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A phosphorylated tau epitope specific for paired helical filaments in Alzheimer's disease is recognized by monoclonal antibody PHF-1. Healthy adult brains lack the PHF-1 epitope (PHF-1 tau), but it is transiently expressed by immature neurons during development. We have found that proliferating SH-SY5Y human neuroblastoma cells also express PHF-1 tau. Consistent with the recent finding that cell-cycle-dependent kinases can phosphorylate tau in vitro, flow cytometry showed that mitotic SH-SY5Y cells were up to 18-fold more PHF-1 immunoreactive than nonmitotic cells. On immunoblots, PHF-1 tau in mitotic and nonmitotic cells also was strikingly different. First, mitosis induced a prominent PHF-1 reactive band at 120 kDa, which likely accounted for the large increase in PHF-1 signal seen at mitosis. Although the size of the 120-kDa band is consistent with it being the high-molecular-weight form of tau, other antibodies to tau did not recognize it. Second, mitosis caused a hyperphosphorylation of the PHF-1 immunoreactive tau band normally seen at 50 kDa. In mitotic cells this band had an increased intensity and molecular weight. Alkaline phosphatase treatment abolished tau M(r) heterogeneity, verifying that the variations in mobility were due to phosphorylation. These data show that cell-cycle-dependent hyperphosphorylation of tau occurs in intact cells, and they support the hypothesis that aberrant activity of cell-cycle-dependent kinases may contribute to tau phosphorylation and PHF formation in Alzheimer's disease.

Background: Bevacizumab (BEV), at a standard dose of 10 mg/kg every 2 weeks is associated with prolonged progression-free survival (PFS) but no improvement in overall survival (OS) in recurrent glioblastoma (rGBM). Few studies have examined the potential dose-dependent efficacy of BEV. In Ontario, reimbursement for the costs of BEV varies, and as a result, our practice began to routinely use lower dose regimens. The main aim of this study was to ensure that there was no harm to patients who received the low dose protocol., Methods: A single-center retrospective study of patients given BEV for rGBM between 2015 and 2020 was performed. Clinical and treatment data including BEV dose regimen [SD (10 mg/kg every 2 weeks) vs. LD (5 mg/kg every 2-3 weeks or 10 mg/kg every 3 weeks)] received at the time of rGBM diagnosis were captured. Overall survival (OS) and progression-free survival (PFS) on BEV were compared using the Kaplan-Meier product-limit method. Log-rank test was used to compare potential predictive factors. Cox regression model was performed for multivariable analysis of OS and PFS., Results: A total of 96 patients were included with a median follow-up duration of 6.84 months (range 1.12-50.63 months) from the date of the first infusion. The LD group consisted of 55 of the 96 patients. By virtue of funding mechanisms for BEV, the median age in the LD group was significantly higher (62 vs. 54 years p = 0.009). There was no difference in MGMT status between the two groups (p = 0.60). The LD group had prolonged median PFS (5.89 months versus 3.22 months; p = 0.0112) and OS (10.23 months versus 6.28 months; p = 0.0010). Multivariable analysis including the dose of BEV, the extent of resection, gender, and age revealed that standard dose of BEV, subtotal resection, and female sex were associated with worse overall survival. Nine patients in the SD group vs. 18 patients in the LD group reported an adverse event related to BEV., Conclusion: For patients with recurrent GBM, we found that a low dose regimen of BEV was associated with prolonged OS and PFS compared to the standard dose regimen. Lower dose schedules may be a better and more cost-effective option for patients with rGBM. Lower costs might provide more equitable access to this very important palliative drug., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neuritogenesis and synapse formation are transient phenomena mediated in part by filopodial attachments (Tsui, Lankford, and Klein, Proc. Natl. Acad. Sci. 82:8256-8260 1985). The attachments can be labeled by antisera against adherons, adhesive microparticles isolated from cell culture media (Tsui, Schubert, and Klein, J. Cell Biol. 106:2095-2108 1988). Here, two monoclonal antibodies raised against adherons have been found to recognize transiently expressed membrane antigens of developing avian retina. Early in development, monoclonal antibody (mAb) AD1 stained antigens that spanned the entire tissue. With time, immunoreactivity became restricted to optic fiber, ganglion cell, and inner plexiform layers. Immunoblots of embryonic day (E) 13 retina showed a broad band at 66-72 kD for particulate fractions and a fine band at 70 kD for soluble fractions. The particulate forms disappeared as retinas matured, but the soluble form did not. mAb AD2 initially labeled retina antigens of optic fiber, ganglion cell, and inner plexiform layers (IPL). Labeling in the plexiform layer showed discrete lamina. Immunoreactivity first appeared at E9, peaked at E15, and then disappeared shortly after hatching. In isolated cells, AD2 labeled small cell surface aggregates. Cytoarchitectural studies, using whole-mount transmission electron microscopy, showed AD2 antigen in cell surface microfilaments, including some that joined filopodia together. The adheron antigens recognized by mAbs AD1 and AD2 thus were (1) topographically restricted; (2) associated with cell surfaces; and (3) developmentally down-regulated. This pattern suggests a role in developmentally transient cell surface phenomena, such as neurite extension or junction biogenesis.

Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616–0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS (P <.001). Conclusion: WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: Brain tumors are common, requiring physicians to have a precise understanding of them for accurate diagnosis and treatment. Considering that various histological tumor types present different cellularity, we conducted this research to examine the role of apparent diffusion coefficient (ADC) values in the differential diagnosis and pathologic grading of brain tumor types. Methods: In this cross‐sectional study, we gathered pathology reports of histological samples of adult brain tumors. The tissue sample of brain tumors were examined histologically by a pathologist. The magnetic resonance imaging data of these patients were interpreted by a neuroradiologist. The measured ADC values and ADC ratios were calculated. Standard mean ADC values were expressed as 10−6 mm2/s. The findings were compared according to the histological diagnosis of each tumor. Results: Sixty‐eight patients were included in the study: 34 (50%) were male, and 34 (50%) were female. The average age of the patients was 51.69 + 16.40 years. In the examination of tumor type, 16 (23.5%) were astrocytoma, 9 (13.2%) were oligodendroglioma, 20 (29.4%) were glioblastoma, 4 (5.9%) were medulloblastoma, and 19 (27.9%) were metastatic tumors. the average value of ADC was statistically significantly different according to the pathological type of tumor (p < 0.001). The two‐by‐two comparison of average ADC among tumor types revealed significant differences, except for oligodendroglioma and glioblastoma (p‐value = 0.87) and glioblastoma and medulloblastoma (p‐value = 0.347). The average value of ADC and ADC ratio was statistically significantly different according to the pathological grade of the tumor (p < 0.001). In the two‐by‐two comparison of average ADC between all pathological grades of the tumor showed a significance difference except for Grade I and Grade II (p‐value = 0.355). The mean value of ADC and ADC ratio for glioblastoma and metastatic tumors showed no significant difference. Conclusion: The assessment of brain tumor grade through ADC examination will help to estimate prognosis and devising suitable therapeutic strategies. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging is increasingly available for brain investigation. Image interpretation of intracranial space-occupying lesions often includes the derived apparent diffusion coefficient (ADC) analysis. In human medicine, ADC can help discriminate between benign and malignant lesions in intracranial tumors. This study investigates the difference in ADC values depending on the sample strategies of image analysis. MRI examination, including diffusionweighted images of canine and feline patients presented between 2015 and 2020, were reviewed retrospectively. Patients with single, large intracranial space-occupying lesions were included. Lesions homogeneity was subjectively scored. ADC values were calculated using six different methods of sampling (M1-M6) on the ADC map. M1 included as much as possible of the lesion on a maximum of five consecutive slices; M2 included five central and five peripheral ROIs; M3 included a single ROI on the solid part of the lesion; M4 included three central ROIs on one slice; M5 included three central ROIs on different slices; and M6 included one large ROI on the entire lesion. A total of 201 animals of various breeds, genders, and ages were analyzed. ADC values differed significantly between M5 against M2 (peripheral) (p < 0.001), M5 against M6 (p = 0.009), and M4 against M2 (peripheral) (p = 0.005). When lesions scored as homogeneous in all sequences were excluded, an additional significant difference in three further sampling methods was present (p < 0.005). ADC of single, large, intracranial space-occupying lesions differed significantly in half of the tested methods of sampling. Excluding homogeneous lesions, additional significant differences among the sampling methods were present. The obtained results should increase awareness of the variability of the ADC, depending on the sample strategies used. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging is increasingly available for brain investigation. Image interpretation of intracranial space-occupying lesions often includes the derived apparent diffusion coefficient (ADC) analysis. In human medicine, ADC can help discriminate between benign and malignant lesions in intracranial tumors. This study investigates the difference in ADC values depending on the sample strategies of image analysis. MRI examination, including diffusionweighted images of canine and feline patients presented between 2015 and 2020, were reviewed retrospectively. Patients with single, large intracranial space-occupying lesions were included. Lesions homogeneity was subjectively scored. ADC values were calculated using six different methods of sampling (M1--M6) on the ADC map. M1 included as much as possible of the lesion on a maximum of five consecutive slices; M2 included five central and five peripheral ROIs; M3 included a single ROI on the solid part of the lesion; M4 included three central ROIs on one slice; M5 included three central ROIs on different slices; and M6 included one large ROI on the entire lesion. A total of 201 animals of various breeds, genders, and ages were analyzed. ADC values differed significantly between M5 against M2 (peripheral) (p < 0.001), M5 against M6 (p = 0.009), and M4 against M2 (peripheral) (p = 0.005). When lesions scored as homogeneous in all sequences were excluded, an additional significant difference in three further sampling methods was present (p < 0.005). ADC of single, large, intracranial space-occupying lesions differed significantly in half of the tested methods of sampling. Excluding homogeneous lesions, additional significant differences among the sampling methods were present. The obtained results should increase awareness of the variability of the ADC, depending on the sample strategies used. [ABSTRACT FROM AUTHOR]

Glioma is amalignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important member of the tumor microenvironment (TME), are widely distributed in circulation. Recently, the discovery of cranial-meningeal channels and intracranial lymphatic vessels has provided new insights into the origins of neutrophils in the CNS. Neutrophils in the brain may originate more from the skull and adjacent vertebral bone marrow. They cross the blood-brain barrier (BBB) under the action of chemokines and enter the brain parenchyma, subsequently migrating to the glioma TME and undergoing phenotypic changes upon contact with tumor cells. Under glycolytic metabolism model, neutrophils show complex and dual functions in different stages of cancer progression, including participation in the malignant progression, immune suppression, and anti-tumor effects of gliomas. Additionally, neutrophils in the TME interact with other immune cells, playing a crucial role in cancer immunotherapy. Targeting neutrophils may be a novel generation of immunotherapy and improve the efficacy of cancer treatments. This article reviews the molecular mechanisms of neutrophils infiltrating the central nervous system from the external environment, detailing the origin, functions, classifications, and targeted therapies of neutrophils in the context of glioma. [ABSTRACT FROM AUTHOR]

Background: The role of isocitrate dehydrogenase (IDH) mutation status for glioma stratification and prognosis is established. While structural magnetic resonance image (MRI) is a promising biomarker, it may not be sufficient for non-invasive characterisation of IDH mutation status. We investigated the diagnostic value of combined diffusion tensor imaging (DTI) and structural MRI enhanced by a deep radiomics approach based on convolutional neural networks (CNNs) and support vector machine (SVM), to determine the IDH mutation status in Central Nervous System World Health Organization (CNS WHO) grade 2–4 gliomas. Methods: This retrospective study analyzed the DTI-derived fractional anisotropy (FA) and mean diffusivity (MD) images and structural images including fluid attenuated inversion recovery (FLAIR), non-enhanced T1-, and T2-weighted images of 206 treatment-naïve gliomas, including 146 IDH mutant and 60 IDH-wildtype ones. The lesions were manually segmented by experienced neuroradiologists and the masks were applied to the FA and MD maps. Deep radiomics features were extracted from each subject by applying a pre-trained CNN and statistical description. An SVM classifier was applied to predict IDH status using imaging features in combination with demographic data. Results: We comparatively assessed the CNN-SVM classifier performance in predicting IDH mutation status using standalone and combined structural and DTI-based imaging features. Combined imaging features surpassed stand-alone modalities for the prediction of IDH mutation status [area under the curve (AUC) = 0.846; sensitivity = 0.925; and specificity = 0.567]. Importantly, optimal model performance was noted following the addition of demographic data (patients' age) to structural and DTI imaging features [area under the curve (AUC) = 0.847; sensitivity = 0.911; and specificity = 0.617]. Conclusions: Imaging features derived from DTI-based FA and MD maps combined with structural MRI, have superior diagnostic value to that provided by standalone structural or DTI sequences. In combination with demographic information, this CNN-SVM model offers a further enhanced non-invasive prediction of IDH mutation status in gliomas. [ABSTRACT FROM AUTHOR]

Objective: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma. Methods: This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m2 of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ (150-200 mg/m2 × 5 d during each 28-d cycle) plus anlotinib (8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Results: Thirty-three patients received the planned treatment. The median PFS was 10.9 months (95% CI, 9.9-18.7 months) and the 12-month PFS rate was 48.5%. The median OS was 17.4 months (95% CI, 14.5-21.1 months) and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58% (n = 19)], hypoalbuminemia [46% (n = 15)], and hypercholesterolemia [46% (n = 15)] during concurrent chemoradiotherapy and leukopenia [73% (n = 24)], hypertriglyceridemia [67% (n = 22)], and neutropenia [52% (n = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1 (HR, 5.6; 95% CI, 1.3-23.7; P = 0.021) and RP1L1 alterations (HR, 11.1; 95% CI, 2.2-57.2; P = 0.004) were associated with a significantly shorter PFS. Conclusions: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of amide proton transfer-weighted (APTw) MRI imaging and its derived radiomics in classifying adult-type diffuse glioma. Materials and methods: In this prospective study, APTw imaging was performed on 129 patients with adult-type diffuse gliomas. The mean APTw-related metrics (chemical exchange saturation transfer ratio (CESTR), CESTR normalized with the reference value (CESTRnr), and relaxation-compensated inverse magnetization transfer ratio (MTRRex)) and radiomic features within 3D tumor masks were extracted. APTw-radiomics models were developed using a support vector machine (SVM) classifier. Sensitivity analysis with tumor area of interest, different histogram cutoff values, and other classifiers were conducted. Results: CESTR, CESTRnr, and MTRRex in glioblastomas were all significantly higher (p < 0.0003) than those of oligodendrogliomas and astrocytomas, with no significant difference between oligodendrogliomas and astrocytomas. The APTw-related metrics for IDH-wildtype and high-grade gliomas were significantly higher (p < 0.001) than those for the IDH-mutant and low-grade gliomas, with area under the curve (AUCs) of 0.88 for CESTR. The CESTR-radiomics models demonstrated accuracies of 84% (AUC 0.87), 83% (AUC 0.83), 90% (AUC 0.95), and 84% (AUC 0.86) in predicting the IDH mutation status, differentiating glioblastomas from astrocytomas, distinguishing glioblastomas from oligodendrogliomas, and determining high/low grade prediction, respectively, but showed poor performance in distinguishing oligodendrogliomas from astrocytomas (accuracy 63%, AUC 0.63). The sensitivity analysis affirmed the robustness of the APTw signal and APTw-derived radiomics prediction models. Conclusion: APTw imaging, along with its derived radiomics, presents a promising quantitative approach for prediction IDH mutation and grading adult-type diffuse glioma. Clinical relevance statement: Amide proton transfer-weighted imaging, a quantitative imaging biomarker, coupled with its derived radiomics, offers a promising non-invasive approach for predicting IDH mutation status and grading adult-type diffuse gliomas, thereby informing individualized clinical diagnostics and treatment strategies. Key Points: • This study evaluates the differences of different amide proton transfer-weighted metrics across three molecular subtypes and their efficacy in classifying adult-type diffuse glioma. • Chemical exchange saturation transfer ratio normalized with the reference value and relaxation-compensated inverse magnetization transfer ratio effectively predicts IDH mutation/grading, notably the first one. • Amide proton transfer-weighted imaging and its derived radiomics holds potential to be used as a diagnostic tool in routine clinical characterizing adult-type diffuse glioma. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a fatal brain tumour that is traditionally diagnosed based on histological features. Recent molecular profiling studies have reshaped the World Health Organization approach in the classification of central nervous system tumours to include more pathogenetic hallmarks. These studies have revealed that multiple oncogenic pathways are dysregulated, which contributes to the aggressiveness and resistance of GBM. Such findings have shed light on the molecular vulnerability of GBM and have shifted the disease management paradigm from chemotherapy to targeted therapies. Targeted drugs have been developed to inhibit oncogenic targets in GBM, including receptors involved in the angiogenic axis, the signal transducer and activator of transcription 3 (STAT3), the PI3K/AKT/mTOR signalling pathway, the ubiquitination-proteasome pathway, as well as IDH1/2 pathway. While certain targeted drugs showed promising results in vivo, the translatability of such preclinical achievements in GBM remains a barrier. We also discuss the recent developments and clinical assessments of targeted drugs, as well as the prospects of cell-based therapies and combinatorial therapy as novel ways to target GBM. Targeted treatments have demonstrated preclinical efficacy over chemotherapy as an alternative or adjuvant to the current standard of care for GBM, but their clinical efficacy remains hindered by challenges such as blood-brain barrier penetrance of the drugs. The development of combinatorial targeted therapies is expected to improve therapeutic efficacy and overcome drug resistance. [ABSTRACT FROM AUTHOR]

Objectives: Our study aims to determine the incidence and potential risk factors for cerebral radiation necrosis (CRN) following treatment of sinonasal malignancies. Methods: One hundred thirty‐two patients diagnosed with sinonasal malignancies over an 18‐year period were identified at two institutions. Forty‐six patients meeting inclusion criteria and treated with radiation therapy were included for analysis. Demographic and clinical‐pathologic characteristics were collected and reviewed. Post‐treatment magnetic resonance imaging (MRI) at least 1 year following treatment was reviewed to determine presence or absence of CRN. Results: CRN was identified on MRI in 8 of 46 patients (17.4%) following radiation treatment. Patients with a history of reirradiation were more likely to develop CRN (50% vs. 10.5%, p <.05). The BEDs of radiation were also higher in CRN patients compared to non‐CRN patients, but this difference was not significant (p >.05). CRN patients had a higher proportion of tumors with skull base involvement than non‐CRN patients (100% vs. 57.9%, p =.037). Demographics, comorbidities, pathology, primary tumor subsite, chemotherapy use, and stage of disease demonstrated no significant increase in risk of CRN. Conclusions: Reirradiation and tumor skull base involvement were significant risk factors associated with CRN. Higher average total prescribed and BEDs of radiation were seen in the CRN groups, but these differences were not statistically significant. Gender, comorbidities, tumor subsite, tumor location, and treatment type were not significantly different between groups. Level of evidence: Level 3. [ABSTRACT FROM AUTHOR]

Objectives: Differentiation between high-grade glioma (HGG) and post-treatment-related effects (PTRE) is challenging, but advanced imaging techniques were shown to provide benefit. We aim to investigate microstructure characteristics of metabolic compartments identified from amino acid PET and to evaluate the diagnostic potential of this multimodal and integrative O-(2-18F-fluoroethyl)-l-tyrosine-(FET)-PET and fast diffusion kurtosis imaging (DKI) approach for the detection of recurrence and IDH genotyping. Methods: Fifty-nine participants with neuropathologically confirmed recurrent HGG (n = 39) or PTRE (n = 20) were investigated using static 18F-FET PET and a fast-DKI variant. PET and advanced diffusion metrics of metabolically defined (80–100% and 60–75% areas of 18F-FET uptake) compartments were assessed. Comparative analysis was performed using Mann–Whitney U tests with Holm-Šídák multiple-comparison test and Wilcoxon signed-rank test. Receiver operating characteristic (ROC) curves, regression, and Spearman's correlation analysis were used for statistical evaluations. Results: Compared to PTRE, recurrent HGG presented increased 18F-FET uptake and diffusivity (MD60), but lower (relative) mean kurtosis tensor (rMKT60) and fractional anisotropy (FA60) (respectively p <.05). Diffusion metrics determined from the metabolic periphery showed improved diagnostic performance — most pronounced for FA60 (AUC = 0.86, p <.001), which presented similar benefit to 18F-FET PET (AUC = 0.86, p <.001) and was negatively correlated with amino acid uptake (rs = − 0.46, p <.001). When PET and DKI metrics were evaluated in a multimodal biparametric approach, TBRmax + FA60 showed highest diagnostic accuracy (AUC = 0.93, p <.001), which improved the detection of relapse compared to PET alone (difference in AUC = 0.069, p =.04). FA60 and MD60 distinguished the IDH genotype in the post-treatment setting. Conclusion: Detection of glioma recurrence benefits from a multimodal and integrative PET/DKI approach, which presented significant diagnostic advantage to the assessment based on PET alone. Clinical relevance statement: A multimodal and integrative 18F-FET PET/fast-DKI approach for the non-invasive microstructural characterization of metabolic compartments provided improved diagnostic capability for differentiation between recurrent glioma and post-treatment-related changes, suggesting a role for the diagnostic workup of patients in post-treatment settings. Key Points: • Multimodal PET/MRI with integrative analysis of 18F-FET PET and fast-DKI presents clinical benefit for the assessment of CNS cancer, particularly for the detection of recurrent high-grade glioma. • Microstructure markers of the metabolic periphery yielded biologically pertinent estimates characterising the tumour microenvironment, and, thereby, presented improved diagnostic accuracy with similar accuracy to amino acid PET. • Combined 18F-FET PET/fast-DKI achieved the best diagnostic performance for detection of high-grade glioma relapse with significant benefit to the assessment based on PET alone. [ABSTRACT FROM AUTHOR]

Purpose: Intraoperative magnetic resonance imaging (iMRI) has been efficacious in maximizing resection of high-grade gliomas (HGGs). In this single-institution study of patients with HGGs who underwent resection using iMRI, the authors present a volumetric-based survival analysis to evaluate progression-free survival (PFS) and overall survival (OS), as well as the impact of additional resection on survival., Methods: This retrospective analysis included patients with HGGs who underwent resection using iMRI from 2011 to 2021. Volumetric analyses of T1-weighted contrast-enhancing (T1W-CE), T2-weighted (T2W), and T2W fluid-attenuated inversion recovery (FLAIR) MRI sequences were assessed at preoperative, intraoperative, immediate postoperative, and three-month postoperative timepoints. Statistical analyses were carried out using log-rank and multivariable Cox proportional hazard regression analyses., Results: A total of 101 patients (median age 57.0 years) were treated. In keeping with prior studies, statistically significant associations between greater EOR and longer PFS and OS were seen (p = 0.012 and p = 0.006, respectively). The results demonstrated significant associations of lower preoperative T2W, 3-month postoperative T2W, and 3-month postoperative FLAIR volumes with longer PFS and OS (p = 0.045 and p = 0.026, p = 0.031 and p = 0.006, p = 0.018 and p = 0.004, respectively), as well as associations between lower immediate postoperative T2W and immediate postoperative FLAIR volumes with longer OS (p = 0.002 and p = 0.02). There was no observed association in either PFS or OS for patients undergoing additional resection after initial iMRI scan (p = 0.387 and p = 0.592)., Conclusion: This study of 101 patients with new or recurrent HGGs shows three-month postoperative T2W and FLAIR imaging volumes were significant prognosticators with respect to PFS and OS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Gliomas are the most commonly occurring brain tumour in adults and there remains no cure for these tumours with treatment strategies being based on tumour grade. All treatment options aim to prolong survival, maintain quality of life and slow the inevitable progression from low-grade to high-grade. Despite imaging advancements, the only reliable method to grade a glioma is to perform a biopsy, and even this is fraught with errors associated with under grading. Positron emission tomography (PET) imaging with amino acid tracers such as [ 18 F]fluorodopa ( 18 F-FDOPA), [ 11 C]methionine ( 11 C-MET), [ 18 F]fluoroethyltyrosine ( 18 F-FET), and 18 F-FDOPA are being increasingly used in the diagnosis and management of gliomas., Methods: In this review we discuss the literature available on the ability of 18 F-FDOPA-PET to distinguish low- from high-grade in newly diagnosed gliomas., Results: In 2016 the Response Assessment in Neuro-Oncology (RANO) and European Association for Neuro-Oncology (EANO) published recommendations on the clinical use of PET imaging in gliomas. However, since these recommendations there have been a number of studies performed looking at whether 18 F-FDOPA-PET can identify areas of high-grade transformation before the typical radiological features of transformation such as contrast enhancement are visible on standard magnetic resonance imaging (MRI)., Conclusion: Larger studies are needed to validate 18 F-FDOPA-PET as a non-invasive marker of glioma grade and prediction of tumour molecular characteristics which could guide decisions surrounding surgical resection., (© 2022. The Author(s).)

Purpose: Pseudoprogression (PsP) remains an elusive and clinically important, yet ill-defined, phenomena that, generally, involves a period of early radiographic progression (enhancement) followed by a period of radiographic stability or regression. In the current study, we utilized data from the control arm of a phase III clinical trial in newly-diagnosed glioblastoma to explore imaging characteristics of "clinically-defined PsP", or early radiographic progression (PFS < 6 months from chemoradiation) followed by a long post-progression residual overall survival (ROS > 12 months)., Methods: One hundred sixty-nine patients with newly-diagnosed GBM from the control arm of the AVAglio trial (NCT00943826) who presented with early radiographic progressive disease (PD) (< 6 months) were included. Clinical characteristics, topographical patterns, and radiomic features were compared between newly-diagnosed GBM exhibiting early PD and early death (< 12-month ROS, "true PD") with those exhibiting early PD and a long residual survival (> 12-month ROS, "clinically-defined PsP")., Results: "Clinically-defined PsP" occurred to 38.5% of patients with early PD, and was more associated with MGMT methylation (P = 0.02), younger age (P = 0.003), better neurological performance (P = 0.01), and lower contrast-enhancing tumor volume (P = 0.002) at baseline. GBM showing "true PD" occurred more frequently in the right internal capsule, thalamus, lentiform nucleus, and temporal lobe than those with "clinical PsP". Radiomic analysis predicted "clinical PsP" with > 70% accuracy on the validation dataset., Conclusion: Patients with early PD that eventually exhibit "clinically-defined PsP" have distinct clinical, molecular, and MRI characteristics. This information may be useful for treating clinicians to better understand the potential risks and outcome in patients exhibiting early radiographic changes following chemoradiation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In recent years, the development of advanced magnetic resonance imaging (MRI) technology and machine learning (ML) have created new tools for evaluating treatment response and prognosis of patients with high-grade gliomas (HGG); however, patient prognosis has not improved significantly. This is mainly due to the heterogeneity between and within HGG tumors, resulting in standard treatment methods not benefitting all patients. Moreover, the survival of patients with HGG is not only related to tumor cells, but also to noncancer cells in the tumor microenvironment (TME). Therefore, during preoperative diagnosis and follow-up treatment of patients with HGG, noninvasive imaging markers are needed to characterize intratumoral heterogeneity, and then to evaluate treatment response and predict prognosis, timeously adjust treatment strategies, and achieve individualized diagnosis and treatment. In this review, we summarize the research progress of conventional MRI, advanced MRI technology, and ML in evaluation of treatment response and prognosis of patients with HGG. We further discuss the significance of the TME in the prognosis of HGG patients, associate imaging features with the TME, indirectly reflecting the heterogeneity within the tumor, and shifting treatment strategies from tumor cells alone to systemic therapy of the TME, which may be a major development direction in the future. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 4., (© 2022 International Society for Magnetic Resonance in Medicine.)

Purpose: The presence of necrosis or microvascular proliferation was previously the hallmark for glioblastoma (GBM) diagnosis. The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/-10 copy changes. We hypothesize that these tumors are early histological GBM and will eventually develop the classic histological features., Methods: Medical records from 65 consecutive patients diagnosed with molGBM at three tertiary-care centers from our institution were retrospectively reviewed from November 2017-October 2021. Only patients who underwent reoperation for tumor recurrence and whose tissue at initial diagnosis and recurrence was available were included in this study. The detailed clinical, histopathological, and radiographic scenarios are presented., Results: Five patients were included in our final cohort. Three (60%) patients underwent reoperation for recurrence in the primary site and 2 (40%) underwent reoperation for distal recurrence. Microvascular proliferation and pseudopalisading necrosis were absent at initial diagnosis but present at recurrence in 4 (80%) patients. Radiographically, all tumors showed contrast enhancement, however none of them showed the classic radiographic features of GBM at initial diagnosis., Conclusions: In this manuscript we present preliminary data for a hypothesis that molGBMs are early histological GBMs diagnosed early in their natural history of disease and will eventually develop necrosis and microvascular proliferation. Further correlative studies are needed in support of this hypothesis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Since the overall glioma mass and its subcomponents-enhancing region (malignant part of the tumor), non-enhancing (less aggressive tumor cells), necrotic core (dead cells), and edema (water deposition)-are complex and irregular structures, non-Euclidean geometric measures such as fractal dimension (FD or "fractality") and lacunarity are needed to quantify their structural complexity. Fractality measures the extent of structural irregularity, while lacunarity measures the spatial distribution or gaps. The complex geometric patterns of the glioma subcomponents may be closely associated with the grade and molecular landscape. Therefore, we measured FD and lacunarity in the glioma subcomponents and developed machine learning models to discriminate between tumor grades and isocitrate dehydrogenase (IDH) gene status. 3D fractal dimension (FD3D) and lacunarity (Lac3D) were measured for the enhancing, non-enhancing plus necrotic core, and edema-subcomponents using preoperative structural-MRI obtained from the The Cancer Genome Atlas (TCGA) and University of California San Francisco Preoperative Diffuse Glioma MRI (UCSF-PDGM) glioma cohorts. The FD3D and Lac3D measures of the tumor-subcomponents were then compared across glioma grades (HGGs: high-grade gliomas vs. LGGs: low-grade gliomas) and IDH status (mutant vs. wild type). Using these measures, machine learning platforms discriminative of glioma grade and IDH status were developed. Kaplan-Meier survival analysis was used to assess the prognostic significance of FD3D and Lac3D measurements. HGG exhibited significantly higher fractality and lower lacunarity in the enhancing subcomponent, along with lower fractality in the non-enhancing subcomponent compared to LGG. This suggests that a highly irregular and complex geometry in the enhancing-subcomponent is a characteristic feature of HGGs. A comparison of FD3D and Lac3D between IDH-wild type and IDH-mutant gliomas revealed that mutant gliomas had ~2.5-fold lower FD3D in the enhancing-subcomponent and higher FD3D with lower Lac3D in the non-enhancing subcomponent, indicating a less complex and smooth enhancing subcomponent, and a more continuous non-enhancing subcomponent as features of IDH-mutant gliomas. Supervised ML models using FD3D from both the enhancing and non-enhancing subcomponents together demonstrated high-sensitivity in discriminating glioma grades (~97.9%) and IDH status (~94.4%). A combined fractal estimation of the enhancing and non-enhancing subcomponents using MR images could serve as a non-invasive, precise, and quantitative measure for discriminating glioma grade and IDH status. The combination of 2-hydroxyglutarate-magnetic resonance spectroscopy (2HG-MRS) with FD3D and Lac3D quantification may be established as a robust imaging signature for glioma subtyping., (© 2024 John Wiley & Sons Ltd.)

Background: Early and accurate identification of the metastatic tumor types of brain metastasis (BM) is essential for appropriate treatment and management., Methods: A total of 450 patients were enrolled from two centers as a primary cohort who carry 764 BMs originated from non-small cell lung cancer (NSCLC, patient = 173, lesion = 187), small cell lung cancer (SCLC, patient = 84, lesion = 196), breast cancer (BC, patient = 119, lesion = 200), and gastrointestinal cancer (GIC, patient = 74, lesion = 181). A third center enrolled 28 patients who carry 67 BMs (NSCLC = 24, SCLC = 22, BC = 10, and GIC = 11) to form an external test cohort. All patients received contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) MRI scans at 3.0 T before treatment. Radiomics features were calculated from BM and brain-to-tumor interface (BTI) region in the MRI image and screened using least absolute shrinkage and selection operator (LASSO) to construct the radiomics signature (RS). Volume of peritumor edema (VPE) was calculated and combined with RS to create a joint model. Performance of the models was assessed by receiver operating characteristic (ROC)., Results: The BTI-based RS showed better performance compared to BM-based RS. The combined models integrating BTI features and VPE can improve identification performance in AUCs in the training (LC/NLC vs. SCLC/NSCLC vs. BC/GIC, 0.803 vs. 0.949 vs. 0.918), internal validation (LC/NLC vs. SCLC/NSCLC vs. BC/GIC, 0.717 vs. 0.854 vs. 0.840), and external test (LC/NLC vs. SCLC/NSCLC vs. BC/GIC, 0.744 vs. 0.839 vs. 0.800) cohorts., Conclusion: This study indicated that BTI-based radiomics features and VPE are associated with the metastatic tumor types of BM., Competing Interests: Declarations. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Ethical approval: This retrospective study was approved by the Institutional Review Board of the Cancer Hospital of China Medical University, Shengjing Hospital of China Medical University, and the People's Hospital of Liaoning Province, and the consents from patients were waived., (© 2024. Italian Society of Medical Radiology.)

Background and Objectives: Photodynamic therapy (PDT) with talaporfin sodium is an intraoperative local therapy administered after the surgical removal of malignant gliomas. However, its clinical efficacy in a large patient population has not been determined. To analyze the clinical outcomes and prognosis in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients treated with PDT., Methods: This retrospective study included patients with newly diagnosed IDH-wildtype glioblastoma treated at Kobe University Hospital between January 2013 and December 2022. PDT involves irradiation of the resection cavity with a 664-nm semiconductor laser after an intravenous infusion of talaporfin sodium. The main outcome measures were the recurrence patterns and survival times, which were compared between the PDT and non-PDT groups. Univariate and multivariate analyses were used to determine the prognostic factors. In addition, adverse events and prognostic factors in the PDT group were analyzed., Results: A total of 44 and 56 patients were included in the PDT and non-PDT groups, respectively. The local recurrence rate was significantly lower in the PDT group than in the non-PDT group (51.3% vs 83.9%), whereas the distant recurrence and dissemination rates were significantly higher in the PDT group than in the non-PDT group (48.7% vs 16.1%). Two grade 3 adverse events were observed in the PDT group. The median progression-free survival and overall survival times were significantly longer in the PDT group than in the non-PDT group (progression-free survival: 10.8 vs 9.3 months, respectively, and overall survival: 24.6 vs 17.6 months, respectively). Multivariate analysis of the PDT groups revealed that younger age was an independent prognostic factor., Conclusion: PDT with talaporfin sodium provided effective local control with minimal adverse effects. The survival time of the patients treated with PDT was significantly longer than that of the patients who did not receive PDT. Therefore, a randomized controlled clinical trial on PDT is warranted., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Stereotactic MR-guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low-field MR-Linac faces substantial challenges due to dramatically lower signal-to-noise ratio (SNR) characteristics. While quantitative MRI and T 1 mapping of hypoxia biomarkers show promise, T 1 -to-noise ratio (T 1 NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen-enhanced (OE)-MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T 1 -weighted contrast images with simultaneous T 1 mapping., Purpose: To optimize MP2RAGE for low-field T 1 mapping; conduct experimental validation in a ground-truth phantom; establish feasibility and reproducibility of low-field MP2RAGE acquisition and T 1 mapping in healthy volunteers., Methods: The MP2RAGE optimization was performed to maximize the contrast-to-noise ratio (CNR) of T 1 values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low-field MP2RAGE images were acquired on a 0.35T MR-Linac (ViewRay MRIdian) using a multi-channel head coil. Validation of T 1 mapping was performed with a ground-truth Eurospin phantom, containing inserts of known T 1 values (400-850 ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T 1 maps. Mean (± SD) T 1 relative error, T 1 NR, and intersession coefficient of variation (CV) were determined. Whole-brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T 1 maps were generated. Mean (± SD) T 1 values for WM and GM were determined. Whole-brain T 1 histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel-by-voxel T 1 difference maps were generated to evaluate 3D spatial variation., Results: Low-field MP2RAGE optimization resulted in parameters: MP2RAGE TR of 3250 ms, inversion times (TI 1 /TI 2 ) of 500/1200 ms, and flip angles (α 1 /α 2 ) of 7/5°. Eurospin T 1 maps exhibited a mean (± SD) relative error of 3.45% ± 1.30%, T 1 NR of 20.13 ± 5.31, and CV of 2.22% ± 0.67% across all inserts. Whole-brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (± SD) T 1 values: 435.36 ± 10.01 ms for WM and 623.29 ± 14.64 ms for GM across subjects, showing excellent concordance with literature. Whole-brain T 1 histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel-level WM and GM T 1 values. Reproducibility analysis revealed a CV of 0.46% ± 0.31% and 0.35% ± 0.18% for WM and GM, respectively. Voxel-by-voxel T 1 difference maps show a normal 3D spatial distribution of noise in WM and GM., Conclusions: Low-field MP2RAGE proved effective in generating accurate, reliable, and reproducible T 1 maps with high T 1 NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE-MRI, this study establishes a foundation for TOLD T 1 mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR-guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging-to-treat cancers., (© 2024 American Association of Physicists in Medicine.)

The presence of a normal large blood vessel (LBV) in a tumor region can impact the evaluation of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and tumor classification. Hence, there is a need for automatic removal of LBVs from brain tissues including intratumoral regions for achieving an objective assessment of tumors. This retrospective study included 103 histopathologically confirmed brain tumor patients who underwent MRI, including DCE-MRI data acquisition. Quantitative DCE-MRI analysis was performed for computing various parameters such as wash-out slope (Slope-2), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), blood plasma volume fraction (V p ), and volume transfer constant (K trans ). An approach based on data-clustering algorithm, morphological operations, and quantitative DCE-MRI maps was proposed for the segmentation of normal LBVs in brain tissues, including the tumor region. Here, three widely used data-clustering algorithms were evaluated on two types of quantitative maps: (a) Slope-2, and (b) a new proposed combination of rCBV and Slope-2 maps. Fluid-attenuated inversion recovery-MRI hyperintense lesions were also automatically segmented using deep learning-based architecture. The accuracy of LBV segmentation was qualitatively assessed blindly by two experienced observers, and Likert scoring was also obtained from each individual and compared using Cohen's Kappa test, and multiple statistical features from quantitative DCE-MRI parameters were obtained in the segmented tumor. t-test and receiver operating characteristic (ROC) curve analysis were performed for comparing the effect of removal of LBVs on parameters as well as on tumor grading. k-means clustering exhibited better accuracy and computational efficiency. Tumors, in particular high-grade gliomas (HGGs), showed a high contrast compared with normal tissues (relative % difference = 18.5%) on quantitative maps after the removal of LBVs. Statistical features (95 th percentile values) of all parameters in the tumor region showed a statistically significant difference (p < 0.05) between with and without LBV maps. Similar results were obtained for the ROC curve analysis for differentiation between low-grade gliomas and HGGs. Moreover, after the removal of LBVs, the rCBV, rCBF, and V p maps show better visualization of tumor regions., (© 2024 John Wiley & Sons Ltd.)

Purpose: The Journal of Neuro-Oncology (JNO), established in 1983, plays a key role in publishing research on brain and spinal cord tumors. This study examines JNO's publication trends, focusing on country and gender representation to highlight its global impact., Methods: Statistical analyses were conducted using R. Gender of the first authors was predicted using a gender-guesser, and author affiliations were used to determine publication countries. We introduced a novel Country-Related Diversity (CRD) index to assess the JNO's representativeness, comparing a country's JNO publications to its overall neurosurgical output. An index value of 1 indicates proportional representation., Results: The JNO corpus, spanning from 1983 to 2024, comprises 8,154 documents with an average document age of 14.4 years. The average citation count per document is 28.71, with a rate of 2.16 citations per document per year. JNO's scientific output has grown significantly, peaking at 397 articles in 2011, with a long-term annual growth rate of 3.7%. The keyword analysis highlights "glioblastoma" as the most frequent term, reflecting the journal's neuro-oncological focus. Geographically, the U.S. led with 2,535 articles (40.1%), followed by China and Germany. International collaboration rose steadily, with multi-country publications increasing from 4.76% in 1983 to 20.98% in 2024. Analyzing contributions from different countries showed a converging CRD index toward 1 (P < 0.01), with U.S. and non-U.S. countries trending similarly. Upper-middle-income countries displayed fluctuating CRD patterns, whereas lower-middle-income countries lagged behind. Authorship analysis showed an increasing trend in co-authorship (P < 0.01), with the average number of authors per paper reaching 10.4 by 2024. Gender representation revealed a growing number of female first and senior authors, although males still dominate. By 2024, 32.9% of first authors and 21.6% of senior authors were female, signaling a gradual trend toward gender parity (P < 0.01)., Conclusions: The CRD index offers a standardized measure of country-specific research representation in the JNO. The convergence towards 1 reflects balanced international representation. JNO publication also reflects a trend toward gender equity, with a notable rise in female first authors, enhancing global research inclusivity., (© 2024. The Author(s).)

Purpose: Primary central nervous system (CNS) tumors are the second most common cancer in children and adolescents, leading to premature death and disability. Population-based survival estimates aid decision-making in cancer control, however data on survival for primary CNS tumors in Latin America is lacking. We describe survival rates for children with primary CNS tumors treated in ten Colombian cities. Methods: We analyzed data from children and adolescents newly diagnosed with cancer between 2012 and 2021, participating in the Childhood Cancer Clinical Outcomes Surveillance System (VIGICANCER) in ten cities in Colombia. VIGICANCER collects information on clinical outcomes from twenty-seven pediatric oncology units and conducts active follow-up every three months. VIGICANCER does not register craniopharyngiomas; we excluded intracranial germ cell tumors for this report. We used the Kaplan-Meier method to estimate the overall survival probability, stratified by sociodemographic variables, topography, WHO grading, receipt of radiation therapy, and type of surgical resection. We analyzed the prognostic capacity of variables using multivariate proportional Cox's regression, stratified by city and year of diagnosis. Results: During the study period, VIGICANCER included 989 primary CNS tumors in 879 children and 110 adolescents. The cohort median age was 9 years; 53% of patients were males, and 8% were Afro-descendants. Most common tumors were supratentorial astrocytomas (47%), astrocytic tumors (35%), medulloblastomas (20%), ependymomas (11%), and mixed and unspecified gliomas (10%). Five-year overall survival of the entire cohort was 54% (95% CI, 51-58); for supratentorial gliomas, WHO grade I was 77%, II was 62%, III-IV was 27%, respectively, and for medulloblastoma was 61%. The adjusted hazard rate ratio for patients with WHO grade III and IV, for those with subtotal resection, for brainstem location, and for those not receiving radiation therapy was 7.4 (95% CI, 4.7-11.8), 6.4 (95% CI, 4.2-9.8), 2.8 (95% 2.1-3.8), 2.0 (95% CI, 1.3-2.8) and 2.3 (95% CI, 1.7-3.0), respectively. Conclusion: We found that half of Colombia's children and adolescents with primary CNS tumors survive five years, compared to 70% to 80% in high-income countries. In addition to tumor biology and location, gross total resection was crucial for improved survival in this cohort. Systematic monitoring of survival and its determinants provides empirical data for guiding cancer control policies. [ABSTRACT FROM AUTHOR]

Background: Glioma is one of the most drug and radiation-resistant tumors. Gliomas suffer from inter- and intratumor heterogeneity which makes the outcome of similar treatment protocols vary from patient to patient. This article is aimed to overview the potential imaging markers for individual diagnosis, prognosis, and treatment response prediction in malignant glioma. Furthermore, the correlation between imaging findings and biological and clinical information of glioma patients is reviewed. Materials and Methods: The search strategy in this study is to select related studies from scientific websites such as PubMed, Scopus, Google Scholar, and Web of Science published until 2022. It comprised a combination of keywords such as Biomarkers, Diagnosis, Prognosis, Imaging techniques, and malignant glioma, according to Medical Subject Headings. Results: Some imaging parameters that are effective in glioma management include: ADC, FA, Ktrans, regional cerebral blood volume (rCBV), cerebral blood flow (CBF), ve, Cho/NAA and lactate/lipid ratios, intratumoral uptake of 18F-FET (for diagnostic application), RD, ADC, ve, vp, Ktrans, CBFT1, rCBV, tumor blood flow, Cho/ NAA, lactate/lipid, MI/Cho, uptakes of 18F-FET, 11C-MET, and 18F-FLT (for prognostic and predictive application). Cerebral blood volume and Ktrans are related to molecular markers such as vascular endothelial growth factor (VEGF). Preoperative ADCmin value of GBM tumors is associated with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. 2-hydroxyglutarate metabolite and dynamic 18F-FDOPA positron emission tomography uptake are related to isocitrate dehydrogenase (IDH) mutations. Conclusion: Parameters including ADC, RD, FA, rCBV, Ktrans, vp, and uptake of 18F-FET are useful for diagnosis, prognosis, and treatment response prediction in glioma. A significant correlation between molecular markers such as VEGF, MGMT, and IDH mutations with some diffusion and perfusion imaging parameters has been identified. [ABSTRACT FROM AUTHOR]

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Purpose: The aim of this study was to evaluate the image quality and feasibility of a field map-based technique to correct for susceptibility-induced geometric distortions which are typical for diffusion EPI brain imaging. Methods: We prospectively included 52 patients during clinical routine in this single-center study. All scans were performed on a 3T MRI. Patients' indications for MRI mainly consisted of suspected stroke due to the clinical presentation. For the morphological comparison of the corrected and uncorrected EPI diffusion, three experienced radiologists assessed the image quality of the sequences in a blinded and randomized fashion using a Likert scale (1 being poor; 5 being excellent). To ensure comparability of the two methods, an additional quantitative analysis of the apparent diffusion coefficient (ADC) was performed. Results: Corrected EPI diffusion was rated significantly superior in all the selected categories: overall level of artifacts (p < 0.001), degree of distortion at the frontal, temporal, occipital and brainstem levels (p < 0.001), conspicuousness of ischemic lesions (p < 0.001), image quality (p < 0.001), naturality (p < 0.001), contrast (p < 0.001), and diagnostic confidence (p < 0.001). Conclusion: Corrected EPI diffusion offers a significant reduction of geometric distortion in all evaluated brain regions and an improved conspicuousness of ischemic lesions. Image quality, overall artifacts, naturality, contrast and diagnostic confidence were also rated superior in comparison to uncorrected EPI diffusion. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the diagnostic value of imaging necrosis (Imnecrosis) in grading, predict the genotype and prognosis of gliomas, and further assess tumor necrosis by dynamic contrast-enhanced MR perfusion imaging (DCE-MRI). We retrospectively included 150 patients (104 males, mean age: 46 years old) pathologically proved as adult diffuse gliomas and all diagnosis was based on the 2021 WHO central nervous system (CNS) classification. The pathological necrosis (Panecrosis) and gene mutation information were collected. All patients underwent conventional and DCE-MRI examinations and had been followed until May 31, 2021. The Imnecrosis was determined by two experienced neuroradiologists. DCE-MRI derived metric maps have been post-processed, and the mean value of each metric in the tumor parenchyma, peritumoral and contralateral area were recorded. There was a strong degree of inter-observer agreement in defining Imnecrosis (Kappa = 0.668, p < 0.001) and a strong degree of agreement between Imnecrosis and Panecrosis (Kappa = 0.767, p < 0.001). Compared to low-grade gliomas, high-grade gliomas had more Imnecrosis (85.37%, p < 0.001), and Imnecrosis significantly increased with the grade of gliomas increasing. And Imnecrosis was significantly more identified in IDH-wildtype, 1p19q-non-codeletion, and CDKN2A/B-homozygous-deletion gliomas. Using multivariate Cox regression analysis, Imnecrosis was an independent and unfavorable prognosis factor (Hazard Ratio = 2.113, p = 0.046) in gliomas. Additionally, extravascular extracellular volume fraction (ve) in tumor parenchyma derived from DCE-MRI demonstrated the highest diagnostic efficiency in identifying Panecrosis and Imnecrosis with high specificity (83.3% and 91.9%, respectively). Imnecrosis can provide supplementary evidence beyond Panecrosis in grading, predicting the genotype and prognosis of gliomas, and ve in tumor parenchyma can help to predict tumor necrosis with high specificity. [ABSTRACT FROM AUTHOR]

Purpose: Glioma is a complex cancer comprising various subtypes and mutations, which may have different metabolic characteristics that can potentially be investigated and identified using perfusion imaging. Therefore, the aim of this work was to use radiomics and machine learning analysis of arterial spin labeling MRI data to automatically differentiate glioma subtypes and mutations., Methods: A total of 495 Arterial Spin Labeling (ASL) perfusion imaging datasets from the UCSF Glioma database were used in this study. These datasets were segmented to delineate the tumor volume and classified according to tumor grade, pathological diagnosis, and IDH status. Perfusion image data was obtained from a 3T MRI scanner using pseudo-continuous ASL. High level texture features were extracted for each ASL dataset using PyRadiomics after tumor volume segmentation and then analyzed using a machine learning framework consisting of ReliefF feature ranking and logistic model tree classification algorithms., Results: The results of the evaluation revealed balanced accuracies for the three endpoints ranging from 55.76% (SD = 4.28, 95% CI: 53.90-57.65) for the tumor grade using 25.4 ± 37.21 features, 62.53% (SD = 2.86, 95% CI: 61.27-63.78) for the mutation status with 23.3 ± 29.17 picked features, and 80.97% (SD = 1.83, 95% CI: 80.17-81.78) for the pathological diagnosis which used 47.3 ± 32.72 selected features., Conclusions: Radiomics and machine learning analysis of ASL perfusion data in glioma patients hold potential for aiding in the diagnosis and treatment of glioma, mainly for discerning glioblastoma from astrocytoma, while performance for tumor grading and mutation status appears limited., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Target population These recommendations apply to adult patients with recurrent WHO grade 2 infiltrative diffuse glioma (oligodendroglioma, astrocytoma).Questions and Recommendations:Imaging Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, do advanced imaging techniques using magnetic resonance spectroscopy, perfusion weighted imaging, diffusion weighted imaging or PET provide superior assessment of tumor recurrence and histologic progression compared to standard MRI neuroimaging?Recommendation Level III: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, advanced imaging techniques using magnetic resonance spectroscopy, perfusion weighted imaging, diffusion weighted imaging or PET are suggested for identification of tumor recurrence or histologic progression.Pathology Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, is molecular testing for IDH-1, IDH-2, and TP53 Mutations and MGMT promotor methylation mutation warranted for predicting survival and formulating treatment recommendations?Recommendation Level III: It is suggested that IDH mutation status be determined for diagnostic purposes. TP53 mutations occur early in WHO grade 2 diffuse glioma pathogenesis, remain stable, and are not suggested as a marker of predisposition to malignant transformation at recurrence or other measures of prognosis. Assessment of MGMT status is suggested as an adjunct to assessing prognosis. Assessment of CDK2NA status is suggested since this is associated with malignant progression of WHO grade 2 diffuse gliomas.Q2: In adult patients with suspected recurrence of histologically proven WHO Grade 2 diffuse glioma, is testing of proliferation indices (MIB-1 and/or BUdR) warranted for predicting survival and formulating treatment recommendations?Recommendation Level III: It is suggested that proliferative indices (MIB-1 or BUdR) be measured in WHO grade 2 diffuse glioma as higher proliferation indices are associated with increased likelihood of recurrence and shorter progression free and overall survival.Chemotherapy Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does addition of temozolomide (TMZ), other cytotoxic agents or targeted agents to their treatment regimen improve PFS and/or OS?Recommendation Level III: Temozolomide is suggested in the therapy of recurrent WHO grade 2 diffuse glioma as it may improve clinical symptoms. PCV is suggested in the therapy of WHO grade 2 diffuse glioma at recurrence as it may improve clinical symptoms with the strongest evidence being for oligodendrogliomas. TMZ is suggested as the initial choice for recurrent WHO grade 2 diffuse glioma. Carboplatin is not suggested as there is no significant benefit from carboplatin as single agent therapy for recurrent WHO grade 2 diffuse gliomas. There is insufficient evidence to make any recommendations regarding other agents in the management of recurrent WHO grade 2 diffuse glioma.Radiotherapy Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does addition of radiotherapy to treatment regimen improve PFS and/or OS?Recommendation Level III: Radiation is suggested at recurrence if there was no previous radiation treatment. Q2: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma after previous radiotherapy, does addition of re-irradiation or proton therapy to the treatment regimen improve PFS and/or OS?Recommendation Level III: It is suggested that re-irradiation be considered in the setting of WHO grade 2 diffuse glioma recurrence as it may provide benefit in PFS and OS.Surgery Q1: In adult patients with suspected recurrence of histologically proven WHO grade 2 diffuse glioma, does surgical resection improve PFS and/or OS?. There is insufficient evidence to make any new specific recommendations regarding the value of surgery or extent of resection in relationship to survival for recurrent WHO grade 2 diffuse glioma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Brain metastases commonly occur in patients with non-small cell lung cancer (NSCLC). Standard first-line treatment for NSCLC, without an EGFR, ALK or ROS1 mutation, is either chemoimmunotherapy or anti-PD-1 monotherapy. Traditionally, patients with symptomatic or untreated brain metastases were excluded from the pivotal clinical trials that established firstline treatment recommendations. The intracranial effectiveness of these treatment protocols has only recently been elucidated in small-scale prospective trials. Methods: Patients with NSCLC and brain metastases, treated with first-line chemoimmunotherapy or anti-PD-1 monotherapy were selected from the Australian Registry and biObank of thoracic cancers (AURORA) clinical database covering seven institutions. The primary outcome was a composite time-to-event (TTE) outcome, including extracranial and intracranial progression, death, or need for local intracranial therapy, which served as a surrogate for disease progression. The secondary outcome included overall survival (OS), intracranial objective response rate (iORR) and objective response rate (ORR). Results: 116 patients were included. 63% received combination chemoimmunotherapy and 37% received anti-PD-1 monotherapy. 69% of patients received upfront local therapy either with surgery, radiotherapy or both. The median TTE was 7.1 months (95% CI 5 - 9) with extracranial progression being the most common progression event. Neither type of systemic therapy or upfront local therapy were predictive of TTE in a multivariate analysis. The median OS was 17 months (95% CI 13-27). Treatment with chemoimmunotherapy was predictive of longer OS in multivariate analysis (HR 0.35; 95% CI 0.14 - 0.86; p=0.01). The iORR was 46.6%. The iORR was higher in patients treated with chemoimmunotherapy compared to immunotherapy (58% versus 31%, p=0.01). The use of chemoimmunotherapy being predictive of iORR in a multivariate analysis (OR 2.88; 95% CI 1.68 - 9.98; p=0.04). Conclusion: The results of this study of real-world data demonstrate the promising intracranial efficacy of chemoimmunotherapy in the first-line setting, potentially surpassing that of immunotherapy alone. No demonstrable difference in survival or TTE was seen between receipt of upfront local therapy. Prospective studies are required to assist clinical decision making regarding optimal sequencing of local and systemic therapies. [ABSTRACT FROM AUTHOR]

Accurate localization of gliomas, the most common malignant primary brain cancer, and its different sub-region from multimodal magnetic resonance imaging (MRI) volumes are highly important for interventional procedures. Recently, deep learning models have been applied widely to assist automatic lesion segmentation tasks for neurosurgical interventions. However, these models are often complex and represented as "black box" models which limit their applicability in clinical practice. This article introduces new hybrid vision Transformers and convolutional neural networks for accurate and robust glioma segmentation in Brain MRI scans. Our proposed method, TransXAI, provides surgeon-understandable heatmaps to make the neural networks transparent. TransXAI employs a post-hoc explanation technique that provides visual interpretation after the brain tumor localization is made without any network architecture modifications or accuracy tradeoffs. Our experimental findings showed that TransXAI achieves competitive performance in extracting both local and global contexts in addition to generating explainable saliency maps to help understand the prediction of the deep network. Further, visualization maps are obtained to realize the flow of information in the internal layers of the encoder-decoder network and understand the contribution of MRI modalities in the final prediction. The explainability process could provide medical professionals with additional information about the tumor segmentation results and therefore aid in understanding how the deep learning model is capable of processing MRI data successfully. Thus, it enables the physicians' trust in such deep learning systems towards applying them clinically. To facilitate TransXAI model development and results reproducibility, we will share the source code and the pre-trained models after acceptance at https://github.com/razeineldin/TransXAI. [ABSTRACT FROM AUTHOR]

Background: Arterial transit artifact (ATA) observed on arterial spin labeling (ASL) was recently suggested to be associated with improved functional outcomes following acute ischemic stroke (AIS). AIS is a heterogeneous disease with diverse pathogenic mechanisms depending on the stroke subtype. This study aimed to investigate the association between ATA and 3-month functional outcomes in AIS patients according to etiology subtypes. Methods: Consecutive patients with AIS were included. All patients underwent ASL MRI with postlabeling delay (PLD) of 1.5 and 2.5 s. ATA was assessed from the ASL images of both PLDs. Stroke etiologic subtypes were determined according to the modified TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Short-term functional outcomes were evaluated using the 3-month modified Rankin scale (mRS). Log-binomial regression was applied to analyze the association between ATA and functional outcomes at 3 months after stroke. Results: Ninety-eight AIS patients (62.73 ± 13.05 years; 68 men) were finally included. ATA was detected in forty-six patients and most frequently seen in the large-artery atherosclerosis (LAA) subtype (35/46). The ATA group exhibited a lower percentage of patients with mRS > 2 compared to the group without ATA (36.5% vs. 19.6%; P < 0.001). ATA was independently associated with better 3-month clinical outcomes (adjusted risk ratio, 0.35[95% CI, 0.16—0.74]) in the multivariate log-binomial regression model. After stratification by TOAST subtypes, a significant association was found between ATA and better outcomes in the LAA subtype (adjusted risk ratio, 0.20[ 95% CI, 0.05—0.72]) but not in cardioembolism and small artery occlusion (SVO) subtype. Conclusion: ATA is associated with better outcomes at 3 months in patients with AIS, especially in the LAA subtype, but this association attenuated in the cardioembolism and SVO subtypes. [ABSTRACT FROM AUTHOR]

Pediatric low-grade gliomas (pLGGs) are the most common brain tumor types affecting children. Although gross-total resection remains the treatment of choice, many tumors are not amenable to complete removal, because they either involve midline structures, such as the optic chiasm or hypothalamus, and are not conducive to aggressive resection, or have diffuse biological features and blend with the surrounding brain. Historically, radiation therapy was used as the second-line option for disease control, but with the recognition that this often led to adverse long-term sequelae, particularly in young children, conventional chemotherapy assumed a greater role in initial therapy for unresectable tumors. A variety of agents demonstrated activity, but long-term disease control was suboptimal, with more than 50% of tumors exhibiting disease progression within 5 years. More recently, it has been recognized that a high percentage of these tumors in children exhibit constitutive activation of the mitogen-activated protein kinase (MAPK) pathway because of BRAF translocations or mutations, NFI mutations, or a host of other anomalies that converged on MAPK. This led to phase 1, 2, and 3 trials that explored the activity of blocking this signaling pathway, and the efficacy of this approach compared to conventional chemotherapy. Despite initial promise of these strategies, not all children tolerate this therapy, and many tumors resume growth once MAPK inhibition is stopped, raising concern that long-term and potentially life-long treatment will be required to maintain tumor control, even among responders. This observation has led to interest in other treatments, such as immunotherapy, that may delay or avoid the need for additional treatments. This chapter will summarize the place of immunotherapy in the current armamentarium for these tumors and discuss prior results and future options to improve disease control, with a focus on our prior efforts and experience in this field., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Morphological imaging using MRI is essential for brain tumour diagnostics. Dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI), as well as amino acid PET, may provide additional information in ambiguous cases. Since PWI is often unavailable in patients referred for amino acid PET, we explored whether maps of relative cerebral blood volume (rCBV) in brain tumours can be extracted from the early phase of PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). Procedure: Using a hybrid brain PET/MRI scanner, PWI and dynamic 18F-FET PET were performed in 33 patients with cerebral glioma and four patients with highly vascularized meningioma. The time interval from 0 to 2 min p.i. was selected to best reflect the blood pool phase in 18F-FET PET. For each patient, maps of MR-rCBV, early 18F-FET PET (0–2 min p.i.) and late 18F-FET PET (20–40 min p.i.) were generated and coregistered. Volumes of interest were placed on the tumour (VOI-TU) and normal-appearing brain (VOI-REF). The correlation between tumour-to-brain ratios (TBR) of the different parameters was analysed. In addition, three independent observers evaluated MR-rCBV and early 18F-FET maps (18F-FET-rCBV) for concordance in signal intensity, tumour extent and intratumoural distribution. Results: TBRs calculated from MR-rCBV and 18F-FET-rCBV showed a significant correlation (r = 0.89, p < 0.001), while there was no correlation between late 18F-FET PET and MR-rCBV (r = 0.24, p = 0.16) and 18F-FET-rCBV (r = 0.27, p = 0.11). Visual rating yielded widely agreeing findings or only minor differences between MR-rCBV maps and 18F-FET-rCBV maps in 93 % of the tumours (range of three independent raters 91–94%, kappa among raters 0.78–1.0). Conclusion: Early 18F-FET maps (0–2 min p.i.) in gliomas provide similar information to MR-rCBV maps and may be helpful when PWI is not possible or available. Further studies in gliomas are needed to evaluate whether 18F-FET-rCBV provides the same clinical information as MR-rCBV. [ABSTRACT FROM AUTHOR]

Background: Gadolinium deposition in biological tissues was first reported in patients with renal failure. We aimed to investigate gadolinium deposition in the rat kidney after exposure to single and multiple doses of gadolinium and evaluate deposition for 1- and 3-month periods. We also aimed to determine any correlation between the amount of deposition and T1-weighted image intensity. Methods: Seventy rats (5 animals per group) were included in the sample, and 9 groups received a single dose (0.3, 0.6, and 1.2 mmol/kg) of gadolinium, and 1 group for each dose was sacrificed at the end of the first day, week, and month. Four groups received weekly doses (0.3 and 0.6 mmol/kg) and were sacrificed at the end of 6 and 12 weeks. Measurement of T1 intensities was carried out with postinjection images before sacrifice, and deposition was determined using inductively coupled plasma mass spectrometry. Results: The number of injections was associated with increased gadolinium deposition (P < .001) in the kidney. After the weekly injections, the deposited gadolinium levels did not significantly differ between the low and medium doses at the end of the sixth week (P = .067). There was no agreement between the observers regarding the measurement of T1 signal intensity in both single-dose and multidose experiments (P = .263 and P = .307, respectively). Conclusion: Deposition was dose dependent in the postinjection stage in contrast to the late stage in which deposition was not associated with dose or number of injections until the 12th week. T1 signal intensity measurement is unreliable for assessing deposition in the rat kidney. [ABSTRACT FROM AUTHOR]

Background: Although mutations in telomerase reverse transcriptase (TERT) promoter (TERTp) are the most common alterations in glioblastoma (GBM), predicting TERTp mutation status by preoperative imaging is difficult. We determined whether tumour-surrounding hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) were superior to those of contrast-enhanced lesions (CELs) in assessing TERTp mutation status using magnetic resonance imaging (MRI). Methods: This retrospective study included 114 consecutive patients with primary isocitrate dehydrogenase (IDH)- wild-type GBM. The apparent diffusion coefficient (ADC) and volume of CELs and FLAIR hyperintense lesions (FHLs) were determined, and the correlation between MRI features and TERTp mutation status was analyzed. In a subset of cases, FHLs were histopathologically analyzed to determine the correlation between tumor cell density and ADC. Results: TERTp mutations were present in 77 (67.5%) patients. The minimum ADC of FHLs was significantly lower in the TERTp-mutant group than in the TERTp-wild-type group (mean, 958.9 × 10-3 and 1092.1 × 10-3 mm2/s, respectively, P < 0.01). However, other MRI features, such as CEL and FHL volumes, minimum ADC of CELs, and FHL/CEL ratio, were not significantly different between the two groups. Histopathologic analysis indicated high tumor cell density in FHLs with low ADC. Conclusion: The ADC of FHLs was significantly lower in IDH-wild-type GBM with TERTp mutations, suggesting that determining the ADC of FHLs on preoperative MRI might be helpful in predicting TERTp mutation status and surgical planning. [ABSTRACT FROM AUTHOR]