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Zetterling, Maria
Publications (10 of 21) Show all publications
Freyschlag, C. F., Krieg, S. M., Kerschbaumer, J., Pinggera, D., Forster, M.-T., Cordier, D., . . . Mandonnet, E. (2018). Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.. Journal of Neuro-Oncology, 139(3), 699-711
Open this publication in new window or tab >>Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.
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2018 (English)In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 139, no 3, p. 699-711Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers.

METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery.

RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI.

CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET.

IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Keywords
Imaging in LGG, Low-grade glioma, Minimal core of imaging, Response criteria
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-356147 (URN)10.1007/s11060-018-2916-3 (DOI)000443861200020 ()29992433 (PubMedID)
Available from: 2018-07-16 Created: 2018-07-16 Last updated: 2018-10-29Bibliographically approved
Roodakker, K. R., Alhuseinalkhudhur, A., Al-Jaff, M., Georganaki, M., Zetterling, M., Berntsson, S. G., . . . Smits, A. (2018). Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity.. European Journal of Nuclear Medicine and Molecular Imaging
Open this publication in new window or tab >>Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity.
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089Article in journal (Refereed) Epub ahead of print
Abstract [en]

PURPOSE: Oligodendrogliomas are heterogeneous tumors in terms of imaging appearance, and a deeper understanding of the histopathological tumor characteristics in correlation to imaging parameters is needed. We used PET-to-MRI-to-histology co-registration with the aim of studying intra-tumoral 11C-methionine (MET) uptake in relation to tumor perfusion and the protein expression of histological cell markers in corresponding areas.

METHODS: Consecutive histological sections of four tumors covering the entire en bloc-removed tumor were immunostained with antibodies against IDH1-mutated protein (tumor cells), Ki67 (proliferating cells), and CD34 (blood vessels). Software was developed for anatomical landmarks-based co-registration of subsequent histological images, which were overlaid on corresponding MET PET scans and MRI perfusion maps. Regions of interest (ROIs) on PET were selected throughout the entire tumor volume, covering hot spot areas, areas adjacent to hot spots, and tumor borders with infiltrating zone. Tumor-to-normal tissue (T/N) ratios of MET uptake and mean relative cerebral blood volume (rCBV) were measured in the ROIs and protein expression of histological cell markers was quantified in corresponding regions. Statistical correlations were calculated between MET uptake, rCBV, and quantified protein expression.

RESULTS: A total of 84 ROIs were selected in four oligodendrogliomas. A significant correlation (p < 0.05) between MET uptake and tumor cell density was demonstrated in all tumors separately. In two tumors, MET correlated with the density of proliferating cells and vessel cell density. There were no significant correlations between MET uptake and rCBV, and between rCBV and histological cell markers.

CONCLUSIONS: The MET uptake in hot spots, outside hotspots, and in infiltrating tumor edges unanimously reflects tumor cell density. The correlation between MET uptake and vessel density and density of proliferating cells is less stringent in infiltrating tumor edges and is probably more susceptible to artifacts caused by larger blood vessels surrounding the tumor. Although based on a limited number of samples, this study provides histological proof for MET as an indicator of tumor cell density and for the lack of statistically significant correlations between rCBV and histological cell markers in oligodendrogliomas.

Keywords
11C-methionine PET, Co-registration, Perfusion MR, Proliferation, Vascularization
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-357422 (URN)10.1007/s00259-018-4107-z (DOI)30109401 (PubMedID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-12-05Bibliographically approved
Falk Delgado, A., Fahlström, M., Nilsson, M., Berntsson, S. G., Zetterling, M., Libard, S., . . . Larsson, E.-M. (2017). Diffusion kurtosis imaging of gliomas grades II and III: a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation. Radiology and Oncology, 51(2), 121-129
Open this publication in new window or tab >>Diffusion kurtosis imaging of gliomas grades II and III: a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation
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2017 (English)In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 51, no 2, p. 121-129Article in journal (Refereed) Published
Abstract [en]

Background. Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas).

Patients and methods. Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves.

Results. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=< 0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815.

Conclusions. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.

Keywords
diffusion kurtosis imaging (DKI), glioma, perilesional, tumor infiltration, grade, subtype
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-323762 (URN)10.1515/raon-2017-0010 (DOI)000401697000001 ()
Funder
Swedish Cancer Society
Available from: 2017-06-09 Created: 2017-06-09 Last updated: 2017-06-09Bibliographically approved
Duffau, H., Mandonnet, E., Pallud, J., Krieg, S., Gil Robles, S., Hamer, P. d., . . . Blonski, M. (2017). Evidenced-based medicine in glioma: molecular biology is only part of the story [Letter to the editor]. The Lancet Oncology, 18(8), E429-E429
Open this publication in new window or tab >>Evidenced-based medicine in glioma: molecular biology is only part of the story
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2017 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, no 8, p. E429-E429Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-341857 (URN)10.1016/S1470-2045(17)30510-7 (DOI)000406301500005 ()
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-02-19Bibliographically approved
Zetterling, M., Berhane, L., Alafuzoff, I., Jakola, A. S. & Smits, A. (2017). Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases. PLoS ONE, 12(11), Article ID e0188419.
Open this publication in new window or tab >>Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, article id e0188419Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In the 2016 WHO classification, the diagnosis of oligodendroglioma has been restricted to IDH mutated, 1p19q codeleted tumors (IDHmut-codel). IDHmut oligoastrocytoma is now classified either as oligodendroglioma or astrocytoma based on presence of 1p19q codeletion. There is growing evidence that this molecular classification more closely reflects patient outcome. Due to the strong association between IDHmut-codel with oligodendroglial morphology, the additional impact of these markers on prognostic accuracy is largely unknown. Our aim was to assess the prognostic impact of IDHmut-codel in an unselected cohort of morphologically classified oligodendroglial tumors.

METHODS: We performed a retrospective chart review of oligodendroglial tumors (WHO grade II and III) operated since 1983. A total of 214 tumors were included, and molecular information was available for 96 tumors. The prognostic impact of IDHmut-codel together with clinical parameters was analyzed by multivariate Cox regression.

RESULTS: IDHmut-codel was registered in 64 tumors while for 150 tumors the molecular profile was negative for IDHmut-codel, unknown or incomplete. Comparison between the two groups showed that patients with IDHmut-codel tumors were younger (42 vs. 48 years), had more frequent frontal tumor location (48 vs. 33%) and presented more often with seizures (72 vs. 51%) and no signs of neurological impairment (14 vs. 30%) than patients harboring tumors with unknown or incomplete molecular profile. Multivariate survival analysis identified young age (HR 1.78 ≥ 40 years), the absence of neurological deficits or personality changes (HR 0.57), frontal tumor location (HR 0.64) and the presence of IDHmut-codel (HR 0.50) as independent predictors for longer survival, whereas tumor grade was not.

CONCLUSION: In this unselected single-institution cohort, the presence of IDHmut-codel was associated with more beneficial clinical parameters and was identified as an independent prognostic factor. We conclude that the classical oligodendroglioma genotype provides additional prognostic data beyond clinical characteristics, morphology and tumor grade.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-335342 (URN)10.1371/journal.pone.0188419 (DOI)000416484900035 ()29186201 (PubMedID)
Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2018-03-07Bibliographically approved
Rofes, A., Mandonnet, E., Godden, J., Baron, M. H., Colle, H., Darlix, A., . . . Wager, M. (2017). Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.. Acta Neurochirurgica, 159(7), 1167-1178
Open this publication in new window or tab >>Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.
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2017 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 159, no 7, p. 1167-1178Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years.

METHOD: A general survey on the managing of diffuse low-grade gliomas was answered by 21 centres in 11 European countries. Here we focused on specific questions regarding perioperative and intraoperative cognitive assessments.

RESULTS: More centres referred to the same speech and language therapist and/or neuropsychologist across all assessments; a core of assessment tools was routinely used across centres; fluency tasks were commonly used in the perioperative stages, and object naming during surgery; tasks that tapped on attention, executive functions, visuospatial awareness, calculation and emotions were sparsely administered; preoperative assessments were performed 1 month or 1 week before surgery; timing for postoperative assessments varied; finally, more centres recommended early rehabilitation, whenever needed.

CONCLUSIONS: There is an emerging trend towards following similar practices for the management of low-grade gliomas in Europe. Our results are descriptive and formalise current discussions in our group. Also, they contribute towards the development of a European assessment protocol.

Keywords
Assessment, Cognition, Diffuse low-grade glioma, Protocol, Surgery, Survey
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-321531 (URN)10.1007/s00701-017-3192-2 (DOI)000403508400001 ()28474122 (PubMedID)
Available from: 2017-05-08 Created: 2017-05-08 Last updated: 2017-09-14Bibliographically approved
Mandonnet, E., Wager, M., Almairac, F., Baron, M.-H., Blonski, M., Freyschlag, C. F., . . . Duffau, H. (2017). Survey on current practice within the European Low-Grade Glioma Network: where do we stand and what is the next step?. NEURO-ONCOLOGY PRACTICE, 4(4), 241-247
Open this publication in new window or tab >>Survey on current practice within the European Low-Grade Glioma Network: where do we stand and what is the next step?
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2017 (English)In: NEURO-ONCOLOGY PRACTICE, ISSN 2054-2577, Vol. 4, no 4, p. 241-247Article in journal (Refereed) Published
Abstract [en]

Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2017
Keywords
diffuse low-grade glioma, evidence-based medicine, GLIOCOM, surgery, survey
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-347266 (URN)10.1093/nop/npw031 (DOI)000424543500006 ()
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-03-28Bibliographically approved
Zetterling, M., Roodakker, K. R., Berntsson, S. G., Edqvist, P.-H. D., Latini, F., Landtblom, A.-M., . . . Smits, A. (2016). Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data. Journal of Neurosurgery, 125(5), 1155-1166
Open this publication in new window or tab >>Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data
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2016 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 125, no 5, p. 1155-1166Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed. METHODS Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices. RESULTS Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H-positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences. CONCLUSIONS The authors present a new method for the coregistration of histological and radiological characteristics of en bloc-removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.

Keywords
diffuse low-grade glioma; magnetic resonance imaging; tumor border; tumor cell infiltration; oncology
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-281052 (URN)10.3171/2015.10.JNS15583 (DOI)000386106100013 ()26918468 (PubMedID)
Available from: 2016-03-17 Created: 2016-03-17 Last updated: 2018-08-08Bibliographically approved
Falk Delgado, A., Nilsson, M., Latini, F., Mårtensson, J., Zetterling, M., Berntsson, S. G., . . . Larsson, E.-M. (2016). Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study. Radiology Research and Practice, Article ID 7671854.
Open this publication in new window or tab >>Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study
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2016 (English)In: Radiology Research and Practice, ISSN 2090-1941, E-ISSN 2090-195X, article id 7671854Article in journal (Refereed) Published
Abstract [en]

Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-294444 (URN)10.1155/2016/7671854 (DOI)000375303700001 ()27190647 (PubMedID)
Available from: 2016-05-20 Created: 2016-05-20 Last updated: 2017-11-30Bibliographically approved
Smits, A., Zetterling, M., Lundin, M., Melin, B., Fahlström, M., Grabowska, A., . . . Berntsson, S. G. (2015). Neurological Impairment Linked with Cortico-Subcortical Infiltration of Diffuse Low-Grade Gliomas at Initial Diagnosis Supports Early Brain Plasticity. Frontiers in Neurology, 6, Article ID 137.
Open this publication in new window or tab >>Neurological Impairment Linked with Cortico-Subcortical Infiltration of Diffuse Low-Grade Gliomas at Initial Diagnosis Supports Early Brain Plasticity
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2015 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 6, article id 137Article in journal (Refereed) Published
Abstract [en]

Diffuse low-grade gliomas (DLGG) are slow-growing brain tumors that in spite of an indolent behavior at onset show a continuous expansion over time and inevitably transform into malignant gliomas. Extensive tumor resections may be performed with preservation of neurological function due to neuroplasticity that is induced by the slow tumor growth. However, DLGG prefer to migrate along subcortical pathways, and white matter plasticity is considerably more limited than gray matter plasticity. Whether signs of functional decompensating white matter that may be found as early as at disease presentation has not been systematically studied. Here, we examined 52 patients who presented with a DLGG at the time of radiological diagnosis. We found a significant correlation between neurological impairment and eloquent cortico-subcortical tumor localization, but not between neurological function and tumor volume. These results suggest that even small tumors invading white matter pathways may lack compensatory mechanisms for functional reorganization already at disease presentation.

Keywords
low-grade gliomas; neurological function; professional situation; tumor volume; tumor location; brain plasticity; radiological diagnosis
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-257072 (URN)10.3389/fneur.2015.00137 (DOI)000363847800001 ()26113841 (PubMedID)
Available from: 2015-06-29 Created: 2015-06-29 Last updated: 2017-12-04Bibliographically approved
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