Reconstruction of the Corticospinal Tract in Patients with Motor-Eloquent High-Grade Gliomas Using Multilevel Fiber Tractography Combined with Functional Motor Cortex Mapping.

BACKGROUND AND PURPOSE: Tractography of the corticospinal tract is paramount to presurgical planning and guidance of intraoperative resection in patients with motor-eloquent gliomas. It is well-known that DTI-based tractography as the most frequently used technique has relevant shortcomings, particularly for resolving complex fiber architecture. The purpose of this study was to evaluate multilevel fiber tractography combined with functional motor cortex mapping in comparison with conventional deterministic tractography algorithms. MATERIALS AND METHODS: Thirty-one patients (mean age, 61.5 [SD, 12.2] years) with motor-eloquent high-grade gliomas underwent MR imaging with DWI (TR/TE = 5000/78 ms, voxel size = 2 × 2 × 2 mm3, 1 volume at b = 0 s/mm2, 32 volumes at b = 1000 s/mm2). DTI, constrained spherical deconvolution, and multilevel fiber tractography-based reconstruction of the corticospinal tract within the tumor-affected hemispheres were performed. The functional motor cortex was enclosed by navigated transcranial magnetic stimulation motor mapping before tumor resection and used for seeding. A range of angular deviation and fractional anisotropy thresholds (for DTI) was tested. RESULTS: For all investigated thresholds, multilevel fiber tractography achieved the highest mean coverage of the motor maps (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold = 71.8%, 22.6%, and 11.7%) and the most extensive corticospinal tract reconstructions (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold = 26,485 mm3, 6308 mm3, and 4270 mm3). CONCLUSIONS: Multilevel fiber tractography may improve the coverage of the motor cortex by corticospinal tract fibers compared with conventional deterministic algorithms. Thus, it could provide a more detailed and complete visualization of corticospinal tract architecture, particularly by visualizing fiber trajectories with acute angles that might be of high relevance in patients with gliomas and distorted anatomy.

Methylation subgroup and molecular heterogeneity is a hallmark of glioblastoma: implications for biopsy targeting, classification and therapy.

BACKGROUND: Intratumoral heterogeneity at the cellular and molecular level is a hallmark of glioblastoma (GB) that contributes to treatment resistance and poor clinical outcome. Little is known regarding epigenetic heterogeneity and intratumoral phylogeny and their implication for molecular classification and targeted therapies. PATIENTS AND METHODS: Multiple tissue biopsies (238 in total) were sampled from 56 newly-diagnosed, treatment-naive GB patients from a prospective in-house cohort and publicly available data and profiled for DNA methylation using the Illumina MethylationEPIC array. Methylation-based classification using the glioma classifier developed by Ceccarelli et al. and estimation of the MGMT promoter methylation status via the MGMT-STP27 model were carried out. In addition, copy number variations (CNVs) and phylogeny were analyzed. RESULTS: Almost half of the patients (22/56, 39%) harbored tumors composed of heterogeneous methylation subtypes. We found two predominant subtype combinations: classic-/mesenchymal-like, and mesenchymal-/pilocytic astrocytoma-like. Nine patients (16%) had tumors composed of subvolumes with and without MGMT promoter methylation, whereas 20 patients (36%) were homogeneously methylated, and 27 patients (48%) were homogeneously unmethylated. CNV analysis revealed high variations in many genes, including CDKN2A/B, EGFR, and PTEN. Phylogenetic analysis correspondingly showed a general pattern of CDKN2A/B loss and gain of EGFR, PDGFRA, and CDK4 during early stages of tumor development. CONCLUSIONS: (Epi)genetic intratumoral heterogeneity is a hallmark of GB, both at DNA methylation and CNV level. This intratumoral heterogeneity is of utmost importance for molecular classification as well as for defining therapeutic targets in this disease, as single biopsies might underestimate the true molecular diversity in a tumor.

Fully automated analysis combining [18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression.

PURPOSE: To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. MATERIAL AND METHODS: At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier's performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. RESULTS: In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77-0.93 (sensitivity 0.91, 95% CI 0.81-0.97; specificity 0.71, 95% CI 0.44-0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72-0.9), 0.81 for [18F]-FET-PET (95% CI 0.7-0.89), and 0.81 for expert consensus (95% CI 0.7-0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. CONCLUSION: Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.

Optimal classification of long echo time in vivo magnetic resonance spectra in the detection of recurrent brain tumors.

We describe the optimal high-level postprocessing of single-voxel (1)H magnetic resonance spectra and assess the benefits and limitations of automated methods as diagnostic aids in the detection of recurrent brain tumor. In a previous clinical study, 90 long-echo-time single-voxel spectra were obtained from 52 patients and classified during follow-up (30/28/32 normal/non-progressive tumor/tumor). Based on these data, a large number of evaluation strategies, including both standard resonance line quantification and algorithms from pattern recognition and machine learning, were compared in a quantitative evaluation. Results from linear and non-linear feature extraction, including ICA, PCA and wavelet transformations, and also the data from resonance line quantification were combined systematically with different classifiers such as LDA, chemometric methods (PLS, PCR), support vector machines and ensemble methods. Classification accuracy was assessed using a leave-one-out cross-validation scheme and the area under the curve (AUC) of the receiver operator characteristic (ROC). A regularized linear regression on spectra with binned channels reached 91% classification accuracy compared with 83% from quantification. Interpreting the loadings of these regressions, we find that lipid and lactate signals are too unreliable to be used in a simple machine rule. Choline and NAA are the main source of relevant information. Overall, we find that fully automated pattern recognition algorithms perform as well as, or slightly better than, a manually controlled and optimized resonance line quantification.

[Further development of the International Pneumoconiosis Classification--from ILO 1980 to ILO 2000 and to ILO 2000/German Federal Republic version]. / Die Weiterentwicklung der Internationalen Staublungenklassifikation - von der ILO 1980 zur ILO 2000 und zur ILO 2000/Version Bundesrepublik Deutschland.

The ILO (1980) Classification has been revised during recent years. The new version is now available as the International Classification of Radiographs of Pneumoconioses (Revised edition 2000). The Guidelines booklet is currently available only in English. Those involved felt it was important to maintain continuity with the ILO (1980) edition, in particular to retain the standard radiographs, despite their restricted quality, so as to ensure comparability with earlier national and international data sets. The standard films illustrating pleural abnormalities, and 'u'-shadows, have been modified and reconstituted. The most important changes relate to assessment of film quality, pleural abnormalities, and additional symbols. In Germany, film quality is characterised as "+", "+-", "+--" and "u" according to whether the ability to assess pneumoconiosis is judged to be unimpeachable ("+") to unusable ("u"). If a film is not classified as "+", then written comments regarding defects are required. For "diffuse" pleural thickening, the ILO (2000) edition now requires the presence also of obliteration of the costophrenic angle. This was not required in the earlier (1980) edition and, as previously, is also not stipulated in the German version. A minimum width of 3 mm (previously 0-5 mm), coded "a", is required both for plaques as well as for the margin to the lateral chest wall. Congruence is thus achieved for criteria, which, in German practice, lead to an indication of suspect occupational disease. Plaques on the diaphragm are not considered for measurement of extent; they are only coded as present or absent. If calcification is identified, then this must also be classified and measured as a localised plaque. Extent of calcification on its own, previously coded "0" to "3", is no longer specified. The following new symbols, illustrated by new diagrams, have been introduced: aa = atherosclerotic aorta; at = apical thickening; cg = calcified granuloma (or other non-pneumocononiotic nodules); me = mesothelioma (already previously differentiated from "ca" on the German record sheet); pa = plate atelectasis; pb= parenchymal bands; ra = rounded atelectasis; od = other disease. (Examples of the latter are illustrated diagrammatically by lobar pneumonia, aspergilloma, goiter and hiatal hernia.) Earlier national differences (ILO 1980/German Federal Republic) on particular issues have also been agreed among German "double-readers" ["Zweitbeurteiler"]. However, conformity between the original (ILO 2000) text and the national (German) modified text has been retained in large measure. The detailed descriptions of the standard films differ in certain respects from the German (1980) definitions. Some revision of individual descriptions of the films are proposed. Except for a few differences, agreement was reached here too. The definitive date for the change in Germany is expected to be in early 2004. The standard films are already available now through ILO offices in Geneva or Bonn (addresses in appendix.)

Asbestos-related diseases and asbestos types used in the former GDR.

In the period from 1960 to 1990 about 1.4 million tonnes of asbestos were imported by the former German Democratic Republic (GDR) and mainly processed into asbestos-cement products for the building industry. The production was concentrated in the former counties of Magdeburg and Dresden. In the past, asbestos was primarily used as insulation and fire prevention material, etc. in the large-scale chemical industry. Chrysotile was predominantly imported from the former Soviet Union, partly from Canada. Very small amounts of amphiboles came from Mozambique, but they were not processed in the counties of Magdeburg and Halle. In the German Federal State of Saxony-Anhalt, approx. 600 asbestoses, almost 2,700 pleural changes caused by asbestos, 843 asbestos-induced mesotheliomas and 787 bronchial and laryngeal carcinomas caused by asbestos were recorded in the period from 1960 to 1990. A considerable percentage of the mesotheliomas are solely due to exposure to chrysotile asbestos.

Use of asbestos, health risks and induced occupational diseases in the former East Germany.

In the period from 1960 to 1990 about 1.4 million tons of asbestos were imported and mainly processed into asbestos-cement products for the building industry. The production was concentrated in the former countries of Magdeburg and Dresden. In the past asbestos was primarily used as insulation and fire prevention material, etc. in the large-scale chemical industry. The asbestos was imported from the former Soviet Union, smaller amounts came from Canada. In the German Federal State of Saxony-Anhalt, approximately 600 asbestoses, almost 2700 pleural changes caused by asbestos, 843 asbestos-induced mesotheliomas and 787 bronchial and laryngeal carcinomas were recorded in the period from 1960 to 1990. A considerable percentage of the mesotheliomas are solely due to exposure to chrysotile asbestos.