Imaging findings following regorafenib in malignant gliomas: FET PET adds valuable information to anatomical MRI.
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ABSTRACT:
SUBMITTER: Galldiks N
PROVIDER: S-EPMC7212846 | biostudies-literature | 2019 May-Dec
REPOSITORIES: biostudies-literature
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Imaging findings following regorafenib in malignant gliomas: FET PET adds valuable information to anatomical MRI.
Galldiks Norbert N Werner Jan-Michael JM Tscherpel Caroline C Fink Gereon R GR Langen Karl-Josef KJ
Neuro-oncology advances 20190501 1
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Project description:Mutations in the isocitrate dehydrogenase (IDH mut) gene have gained paramount importance for the prognosis of glioma patients. To date, reliable techniques for a preoperative evaluation of IDH genotype remain scarce. Therefore, we investigated the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET radiomics using textural features combined with static and dynamic parameters of FET uptake for noninvasive prediction of IDH genotype. Prior to surgery, 84 patients with newly diagnosed and untreated gliomas underwent FET PET using a standard scanner (15 of 56 patients with IDH mut) or a dedicated high-resolution hybrid PET/MR scanner (11 of 28 patients with IDH mut). Static, dynamic and textural parameters of FET uptake in the tumor area were evaluated. Diagnostic accuracy of the parameters was evaluated using the neuropathological result as reference. Additionally, FET PET and textural parameters were combined to further increase the diagnostic accuracy. The resulting models were validated using cross-validation. Independent of scanner type, the combination of standard PET parameters with textural features increased significantly diagnostic accuracy. The highest diagnostic accuracy of 93% for prediction of IDH genotype was achieved with the hybrid PET/MR scanner. Our findings suggest that the combination of conventional FET PET parameters with textural features provides important diagnostic information for the non-invasive prediction of the IDH genotype.
| S-EPMC6127131 | biostudies-literature
Project description:PurposeGlioma treatment planning requires precise tumor delineation, which is typically performed with contrast-enhanced (CE) MRI. However, CE MRI fails to reflect the entire extent of glioma. O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET may detect tumor volumes missed by CE MRI. We investigated the clinical value of simultaneous FET-PET and CE MRI in delineating tumor extent before treatment planning. Guided stereotactic biopsy was used to validate the findings.MethodsConventional MRI and 18F-FET PET were performed simultaneously on a hybrid PET/MR in 33 patients with histopathologically confirmed glioma. Tumor volumes were quantified using a tumor-to-brain ratio ≥ 1.6 (VPET) and a visual threshold (VCE). We visually assessed abnormal areas on FLAIR images and calculated Dice's coefficient (DSC), overlap volume (OV), discrepancy-PET, and discrepancy-CE. Additionally, several stereotactic biopsy samples were taken from "matched" or "mismatched" FET-PET and CE MRI regions.ResultsAmong 31 patients (93.94%), FET-PET delineated significantly larger tumor volumes than CE MRI (77.84 ± 51.74 cm3 vs. 34.59 ± 27.07 cm3, P < 0.05). Of the 21 biopsy samples obtained from regions with increased FET uptake, all were histopathologically confirmed as glioma tissue or tumor infiltration, whereas only 13 showed enhancement on CE MRI. Among all patients, the spatial similarity between VPET and VCE was low (average DSC 0.56 ± 0.22), while the overlap was high (average OV 0.95 ± 0.08). The discrepancy-CE and discrepancy-PET were lower than 10% in 28 and 0 patients, respectively. Eleven patients showed VPET partially beyond abnormal signal areas on FLAIR images.ConclusionThe metabolically active biodistribution of gliomas delineated with FET-PET significantly exceeds tumor volume on CE MRI, and histopathology confirms these findings. Our preliminary results indicate that combining the anatomic and molecular information obtained from conventional MRI and FET-PET would reveal a more accurate glioma extent, which is critical for individualized treatment planning.
| S-EPMC7188715 | biostudies-literature
Project description:IntroductionBrain and central nervous system (CNS) tumors are the second most common cancer type in children and adolescents. Positron emission tomography (PET) imaging with radiolabeled amino acids visualizes the amino acid uptake in brain tumor cells compared with the healthy brain tissue, which provides additional information over magnetic resonance imaging (MRI) for differential diagnosis, treatment planning, and the differentiation of tumor relapse from treatment-related changes. However, tumor delineation is a time-consuming task subject to inter-rater variability. We propose a deep learning method for the automatic delineation of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET PET) pediatric CNS tumors.MethodsA total of 109 [18F]FET PET and MRI scans from 66 pediatric patients with manually delineated reference were included. We trained an artificial neural network (ANN) for automatic delineation and compared its performance against the manual reference on delineation accuracy and subsequent clinical metric accuracy. For clinical metrics, we extracted the biological tumor volume (BTV) and tumor-to-background mean and max (TBRmean and TBRmax).ResultsThe ANN produced high tumor overlap (median dice-similarity coefficient [DSC] of 0.93). The clinical metrics extracted with the manual reference and the ANN were highly correlated (r ≥ 0.99). The spatial location of TBRmax was identical in almost all cases (96%). The ANN and the manual reference produced similar changes in the clinical metrics between baseline and follow-up scans.ConclusionThe proposed ANN achieved high concordance with the manual reference and may be an important tool for decision aid, limiting inter-reader variance and improving longitudinal evaluation in clinical routine, and for future multicenter studies of pediatric CNS tumors.
| S-EPMC11440972 | biostudies-literature
Project description:BackgroundWe aimed to elucidate the place of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in prognostic models of gadolinium (Gd)-negative gliomas.MethodsIn 98 patients with Gd-negative gliomas undergoing 18F-FET PET guided biopsy, time activity curves (TACs) of each tumor were qualitatively categorized as either increasing or decreasing. Additionally, post-hoc quantitative analyses were done using minimal time-to-peak (TTPmin) measurements. Prognostic factors were obtained from multivariate hazards models. The fit of the biospecimen- and imaging-derived models was compared.ResultsA homogeneous increasing, mixed, and homogeneous decreasing TAC pattern was seen in 51, 19, and 28 tumors, respectively. Mixed TAC tumors exhibited both increasing and decreasing TACs. Corresponding adjusted 5-year survival was 85%, 47%, and 19%, respectively (P < 0.001). Qualitative and quantitative TAC measurements were highly intercorrelated (P < 0.0001). TTPmin was longest (shortest) in the homogeneous increasing (decreasing) TAC group and in between in the mixed TAC group. TTPmin was longer in isocitrate dehydrogenase (IDH)-mutant tumors (P < 0.001). Outcome was similarly precisely predicted by biospecimen- and imaging-derived models. In the biospecimen model, World Health Organization (WHO) grade (P < 0.0001) and IDH status (P < 0.001) were predictors for survival. Outcome of homogeneous increasing (homogeneous decreasing) TAC tumors was nearly identical, with both TTPmin > 25 min (TTPmin ≤ 12.5 min) tumors and IDH-mutant grade II (IDH-wildtype) gliomas. Outcome of mixed TAC tumors matched that of both intermediate TTPmin (>12.5 min and ≤25 min) and IDH-mutant, grade III gliomas. Each of the 3 prognostic clusters differed significantly from the other ones of the respective models (P < 0.001).ConclusionTAC measurements constitute a powerful biomarker independent from tumor grade and IDH status.
| S-EPMC6374762 | biostudies-literature
Project description:BackgroundThe aim of this study was to investigate the potential of combined textural feature analysis of contrast-enhanced MRI (CE-MRI) and static O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation between local recurrent brain metastasis and radiation injury since CE-MRI often remains inconclusive.MethodsFifty-two patients with new or progressive contrast-enhancing brain lesions on MRI after radiotherapy (predominantly stereotactic radiosurgery) of brain metastases were additionally investigated using FET PET. Based on histology (n = 19) or clinicoradiological follow-up (n = 33), local recurrent brain metastases were diagnosed in 21 patients (40%) and radiation injury in 31 patients (60%). Forty-two textural features were calculated on both unfiltered and filtered CE-MRI and summed FET PET images (20-40 min p.i.), using the software LIFEx. After feature selection, logistic regression models using a maximum of five features to avoid overfitting were calculated for each imaging modality separately and for the combined FET PET/MRI features. The resulting models were validated using cross-validation. Diagnostic accuracies were calculated for each imaging modality separately as well as for the combined model.ResultsFor the differentiation between radiation injury and recurrence of brain metastasis, textural features extracted from CE-MRI had a diagnostic accuracy of 81% (sensitivity, 67%; specificity, 90%). FET PET textural features revealed a slightly higher diagnostic accuracy of 83% (sensitivity, 88%; specificity, 75%). However, the highest diagnostic accuracy was obtained when combining CE-MRI and FET PET features (accuracy, 89%; sensitivity, 85%; specificity, 96%).ConclusionsOur findings suggest that combined FET PET/CE-MRI radiomics using textural feature analysis offers a great potential to contribute significantly to the management of patients with brain metastases.
| S-EPMC6118093 | biostudies-literature
Project description:(1) Background: The phase 2 Regorafenib in Relapsed Glioblastoma (REGOMA) trial indicated a survival benefit for patients with first recurrence of a glioblastoma when treated with the multikinase inhibitor regorafenib (REG) instead of lomustine. The aim of this retrospective study was to investigate REG penetration to cerebrospinal fluid (CSF), treatment efficacy, and effects on magnetic resonance imaging (MRI) in patients with recurrent high-grade gliomas. (2) Methods: Patients were characterized by histology, adverse events, steroid treatment, overall survival (OS), and MRI growth pattern. REG and its two active metabolites were quantified by liquid chromatography/tandem mass spectrometry in patients' serum and CSF. (3) Results: 21 patients mainly with IDH-wildtype glioblastomas who had been treated with REG were retrospectively identified. Thirteen CFS samples collected from 3 patients of the cohort were available for pharmacokinetic testing. CSF levels of REG and its metabolites were significantly lower than in serum. Follow-up MRI was available in 19 patients and showed progressive disease (PD) in all but 2 patients. Two distinct MRI patterns were identified: 7 patients showed classic PD with progression of contrast enhancing lesions, whereas 11 patients showed a T2-dominant MRI pattern characterized by a marked reduction of contrast enhancement. Median OS was significantly better in patients with a T2-dominant growth pattern (10 vs. 27 weeks respectively, p = 0.003). Diffusion restrictions were observed in 13 patients. (4) Conclusion: REG and its metabolites were detectable in CSF. A distinct MRI pattern that might be associated with an improved OS was observed in half of the patient cohort. Treatment response in the total cohort was poor.
| S-EPMC6947028 | biostudies-literature
Project description:ObjectiveTo compare the presence of post-operative residual disease by magnetic resonance imaging (MRI) and [18F]fluorothymidine (FLT)-positron emission tomography (PET)-computer tomography (CT) in patients with malignant glioma and to estimate the impact of 18F-FLT PET on the delineation of post-operative target volumes for radiotherapy (RT) planning.MethodsNineteen patients with post-operative residual malignant gliomas were enrolled in this study. For each patient, 18F- FLT PET-CT and MRI were acquired in the same week, within 4 weeks after surgery but before the initiation of RT. The PET-CT and MRI data were co-registered based on mutual information. The residual tumor volume defined on the 18F-FLT PET (Vol-PET) was compared with that of gadolinium [Gd] enhancement on T1-weighted MRI (Vol-T1) and areas of hyperintensity on T2-weighted MRI (Vol-T2).ResultsThe mean Vol-PET (14.61 cm3) and Vol-T1 (13.60 cm3) were comparable and smaller than the mean Vol-T2 (32.93 cm3). The regions of 18F-FLT uptake exceeded the contrast enhancement and the hyperintense area on the MRI in 14 (73.68%) and 8 patients (42.11%), respectively. In 5 (26.32%) of the 19 patients, Vol-PET extended beyond 25 mm from the margin of Vol-T1; in 2 (10.53%) patients, Vol-PET extended 20 mm from the margin of Vol-T2. Vol-PET was detected up to 35 mm away from the edge of Vol-T1 and 24 mm away from the edge of Vol-T2. In 16 (84.21%) of the 19 patients, the Vol-T1 extended beyond the Vol-PET. In all of the patients, at least some of the Vol-T2 was located outside of the Vol-PET.ConclusionsThe volumes of post-operative residual tumor in patients with malignant glioma defined by 18F-FLT uptake on PET are not always consistent with the abnormalities shown on post-operative MRI. Incorporation of 18F-FLT-PET in tumor delineation may have the potential to improve the definition of target volume in post-operative radiotherapy.
| S-EPMC4349865 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Damage to the blood-brain barrier with subsequent contrast enhancement is a hallmark of glioblastoma. Non-enhancing tumor invasion into the peritumoral edema is, however, not usually visible on conventional magnetic resonance imaging. New quantitative techniques using relaxometry offer additional information about tissue properties. The aim of this study was to evaluate longitudinal relaxation R1, transverse relaxation R2, and proton density in the peritumoral edema in a group of patients with malignant glioma before surgery to assess whether relaxometry can detect changes not visible on conventional images. METHODS:In a prospective study, 24 patients with suspected malignant glioma were examined before surgery. A standard MRI protocol was used with the addition of a quantitative MR method (MAGIC), which measured R1, R2, and proton density. The diagnosis of malignant glioma was confirmed after biopsy/surgery. In 19 patients synthetic MR images were then created from the MAGIC scan, and ROIs were placed in the peritumoral edema to obtain the quantitative values. Dynamic susceptibility contrast perfusion was used to obtain cerebral blood volume (rCBV) data of the peritumoral edema. Voxel-based statistical analysis was performed using a mixed linear model. RESULTS:R1, R2, and rCBV decrease with increasing distance from the contrast-enhancing part of the tumor. There is a significant increase in R1 gradient after contrast agent injection (P < .0001). There is a heterogeneous pattern of relaxation values in the peritumoral edema adjacent to the contrast-enhancing part of the tumor. CONCLUSION:Quantitative analysis with relaxometry of peritumoral edema in malignant gliomas detects tissue changes not visualized on conventional MR images. The finding of decreasing R1 and R2 means shorter relaxation times closer to the tumor, which could reflect tumor invasion into the peritumoral edema. However, these findings need to be validated in the future.
| S-EPMC5441583 | biostudies-literature
Project description:BACKGROUND:Radiolabeled prostate-specific membrane antigen PSMA-based PET/CT or PET/MRI is a whole-body imaging technique currently performed for the detection of prostate cancer lesions. PSMA has been also demonstrated to be expressed by the neovasculature of many other solid tumors. OBJECTIVE:The aim of this review is to evaluate the possible diagnostic role of radiolabeled PSMA PET/CT or PET/MRI in patients with gliomas and glioblastomas, by summarizing the available literature data. METHODS:A comprehensive literature search of the PubMed/MEDLINE, Scopus, Embase and Cochrane library databases was conducted to find relevant published articles about the diagnostic performance of radiolabeled PSMA binding agents in PET/CT or PET/MRI imaging of patients with suspected gliomas or glioblastomas. RESULTS:Seven case reports or case series and 3 studies enrolling more than 10 patients showed that gliomas and glioblastoma are PSMA-avid tumors. CONCLUSION:Radiolabeled PSMA imaging seems to be useful in analyzing glioma/glioblastoma. Further studies enrolling a wider population are needed to clarify the real clinical and diagnostic role of radiolabeled PSMA in this setting and its possible position in the diagnostic flow-chart.
| S-EPMC7527542 | biostudies-literature
Project description:BackgroundTumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as positron emission tomography (PET) imaging.ObjectivesThis study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity.Materials and methodsSeventeen patients harboring HGGs underwent a pre-operative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats' spatial distribution, quantitative features and histopathological characteristics were analyzed.ResultsA highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend toward a higher representation of the most aggressive clusters in WHO (World Health Organization) grade IV compared to WHO III was observed.ConclusionPreliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.
| S-EPMC9326318 | biostudies-literature