Background
In glioma patients, multimodality therapy and recurrent tumor can lead to structural brain tissue damage characterized by pathologic findings in MR and PET imaging. However, little is ...known about the impact of different types of damage on the fiber architecture of the affected white matter.
Patients and methods
This study included 121 pretreated patients (median age, 52 years; ECOG performance score, 0 in 48%, 1-2 in 51%) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median follow-up time of 14 months (range, 1-214 months), anatomic MR and O-(2-
18
Ffluoroethyl)-L-tyrosine (FET) PET images were acquired on a 3T hybrid PET/MR scanner. Post-therapeutic findings comprised resection cavities, regions with contrast enhancement or increased FET uptake and T2/FLAIR hyperintensities. Local fiber density was determined from high angular-resolution diffusion-weighted imaging and advanced tractography methods. A cohort of 121 healthy subjects selected from the 1000BRAINS study matched for age, gender and education served as a control group.
Results
Lesion types differed in both affected tissue volumes and relative fiber densities compared to control values (resection cavities: median volume 20.9 mL, fiber density 16% of controls; contrast-enhanced lesions: 7.9 mL, 43%; FET uptake areas: 30.3 mL, 49%; T2/FLAIR hyperintensities: 53.4 mL, 57%, p<0.001). In T2/FLAIR-hyperintense lesions caused by peritumoral edema due to recurrent glioma (n=27), relative fiber density was as low as in lesions associated with radiation-induced gliosis (n=13, 48% vs. 53%, p=0.17). In regions with pathologically increased FET uptake, local fiber density was inversely related (p=0.005) to the extent of uptake. Total fiber loss associated with contrast-enhanced lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on overall ECOG score.
Conclusions
These results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients’ performance status due to the larger volume affected.
Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in O6-methylguanine-DNA methyltransferase ...(MGMT) promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified response assessment in neuro-oncology (RANO) criteria of 2017.
Patients with ≥ 3 follow-up MRIs were included. Preliminary PD was defined as a ≥ 25% increase of the sum of products of perpendicular diameters (SPD) of a new or increasing lesion compared to baseline. PD required a second ≥25% increase of the SPD. Treatment-associated changes require stable or regressing disease after preliminary PD.
Of the 424 evaluable patients, 221 patients (52%) were randomized into the cilengitide and 203 patients (48%) into the control arm. After chemoradiation with or without cilengitide, preliminary PD occurred in 274 patients (65%) during available follow-up, and 88 of these patients (32%) had treatment-associated changes, whereas 67 patients (25%) had PD. The remaining 119 patients (43%) had no further follow-up after preliminary PD. Treatment-associated changes were more common in the cilengitide arm than in the standard-of-care arm (24% vs. 17%; relative risk, 1.3; 95% CI, 1.004-1.795; P = .047). Treatment-associated changes occurred mainly during the first 6 months after RT (54% after 3 months vs. 13% after 6 months).
With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in MGMT promoter-methylated glioblastoma. This rate was higher after cilengitide compared to standard-of-care treatment. Confirmatory scans, as recommended in the modified RANO criteria, were not always available reflecting current clinical practice.
Abstract
BACKGROUND
Glioma patients frequently suffer from cognitive dysfunction potentially caused by tumor invasion or treatment effects. We hypothesized that cognitive functioning in pretreated ...glioma patients critically depends on the maintained structural connectivity of multiple brain networks. PATIENTS AND
METHODS
The study included 121 pretreated glioma patients (median age, 52 years; median ECOG score, 1; CNS WHO grade, 3 or 4) who had biopsy or resection plus chemoradiation as first-line therapy. Cognitive performance was assessed by ten tests in five main cognitive domains after a median time of 14 months (range, 1-214 months) after treatment initiation. Hybrid amino acid PET/MRI using the tracer O-(2-18Ffluoroethyl)-L-tyrosine, a network-based cortical parcellation, and advanced tractography tools were used to generate whole-brain fiber count-weighted connectivity matrices. These matrices were applied to a machine learning-based model to identify predictive fiber connections, essential cortical nodes, and the networks underlying cognitive performance in the evaluated domains.
RESULTS
Compared to healthy controls (n=121), the cognitive scores were significantly lower in nine cognitive tests. For each test, a subset of connections between nodes (median number, 254; range, 32-542) was identified whose fiber count sum was related to the actual scores in a linear model (median R2, 0.37; range, 0.16-0.44). Leave-one-out cross-validation confirmed the model's generalizability in 7 of 10 tests (median correlation coefficient for predicted vs. observed scores, 0.47; range, 0.39-0.57). Critically involved cortical regions (≥ 10 adjacent predictive edges) included predominantly left-sided cortical nodes of the visual, somatomotor, dorsal/ventral attention, and default mode networks. Highly critical nodes (≥ 15-20 edges) included the default-mode network’s left temporal and bilateral posterior cingulate cortex.
CONCLUSION
These results suggest that the cognitive performance of pretreated glioma patients is strongly related to structural connectivity between multiple brain networks and depends on the integrity of known network hubs also involved in other neurological disorders.
Abstract PET imaging, particularly using amino acid tracers, has become a valuable adjunct to anatomical MRI in the clinical management of patients with glioma. Collaborative international efforts ...have led to the development of clinical and technical guidelines for PET imaging in gliomas. The increasing readiness of statutory health insurance agencies, especially in European countries, to reimburse amino acid PET underscores its growing importance in clinical practice. Integrating artificial intelligence and radiomics in PET imaging of patients with glioma may significantly improve tumor detection, segmentation, and response assessment. Efforts are ongoing to facilitate the clinical translation of these techniques. Considerable progress in computer technology developments (eg quantum computers) may be helpful to accelerate these efforts. Next-generation PET scanners, such as long-axial field-of-view PET/CT scanners, have improved image quality and body coverage and therefore expanded the spectrum of indications for PET imaging in Neuro-Oncology (eg PET imaging of the whole spine). Encouraging results of clinical trials in patients with glioma have prompted the development of PET tracers directing therapeutically relevant targets (eg the mutant isocitrate dehydrogenase) for novel anticancer agents in gliomas to improve response assessment. In addition, the success of theranostics for the treatment of extracranial neoplasms such as neuroendocrine tumors and prostate cancer has currently prompted efforts to translate this approach to patients with glioma. These advancements highlight the evolving role of PET imaging in Neuro-Oncology, offering insights into tumor biology and treatment response, thereby informing personalized patient care. Nevertheless, these innovations warrant further validation in the near future.
We present an autotuning approach for compile-time optimization of numerical discretization methods in simulations of partial differential equations. Our approach is based on data-driven regression ...of performance models for numerical methods. We use these models at compile time to automatically determine the parameters (e.g., resolution, time step size, etc.) of numerical simulations of continuum spatio-temporal models in order to optimize the tradeoff between simulation accuracy and runtime. The resulting autotuner is developed for the compiler of a Domain-Specific Language (DSL) for numerical simulations. The abstractions in the DSL enable the compiler to automatically determine the performance models and know which discretization parameters to tune. We demonstrate that this high-level approach can explore a large space of possible simulations, with simulation runtimes spanning multiple orders of magnitude. We evaluate our approach in two test cases: the linear diffusion equation and the nonlinear Gray-Scott reaction–diffusion equation. The results show that our model-based autotuner consistently finds configurations that outperform those found by state-of-the-art general-purpose autotuners. Specifically, our autotuner yields simulations that are on average 4.2x faster than those found by the best generic exploration algorithms, while using 16x less tuning time. Compared to manual tuning by a group of researchers with varying levels of expertise, the autotuner was slower than the best users by not more than a factor of 2, whereas it was able to significantly outperform half of them.
•Autotuning approach for compile-time optimization of numerical discretization methods.•Use of domain knowledge (convergence orders) to guide our search approach.•Model-based optimization technique outperformed general-purpose autotuning approaches.
Brain metastases in patients with extracranial cancer are typically associated with increased morbidity and mortality. Stereotactic radiotherapy and immunotherapy using checkpoint inhibitors ...currently are essential in brain metastases treatment. Since conventional contrast-enhanced MRI alone cannot reliably differentiate between treatment-induced changes and brain metastasis relapse, several studies investigated the role of PET imaging and, more recently, radiomics, based on routinely acquired PET images, to overcome this clinically relevant challenge.
The current literature on PET imaging, including radiomics, in patients with brain metastases, focusing on the diagnosis and assessment of post-treatment relapse, is summarized.
Available data suggest that imaging parameters, including radiomics features, mainly derived from amino acid PET, are helpful for diagnosis and assessment of post-treatment relapse in patients with brain metastases.
Purpose
In glioma patients, tumor development and multimodality therapy are associated with changes in health-related quality of life (HRQoL). It is largely unknown how different types and locations ...of tumor- and treatment-related brain lesions, as well as their relationship to white matter tracts and functional brain networks, affect HRQoL.
Methods
In 121 patients with pretreated gliomas of WHO CNS grades 3 or 4, structural MRI, O-(2-
18
Ffluoroethyl)-L-tyrosine (FET) PET, resting-state functional MRI (rs-fMRI) and self-reported HRQoL questionnaires (EORTC QLQ-C30/BN20) were obtained. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and lesions with pathologically increased FET uptake were delineated. Effects of tumor lateralization, involvement of white matter tracts or resting-state network nodes by different types of lesions and within-network rs-fMRI connectivity were analyzed in terms of their interaction with HRQoL scores.
Results
Right hemisphere gliomas were associated with significantly less favorable outcomes in physical, role, emotional and social functioning, compared with left-sided tumors. Most functional HRQoL scores correlated significantly with right-sided white-matter tracts involvement by T2/FLAIR hyperintensities and with loss of within-network functional connectivity of right-sided nodes. Tumors of the left hemisphere caused significantly more communication deficits.
Conclusion
In pretreated high-grade gliomas, right hemisphere lesions are associated with reduced HRQoL scores in most functional domains except communication ability, compared to tumors of the left hemisphere. These relationships are mainly observed for T2/FLAIR lesions involving structural and functional networks in the right hemisphere. The data suggest that sparing the right hemisphere from treatment-related tissue damage may improve HRQoL in glioma patients.
Abstract
Background
In glioma patients, tumor growth and subsequent treatments are associated with various types of brain lesions. We hypothesized that cognitive functioning in these patients ...critically depends on the maintained structural connectivity of multiple brain networks.
Methods
The study included 121 glioma patients (median age, 52 years; median Eastern Cooperative Oncology Group performance score 1; CNS-WHO Grade 3 or 4) after multimodal therapy. Cognitive performance was assessed by 10 tests in 5 cognitive domains at a median of 14 months after treatment initiation. Hybrid amino acid PET/MRI using the tracer O-(2-18Ffluoroethyl)-L-tyrosine, a network-based cortical parcellation, and advanced tractography were used to generate whole-brain fiber count-weighted connectivity matrices. The matrices were applied to a cross-validated machine-learning model to identify predictive fiber connections (edges), critical cortical regions (nodes), and the networks underlying cognitive performance.
Results
Compared to healthy controls (n = 121), patients’ cognitive scores were significantly lower in 9 cognitive tests. The models predicted the scores of 7/10 tests (median correlation coefficient, 0.47; range, 0.39–0.57) from 0.6% to 5.4% of the matrix entries; 84% of the predictive edges were between nodes of different networks. Critically involved cortical regions (≥10 adjacent edges) included predominantly left-sided nodes of the visual, somatomotor, dorsal/ventral attention, and default mode networks. Highly critical nodes (≥15 edges) included the default mode network’s left temporal and bilateral posterior cingulate cortex.
Conclusions
These results suggest that the cognitive performance of pretreated glioma patients is strongly related to structural connectivity between multiple brain networks and depends on the integrity of known network hubs also involved in other neurological disorders.
Graphical Abstract
Graphical Abstract
Fakes and forgeries are objects of fascination. This volume contains a series of thirteen articles devoted to fakes and forgeries of written artefacts from the beginnings of writing in Mesopotamia to ...modern China. The studies emphasise the subtle distinctions conveyed by an established vocabulary relating to the reproduction of ancient artefacts and production of artefacts claiming to be ancient: from copies, replicas and imitations to fakes and forgeries. Fakes are often a response to a demand from the public or scholarly milieu, or even both. The motives behind their production may be economic, political, religious or personal – aspiring to fame or simply playing a joke. Fakes may be revealed by combining the study of their contents, codicological, epigraphic and palaeographic analyses, and scientific investigations. However, certain famous unsolved cases still continue to defy technology today, no matter how advanced it is. Nowadays, one can find fakes in museums and private collections alike they abound on the antique market, mixed with real artefacts that have often been looted. The scientific community’s attitude to such objects calls for ethical reflection.
PDF
