; Children ; Medicine
    ISSN: 1090-3798
    E-ISSN: 1532-2130
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  • 6
    Language: English
    In: Journal of Neuro-Oncology, 2010, Vol.99(1), pp.49-56
    Description: Bevacizumab is an anti-vascular endothelial growth factor (VEGF) antibody with activity against recurrent malignant glioma inducing high rates of objective responses as assessed by magnetic resonance imaging (MRI). However, the mechanisms of the anti-tumor action of bevacizumab are controversial. In particular, it is unclear whether and when bevacizumab induces hypoxia in gliomas. Vascular normalization with hyperperfusion and enhanced oxygen delivery to the tumor has been suggested as an alternative mechanism. We analyzed diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps in 18 consecutive patients with recurrent malignant glioma before and after exposure to bevacizumab. Stroke-like lesions with diffusion restriction on DWI and corresponding ADC decrease were induced by bevacizumab within the previously enhancing tumor area in 13 of 18 patients. These lesions were detectable as early as 4 weeks after initiation of therapy and were maintained for up to 80 weeks. In one patient, an ADC-decreased lesion was biopsied, and histology showed atypical necrosis and nuclear hypoxia-inducible factor 1alpha upregulation but no tumor recurrence. Normalized regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) were analyzed in selected patients. Both parameters were decreased in responders with diffusion-restricted lesions. Within the tumor bed, bevacizumab induces diffusion-restricted lesions in the presence of reduced rCBF and rCBV. The cause of these alterations is unclear but may involve atypical necrosis and chronic hypoxia.
    Keywords: ADC ; Glioma ; Bevacizumab ; Irinotecan ; Perfusion
    ISSN: 0167-594X
    E-ISSN: 1573-7373
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  • 7
    Language: English
    In: Acta neurochirurgica, November 2010, Vol.152(11), pp.1893-9
    Description: Increased relative cerebral blood volume (rCBV) was previously found in peritumoural oedema of glioblastomas (GBM). Supposing that peritumoural rCBV is not increased in metastases, we aimed to evaluate whether rCBV values of the whole peritumoural area are accurate to differentiate solitary metastasis from GBM irrespective of the peritumoural oedema. Contrast-enhanced T1-weighted (T1-w) and T2*-weighted dynamic susceptibility contrast MRI was performed in 52 patients with contrast-enhancing solitary brain tumours before surgery. In each T1-w slice depicting the contrast-enhancing tumour, a rim within approximately 15 mm was defined in the peritumoural area. The rCBV values were normalised to rCBV values of the contralateral normal white matter. Differences between metastases and GBM for normalised rCBV values for each slice were determined with the Mann-Whitney U test (p 〈 0.05). Histopathological examination revealed 29 GBM and 23 metastases. Peritumoural rCBV was significantly lower in metastases than in GBM (p 〈 0.01). Using the cutoff value 1.0 for discriminating metastases from GBM yielded a sensitivity of 96%, specificity of 64%, a positive predictive value of 68% and a negative predictive value of 95%. The rCBV in the peritumoural area of contrast-enhancing brain tumours has a high diagnostic accuracy to discriminate metastases from GBM irrespective of surrounding oedema and without the bias of slice selection and ROI positioning. Metastases should be excluded, if at least one tumour-depicting slice reveals an increase of peritumoural rCBV compared to the normal contralateral brain (normalised rCBV value 〉1). Conversely, the decrease of peritumoural rCBV may not reliably exclude GBM.
    Keywords: Brain Neoplasms -- Blood Supply ; Cerebrovascular Circulation -- Physiology ; Glioma -- Blood Supply ; Magnetic Resonance Imaging -- Methods ; Neoplasm Metastasis -- Diagnosis
    ISSN: 00016268
    E-ISSN: 0942-0940
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  • 8
    Language: English
    In: Brain Tumor Pathology, 2010, Vol.27(2), pp.65-70
    Description: Our purpose was to investigate whether in vivo proton magnetic resonance spectroscopic imaging, using normalized concentrations of total choline (tCho) and total creatine (tCr), can differentiate between WHO grade I pilocytic astrocytoma (PA) and diffuse, fibrillary WHO grade II astrocytoma (DA) in children. Data from 16 children with astrocytomas (11 children with PA and 5 children with DA) were evaluated retrospectively. MRS was performed before treatment in all patients with histologically proven low-grade astrocytomas. Metabolite concentrations of tCho and tCr were normalized to the respective concentration in contralateral brain tissue. The Mann-Whitney U test was performed to evaluate differences between these two groups. Normalized tCho did not show any statistically significant difference between the two groups. There was a strong trend ( P = 0.07) toward higher values of normalized tCr in the DA group. For 3 of 5 children with DA, lactate was detectable, but only 1 of 11 children with PA showed lactate. We concluded that choline as a single parameter is not reliable in the differential diagnosis of low-grade astrocytomas in children. Our results suggest that tCr concentrations combined with lactate will be helpful in the differential diagnosis of PA and DA in children.
    Keywords: Proton magnetic resonance spectroscopy ; Pilocytic astrocytoma ; Diffuse ; Fibrillary astrocytoma ; Children
    ISSN: 1433-7398
    E-ISSN: 1861-387X
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  • 9
    Language: English
    In: Journal of Neuro-Oncology, 2011, Vol.103(3), pp.663-672
    Description: First-pass contrast-enhanced dynamic perfusion imaging provides information about the regional cerebral blood volume (rCBV), an increase of which indicates neovascularization. MR spectroscopic imaging informs about metabolite changes in brain tumors, with elevated choline (Cho) values revealing cell proliferation and density, and the glial metabolite creatine (Cr) representing high-energy storage. This study investigates metabolite changes within the tumor voxel of maximal rCBV value (rCBV max ). Anatomically coregistered parameter maps of rCBV, Cho and Cr were evaluated in 36 patients with primary or recurrent WHO grade III or IV gliomas. Apart from Cho and Cr values within the voxel of rCBV max (Cho perf , Cr perf ), the maximal Cho and Cr values of the tumor tissue were recorded (Cho max , Cr max ). The correlation between these parameters was analyzed with Spearman’s rho test while a binomial test was performed to check whether Cho max  = Cho perf and Cr max  = Cr perf . We found that, in 29 of the 36 patients, neither Cho nor Cr had their maxima in the voxel of rCBV max (Cho perf, Cr perf  〈 Cho max , Cr max , P  〈 0.001). However, Cho perf was highly correlated with Cho max ( r  = 0.76, P  〈 0.001) and Cr perf with Cr max ( r  = 0.47, P  〈 0.001). Further Cho perf correlated with Cr perf ( r  = 0.55, P  〈 0.001). Neither of the spectroscopic parameters (Cho max, Cr max, Cho perf, Cr perf, ) correlated with rCBV max . In conclusion, in WHO grade III and IV gliomas the voxel with maximal rCBV often differs from the voxel with the maximal Cho and Cr, indicating the spatial divergence between neovascularization and tumor cell proliferation, cell density and glial processes. However, tCho and tCr changes within the area of neovascularization are positively correlated with the maximal increase within the tumor tissue. These results demonstrate aspects of regional tumor heterogeneity as characterized by different MR modalities that, apart from histopathological grading might be crucial for neurosurgical biopsy as well as for antiangiogenetic and future molecular therapies.
    Keywords: Heterogeneity ; Malignant gliomas ; MR spectroscopy ; Choline ; MR perfusion ; Cerebral blood volume
    ISSN: 0167-594X
    E-ISSN: 1573-7373
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  • 10
    Language: English
    In: Journal of Neuro-Oncology, 2011, Vol.103(3), pp.765-770
    Description: Gliosarcoma is a relatively rare and highly malignant brain tumor consisting of both a glioblastoma and a mesenchymal component. Because of the natural barrier of the dura mater, that prevents intra or extradural neoplasm dissemination, cases of penetration of the dura and cranium by gliosarcomas without previous surgery or radiation are very rarely reported. We report an unusual case of gliosarcoma that involved the temporal skull base and the dura without antecedent radiation or surgery, although the lesion traversed the dura without radiologic or gross interruption of the dura. Remarkable in our case is the initial integrity of cerebral parenchyma. Follow-up revealed a tumorous infiltration of the temporal lobe almost one year after initial diagnosis. Thus the origin of the gliosarcoma in our case seemed to be extradural in the temporal skull base. Furthermore, this report demonstrates that extensive multi-modality treatment might be effective in patients with gliosarcomas and poor prognostic factors, for example unmethylated MGMT status.
    Keywords: Gliosarcoma ; Extradural growth ; Bone infiltration ; Infratemporal fossa penetration
    ISSN: 0167-594X
    E-ISSN: 1573-7373
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