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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-[18F]fluoroethyl)-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.

Purpose Following multimodality therapy, glioma patients may suffer from reduced health-related quality of life (QoL). 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 QoL. Methods In 121 patients with pretreated gliomas of WHO CNS grades 3 or 4, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET, resting-state functional MRI (rs-fMRI) and self-reported QoL 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, affection of white matter tracts and rs-fMRI network nodes by different types of lesions, and within rs-fMRI functional connectivity on QoL were analyzed. Results Gliomas of the right hemisphere were associated with significantly less favorable outcomes in physical, role, emotional and social functioning, compared to left-sided tumors. Most QoL scores correlated significantly with the affection of right-sided white-matter tracts by T2/FLAIR hyperintensities and with the loss of within-network functional connectivity of right-sided functional nodes. Tumors of the left hemisphere caused significantly more communication deficits. Conclusion In pretreated high-grade gliomas, right hemisphere rather than left hemisphere lesions are associated with decreased quality of life in most domains, except communication ability. These impairments are associated mainly with T2/FLAIR lesions affecting white matter tracts and functional nodal connectivity in the right hemisphere. The data suggest that sparing the right hemisphere from treatment-related tissue damage may improve quality of life in glioma patients.

The goal of this study was to compare the value of contrast-enhanced MRI and O-(2-[

Purpose Integrated histomolecular diagnostics of gliomas according to the World Health Organization (WHO) classification of 2016 has refined diagnostic accuracy and prediction of prognosis. This study aimed at exploring the prognostic value of dynamic O-(2-[18F]-fluoroethyl)-l-tyrosine (FET) PET in newly diagnosed, histomolecularly classified astrocytic gliomas of WHO grades III or IV. Methods Before initiation of treatment, dynamic FET PET imaging was performed in patients with newly diagnosed glioblastoma (GBM) and anaplastic astrocytoma (AA). Static FET PET parameters such as maximum and mean tumour/brain ratios (TBRmax/mean), the metabolic tumour volume (MTV) as well as the dynamic FET PET parameters time-to-peak (TTP) and slope, were obtained. The predictive ability of FET PET parameters was evaluated concerning the progression-free and overall survival (PFS, OS). Using ROC analyses, threshold values for FET PET parameters were obtained. Subsequently, univariate Kaplan-Meier and multivariate Cox regression survival analyses were performed to assess the predictive power of these parameters for survival. Results Sixty patients (45 GBM and 15 AA patients) of two university centres were retrospectively identified. Patients with isocitrate dehydrogenase (IDH)-mutant or O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated tumours had a significantly longer PFS and OS (both P 25 min (AUC, 0.90; sensitivity, 90%; specificity, 87%; P

Amino acid positron emission tomography (PET) using O-(2-[A 61-year-old patient with glioblastoma initially underwent partial tumor resection and died 11 weeks after completion of chemoradiation with concurrent temozolomide. Three days before the patient died, a follow-up FET PET and MRI scan indicated tumor progression. Autopsy was performed 48 hours after death. After formalin fixation, a 7-cm bihemispherical segment of the brain containing the entire tumor mass was cut into 3500 consecutive 20μm coronal sections. Representative sections were stained with hematoxylin and eosin stain, cresyl violet, and glial fibrillary acidic protein immunohistochemistry. An experienced neuropathologist identified areas of dense and diffuse neoplastic infiltration, astrogliosis, and necrosis. In vivo FET PET, MRI datasets, and postmortem histology were co-registered and compared by 3 experienced physicians.Increased uptake of FET in the area of equivocal contrast enhancement on MRI correlated very well with dense infiltration by vital tumor cells and showed tracer kinetics typical for malignant gliomas. An area of predominantly reactive astrogliosis showed only moderate uptake of FET and tracer kinetics usually observed in benign lesions.This case report impressively documents the correct imaging of a progressive glioblastoma by FET PET.

O-(2-[[SUVDexamethasone treatment appears to increase the [

To compare the diagnostic performance of O-(2-Thirty-two pretreated gliomas (25 progressive or recurrent tumors, 7 treatment-related changes) were investigated withThis pilot study suggests that

The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2-Ninety patients with newly diagnosed and untreated gliomas with a static and dynamicSixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBRData suggest that static and dynamic

Both perfusion-weighted MR imaging (PWI) and O-(2-Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated withThe diagnostic accuracy ofBoth

We investigated the potential of textural feature analysis of O-(2-[Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamicDiagnostic accuracy increased from 81 % for TBRTextural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic• Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

Proline and hydroxyproline represent major constituents of mammalian structural proteins, especially of collagen. An efficient radiosynthesis of the (18)F-labeled proline derivatives cis-/trans-4-[(18)F]fluoro-L-proline was developed two decades ago with the aim to investigate various diseases with altered collagen synthesis using Positron-Emission- Tomography (PET). A number of studies have explored cis-4-[(18)F]fluoro-L-proline uptake in various pathologies associated with increased collagen formation and in neoplastic lesions, but so far the results have not been very promising. Trans-4-[(18)F]fluoro-L-proline has not yet been investigated in detail, however the compound exhibits considerable differences in metabolic behavior and biodistribution compared with its cis-enantiomer. In recent years, the D-isomers of cis- /trans-4-[(18)F]fluoro-proline have been considered as PET tracers as well, and it was observed that both exhibit a preferred uptake into the brain compared with their L-isomers. Surprisingly, a high uptake of cis-4-[(18)F]fluoro-D-proline was found in brain areas exhibiting secondary neurodegeneration as well as in areas of radionecrosis after treatment of brain tumors. In this article, the present knowledge on the biological and physiological properties of cis-/trans-4-[(18)F]fluoro-D/L-proline and the results in various pathologies are reviewed, including some previously unpublished results from our laboratory.

Monitoring of radiochemotherapy (RCX) in patients with glioblastoma is difficult because unspecific alterations in magnetic resonance imaging with contrast enhancement can mimic tumor progression. Changes in tumor to brain ratios (TBRs) in positron emission tomography (PET) using O-(2-¹⁸fluoroethyl)-l-tyrosine (¹⁸F-FET) after RCX with temozolomide of patients with glioblastoma have been shown to be valuable parameters to predict survival. The kinetic behavior of ¹⁸F-FET in the tumors is another promising parameter to analyze tumor metabolism. In this study, we investigated the predictive value of dynamic ¹⁸F-FET PET during RCX of glioblastoma. Time-activity curves (TACs) of ¹⁸F-FET uptake of 25 patients with glioblastoma were evaluated after surgery (FET-1), early (7-10 days) after completion of RCX (FET-2), and 6 to 8 weeks later (FET-3). Changes in the time to peak (TTP) and the slope of the TAC (10-50 minutes postinjection) were analyzed and related to survival. Changes in kinetic parameters of ¹⁸F-FET uptake after RCX showed no relationship with survival time. In contrast, the high predictive value of changes of TBR to predict survival was confirmed. We conclude that dynamic ¹⁸F-FET PET does not provide additional prognostic information during RCX. Static ¹⁸F-FET PET imaging (20-40 minutes postinjection) appears to be sufficient for this purpose and reduces costs.

After cerebral ischemia or trauma, secondary neurodegeneration may occur in brain regions remote from the lesion. Little is known about the capacity of cerebral gliomas to induce secondary neurodegeneration. A previous study showed that cis-4-[(18)F]fluoro-D-proline (D-cis-[(18)F]FPro) detects secondary reactions of thalamic nuclei after cortical infarction with high sensitivity. Here we investigated the potential of D-cis-[(18)F]FPro to detect neuronal reactions in remote brain areas in the F98 rat glioma model using ex vivo autoradiography. Although the tumor tissue of F98 gliomas showed no significant D-cis-[(18)F]FPro uptake, we observed prominent tracer uptake in 7 of 10 animals in the nuclei of the ipsilateral thalamus, which varied with the specific connectivity with the cortical areas affected by the tumor. In addition, strong D-cis-[(18)F]FPro accumulation was noted in the hippocampal area CA1 in two animals with ipsilateral F98 gliomas involving hippocampal subarea CA3 rostral to that area. Furthermore, focal D-cis-[(18)F]FPro uptake was present in the necrotic center of the tumors. Cis-4-[(18)F]fluoro-D-proline uptake was accompanied by microglial activation in the thalamus, in the hippocampus, and in the necrotic center of the tumors. The data suggest that brain tumors induce secondary neuronal reactions in remote brain areas, which may be detected by positron emission tomography (PET) using D-cis-[(18)F]FPro.

Estimating tissue water content using high field MRI, such as 3 Tesla (T), is challenging due to the difficulty in dissociating the radio frequency inhomogeneity pattern from the signal arising from tissue intrinsic proton density (PD) variations. To overcome this problem the longitudinal relaxation time T1 can be combined with an initial guess of the PD to yield the desired PD bias correction. However, it is necessary to know whether T1 effects, i.e., any effect contributing to T1 while being independent of tissue hydration, influence the estimated correction.Twenty-five healthy subjects underwent a quantitative 3T MRI protocol enabling acquisition of 64 slices with 1 mm in-plane resolution and 2 mm slice thickness in 14 min. Influence of T1 effects on the estimated water content map is evaluated using a dedicated method including T1 and T2 * information and region of interest-based water content values are compared with the literature.Our analysis indicates that the PD bias correction based on T1 is largely insensitive to T1 effects. Besides, water content results are in good agreement with literature values obtained at 1.5T.This study demonstrates the applicability of a PD bias correction based on T1 to yield tissue water content at 3T.