Combining amino acid PET and MRI imaging increases accuracy to define malignant areas in adult glioma.

Accurate determination of the extent and grade of adult-type diffuse gliomas is critical to patient management. In clinical practice, contrast-enhancing areas of diffuse gliomas in magnetic resonance imaging (MRI) sequences are usually used to target biopsy, surgery, and radiation therapy, but there can be discrepancies between these areas and the actual tumor extent. Here we show that adding 18F-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) to MRI sequences accurately locates the most malignant areas of contrast-enhancing gliomas, potentially impacting subsequent management and outcomes. We present a prospective analysis of over 300 serial biopsy specimens from 23 patients with contrast-enhancing adult-type diffuse gliomas using a hybrid PET-MRI scanner to compare T2-weighted and contrast-enhancing MRI images with FET-PET. In all cases, we observe and confirm high FET uptake in early PET acquisitions (5-15 min after 18F-FET administration) outside areas of contrast enhancement on MRI, indicative of high-grade glioma. In 30% cases, inclusion of FET-positive sites changes the biopsy result to a higher tumor grade.

Functional State and Rehabilitation of Patients after Primary Brain Tumor Surgery for Malignant and Nonmalignant Tumors: A Prospective Observational Study.

The aim of this study was to compare the pre- and postoperative function of patients qualifying for resection of malignant and nonmalignant primary brain tumors to determine the relationship among tumor type, function, and the course of rehabilitation after surgery. This single-center, prospective, observational study recruited 92 patients requiring prolonged postoperative rehabilitation during their inpatient stay, who were divided into a nonmalignant tumor group (n = 66) and a malignant tumor group (n = 26). Functional status and gait efficiency were assessed using a battery of instruments. Motor skills, postoperative complications, and length of hospital stay (LoS) were recorded and compared between groups. The frequency and severity of postoperative complications, the time needed to attain individual motor skills, and the proportion of patients losing independent gait (~30%) were similar between groups. However, paralysis and paresis were more frequent in the malignant tumor group before surgery (p < 0.001). While nonmalignant tumor patients deteriorated more according to all scales after surgery, patients with malignant tumors were still characterized by worse ADL, independence, and performance at discharge. Worse functional outcomes in the malignant tumor group did not affect LoS or rehabilitation. Patients with malignant and nonmalignant tumors have similar rehabilitation needs, and patient expectation-especially those with nonmalignant tumors-should be appropriately managed.

Uncovering the molecular landscape of meningiomas and the impact of perioperative steroids on patient survival.

BACKGROUND: The current literature on meningioma reveals a gap in knowledge regarding the impact of genetic factors on patient survival. Furthermore, there is a lack of data on the relationship between the perioperative use of corticosteroids and patient survival in meningioma patients. Our study aims to overcome these gaps by investigating the correlation between genetic factors and overall survival and the effect of postoperative corticosteroids and other clinical characteristics on patient outcomes in meningioma patients. METHODS: A retrospective analysis of the medical records of 85 newly diagnosed meningioma patients treated from 2016 to 2017 with follow-up until December 2022 was performed. RESULTS: NF2 mutations occurred in 60% of tumors, AKT1 mutations in 8.2%, and TRAF7 mutations in 3.6%. Most tumors in the parasagittal region had the NF2 mutation. On the other hand, almost all tumors in the sphenoid ridge area did not have the NF2 mutation. AKT-1-mutated meningiomas had more frequent peritumoral edema. Patients who received steroids perioperatively had worse overall survival (OS) than those without steroids (p = 0.034). Moreover, preoperative peri-meningioma edema also was associated with worse OS (p < 0.003). Contrarily, NF2 mutations did not influence survival. CONCLUSIONS: The combination of clinical, pathomorphological, and genetic data allows us to characterize the tumor better and assess its prognosis. Corticosteroids perioperatively and peri-meningioma edema were associated with shorter OS, according to our study. Glucocorticoids should be used judiciously for the shortest time required to achieve symptomatic relief.

Rehabilitation Outcomes for Patients with Motor Deficits after Initial and Repeat Brain Tumor Surgery.

Repeat surgery is often required to treat brain tumor recurrences. Here, we compared the functional state and rehabilitation of patients undergoing initial and repeat surgery for brain tumors to establish their individual risks that might impact management. In total, 835 patients underwent operations, and 139 (16.6%) required rehabilitation during the inpatient stay. The Karnofsky performance status, Barthel index, and the modified Rankin scale were used to assess functional status, and the gait index was used to assess gait efficiency. Motor skills, postoperative complications, and length of hospital stay were recorded. Patients were classified into two groups: first surgery (n = 103) and repeat surgery (n = 30). Eighteen percent of patients required reoperations, and these patients required prolonged postoperative rehabilitation as often as those operated on for the first time. Rehabilitation was more often complicated in the repeat surgery group (p = 0.047), and the complications were more severe and persistent. Reoperated patients had significantly worse motor function and independence in activities of daily living before surgery and at discharge, but the deterioration after surgery affected patients in the first surgery group to a greater extent according to all metrics (p < 0.001). The length of hospital stay was similar in both groups. These results will be useful for tailoring postoperative rehabilitation during a hospital stay on the neurosurgical ward as well as planning discharge requirements after leaving the hospital.

MGMT Promoter Methylation as a Prognostic Factor in Primary Glioblastoma: A Single-Institution Observational Study.

Glioblastoma is the most malignant central nervous system tumor, which represents 50% of all glial tumors. The understanding of glioma genesis, prognostic evaluation, and treatment planning has been significantly enhanced by the discovery of molecular genetic biomarkers. This study aimed to evaluate survival in patients with primary glioblastoma concerning O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and other clinical factors. The study included 41 newly diagnosed glioblastoma patients treated from 2011 to 2014 in the 10th Military Research Hospital and Polyclinic, Poland. All patients underwent surgical resection followed by radiation and chemotherapy with alkylating agents. The MGMT promoter methylation was evaluated in all patients, and 43% were found to be methylated. In 26 and 15 cases, gross total resection and subtotal resection were conducted, respectively. Patients with a methylated MGMT promoter had a median survival of 504 days, while those without methylation had a median survival of 329 days. The group that was examined had a median age of 53. In a patient group younger than 53 years, those with methylation had significantly longer overall survival (639 days), compared to 433.5 days for patients without methylation. The most prolonged survival (551 days) was in patients with MGMT promoter methylation after gross total resection. The value of MGMT promoter methylation as a predictive biomarker is widely acknowledged. However, its prognostic significance remains unclear. Our findings proved that MGMT promoter methylation is also an essential positive prognostic biomarker.

Quality of Life after Surgical Treatment of Brain Tumors.

Quality of life is one of the parameters that characterize the success of brain tumor treatments, along with overall survival and a disease-free life. Thus, the main aim of this research was to evaluate the quality of life after the surgical treatment of brain tumors. The research material included 236 patients who were to undergo surgery for brain tumors. The participants completed the quality of life questionnaires EORTC QLQ-C30 (version 3.0) and EORTC QLQ-BN20 on the day of admission to the department, on the fifth day after the removal of the brain tumor, and thirty days after the surgical procedure. Descriptive statistics, Student's t-test, the Kruskal-Wallis test, the Shapiro-Wolf test, ANOVA, and Fisher's least significant difference post hoc test were performed. The mean score of the questionnaire before the surgical procedure amounted to 0.706, 5 days after surgery it amounted to 0.614, and 30 days after surgery to 0.707. The greatest reduction in the quality of life immediately after the procedure was observed in patients with low-grade glial tumors (WHO I, II) and extracerebral tumors (meningiomas and neuromas). Thirty days after surgery, an improvement in the quality of life was observed in all included groups. The greatest improvement was recorded in the group of patients operated on for meningioma and neuroblastoma, and the lowest in patients treated for metastatic tumors. Contemporary surgical procedures used in neurosurgery reduce the quality of life in patients with brain tumors only in the early postoperative period. Histopathological diagnoses of these tumors impact the quality of life of patients.

Survival after reoperation for recurrent glioblastoma multiforme: A prospective study.

PURPOSE: Glioblastoma multiforme (GBM) is the most common malignant brain tumor. Moreover, GBM recurs in nearly all patients. Although a standard STUPP protocol has been widely used for newly diagnosed GBM, no standard regimen has been established for recurrent patients. Here we evaluated the clinical value of recurrent GBM reoperation by comparing overall survival and quality of life (QoL) in patients with recurrent GBM undergoing repeat surgery or conservative treatment. METHODS: This was a prospective study of 165 patients with GBM receiving first operations for their disease between 2011 and 2013 at two tertiary neurosurgery centers in Poland. Thirty-five eligible patients were re-operated for recurrence (the study group), and 35 patients were selected as the control group using propensity score matching. A model was created to determine advantageous prognostic factors for longer survival of patients qualifying for reoperation using stepwise linear regression. RESULTS: The mean overall survival of patients undergoing repeat surgery was 528 days compared to 297 days in patients who did not undergo repeat surgery. Reoperation did not result in a significant deterioration in performance status as measured by the Karnofsky Performance Scale. Older age, the presence of symptoms of increased intracranial pressure, and a shorter period between initial operation and reoperation were independent predictors of a worse outcome. CONCLUSION: In selected patients, reoperation for recurrent GBM prolongs survival with no significant deteriorations in performance status.

Coated Blade Spray-Mass Spectrometry as a New Approach for the Rapid Characterization of Brain Tumors.

Brain tumors are neoplasms with one of the highest mortality rates. Therefore, the availability of methods that allow for the quick and effective diagnosis of brain tumors and selection of appropriate treatments is of critical importance for patient outcomes. In this study, coated blade spray-mass spectrometry (CBS-MS), which combines the features of microextraction and fast ionization methods, was applied for the analysis of brain tumors. In this approach, a sword-shaped probe is coated with a sorptive material to enable the extraction of analytes from biological samples. The analytes are then desorbed using only a few microliters of solvent, followed by the insertion of the CBS device into the interface on the mass spectrometer source. The results of this proof-of-concept experiment confirmed that CBS coupled to high-resolution mass spectrometry (HRMS) enables the rapid differentiation of two histologically different lesions: meningiomas and gliomas. Moreover, quantitative CBS-HRMS/MS analysis of carnitine, the endogenous compound, previously identified as a discriminating metabolite, showed good reproducibility with the variation below 10% when using a standard addition calibration strategy and deuterated internal standards for correction. The resultant data show that the proposed CBS-MS technique can be useful for on-site qualitative and quantitative assessments of brain tumor metabolite profiles.

Investigating the Potential Use of Chemical Biopsy Devices to Characterize Brain Tumor Lipidomes.

The development of a fast and accurate intraoperative method that enables the differentiation and stratification of cancerous lesions is still a challenging problem in laboratory medicine. Therefore, it is important to find and optimize a simple and effective analytical method of enabling the selection of distinctive metabolites. This study aims to assess the usefulness of solid-phase microextraction (SPME) probes as a sampling method for the lipidomic analysis of brain tumors. To this end, SPME was applied to sample brain tumors immediately after excision, followed by lipidomic analysis via liquid chromatography-high resolution mass spectrometry (LC-HRMS). The results showed that long fibers were a good option for extracting analytes from an entire lesion to obtain an average lipidomic profile. Moreover, significant differences between tumors of different histological origin were observed. In-depth investigation of the glioma samples revealed that malignancy grade and isocitrate dehydrogenase (IDH) mutation status impact the lipidomic composition of the tumor, whereas 1p/19q co-deletion did not appear to alter the lipid profile. This first on-site lipidomic analysis of intact tumors proved that chemical biopsy with SPME is a promising tool for the simple and fast extraction of lipid markers in neurooncology.

Comparison of the Functional State and Motor Skills of Patients after Cerebral Hemisphere, Ventricular System, and Cerebellopontine Angle Tumor Surgery.

Brain tumor location is an important factor determining the functional state after brain tumor surgery. We assessed the functional state and course of rehabilitation of patients undergoing surgery for brain tumors and assessed the location-dependent risk of loss of basic motor skills and the time needed for improvement after surgery. There were 835 patients who underwent operations, and 139 (16.6%) required rehabilitation during the inpatient stay. Karnofsky Performance Scale, Barthel Index, and the modified Rankin scale were used to assess functional status, whereas Gait Index was used to assess gait efficiency. Motor skills, overall length of stay (LOS) in hospital, and LOS after surgery were recorded. Patients were classified into four groups: cerebral hemisphere (CH), ventricular system (VS), and cerebellopontine angle (CPA) tumors; and a control group not requiring rehabilitation. VS tumor patients had the lowest scores in all domains compared with the other groups before surgery (p < 0.001). Their performance further deteriorated after surgery and by the day of discharge. They most often required long-lasting postoperative rehabilitation and had the longest LOS (35 days). Operation was most often required for CH tumors (77.7%), and all metrics and LOS parameters were better in these patients (p < 0.001). Patients with CPA tumors had the best outcomes (p < 0.001). Most patients (83.4%) with brain tumors did not require specialized rehabilitation, and LOS after surgery in the control group was on average 5.1 days after surgery. VS tumor patients represent a rehabilitation challenge. Postoperative rehabilitation planning must take the tumor site and preoperative condition into account.

Metabolomic Phenotyping of Gliomas: What Can We Get with Simplified Protocol for Intact Tissue Analysis?

Glioblastoma multiforme is one of the most malignant neoplasms among humans in their third and fourth decades of life, which is evidenced by short patient survival times and rapid tumor-cell proliferation after radiation and chemotherapy. At present, the diagnosis of gliomas and decisions related to therapeutic strategies are based on genetic testing and histological analysis of the tumor, with molecular biomarkers still being sought to complement the diagnostic panel. This work aims to enable the metabolomic characterization of cancer tissue and the discovery of potential biomarkers via high-resolution mass spectrometry coupled to liquid chromatography and a solvent-free sampling protocol that uses a microprobe to extract metabolites directly from intact tumors. The metabolomic analyses were performed independently from genetic and histological testing and at a later time. Despite the small cohort analyzed in this study, the results indicated that the proposed method is able to identify metabolites associated with different malignancy grades of glioma, as well as IDH and 1p19q codeletion mutations. A comparison of the constellation of identified metabolites and the results of standard tests indicated the validity of using the characterization of one comprehensive tumor phenotype as a reflection of all diagnostically meaningful information. Due to its simplicity, the proposed analytical approach was verified as being compatible with a surgical environment and applicable for large-scale studies.

Dural sinus thrombosis after resection of vestibular schwannoma using suboccipital retrosigmoid approach-thrombosis classification and management proposal.

Dural sinus thrombosis is one of the complications after posterior fossa surgery. However, that topic is not described well with regard to vestibular schwannoma surgery using the unique suboccipital retrosigmoid approach. We analyzed retrospectively medical records and radiological investigations of 116 patients. The including criteria were histopathologically confirmed vestibular schwannoma operated on using the retrosigmoid approach, preoperative and postoperative contrast-enhanced MRI, and at least 1-year follow-up. The patient group included 36% males and 64% females. The average age was 47.3 ± 13.9 years. Sixty percent of the tumors were classified as T4b according to the Hannover scale and their mean volume was 13.73 ± 10.28 cm3. There were no signs of thrombosis preoperatively. Postoperative changes in the dural sinuses were found in 26 (22%) cases. In 7 (27%) cases, there was an external compression by the hemostatic agent, and in 19 (73%) cases, a thrombus was visualized in the sinus lumen. The size of the sinus, age, and the tumor size were not risk factors for thrombosis, whereas an intraoperative sinus injury was a statistically significant risk factor (p = 0.0012). All of the patients diagnosed with thrombosis were in good clinical condition in long-term follow-up, except one fatal case. Complete recanalization was observed in 58% of cases after 1-year follow-up. Postoperative changes in the dural venous sinuses are a frequent finding after vestibular schwannoma surgery using the suboccipital retrosigmoid approach. Intraoperative dural injury is a risk factor for thrombosis. Thrombosis in that group of patients is usually asymptomatic and does not influence the prognosis.

Infratentorial Stereotactic Biopsy of Brainstem and Cerebellar Lesions.

Stereotactic biopsy of posterior fossa lesions is often regarded as hazardous due to the critical structures in that area. Therefore, the aim of the study was to evaluate the diagnostic accuracy and safety of infratentorial stereotactic biopsy of brainstem or cerebellar lesions and its associations with other clinical, laboratory, and radiological parameters. From January 2000 to May 2021, 190 infratentorial stereotactic biopsies of posterior fossa tumors, including 108 biopsies of brainstem lesions, were performed. Moreover, 63 supratentorial biopsies of cerebral peduncle lesions were analyzed to compare the safety and efficacy of both approaches. Additionally, the presence of antibodies against Toxoplasma gondii and Epstein-Barr Virus (EBV) were documented in 67 and 66 patients, respectively, and magnetic resonance imaging (MRI) scans were evaluated in 114 patients. Only 4% of patients had minor complications and 1.5% had major complications, including one patient who died from intracranial bleeding. Nine (4.7%) biopsies were non-diagnostic. Isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed in 29 patients, and were non-diagnostic in only 3 (10.3%) cases. Patients with high-grade gliomas (HGG) were more frequently seropositive for T. gondii than individuals with low-grade gliomas (LGG; p < 0.001). A total of 27% of HGG and 41% of LGG were non-enhancing on MRI. The infratentorial approach is generally safe and reliable for biopsy of brainstem and cerebellar lesions. In our study, the safety and efficacy of supratentorial biopsy of the cerebral peduncle and infratentorial biopsy of lesions below the cerebral peduncle were comparably high. Moreover, patients with HGG were more frequently seropositive for T. gondii than patients with LGG, and the relationship between toxoplasmosis and gliomagenesis requires further investigation.

New chemical biopsy tool for spatially resolved profiling of human brain tissue in vivo.

It is extremely challenging to perform chemical analyses of the brain, particularly in humans, due to the restricted access to this organ. Imaging techniques are the primary approach used in clinical practice, but they only provide limited information about brain chemistry. Solid-phase microextraction (SPME) has been presented recently as a chemical biopsy tool for the study of animal brains. The current work demonstrates for the first time the use of SPME for the spatially resolved sampling of the human brain in vivo. Specially designed multi-probe sampling device was used to simultaneously extract metabolites from the white and grey matter of patients undergoing brain tumor biopsies. Samples were collected by inserting the probes along the planned trajectory of the biopsy needle prior to the procedure, which was followed by metabolomic and lipidomic analyses. The results revealed that studied brain structures were predominantly composed of lipids, while the concentration and diversity of detected metabolites was higher in white than in grey matter. Although the small number of participants in this research precluded conclusions of a biological nature, the results highlight the advantages of the proposed SPME approach, as well as disadvantages that should be addressed in future studies.

Profiling of Carnitine Shuttle System Intermediates in Gliomas Using Solid-Phase Microextraction (SPME).

Alterations in the carnitine shuttle system may be an indication of the presence of cancer. As such, in-depth analyses of this pathway in different malignant tumors could be important for the detection and treatment of this disease. The current study aims to assess the profiles of carnitine and acylcarnitines in gliomas with respect to their grade, the presence of isocitrate dehydrogenase (IDH) mutations, and 1p/19q co-deletion. Brain tumors obtained from 19 patients were sampled on-site using solid-phase microextraction (SPME) immediately following excision. Analytes were desorbed and then analyzed via liquid chromatography-high-resolution mass spectrometry. The results showed that SPME enabled the extraction of carnitine and 22 acylcarnitines. An analysis of the correlation factor revealed the presence of two separate clusters: short-chain and long-chain carnitine esters. Slightly higher carnitine and acylcarnitine concentrations were observed in the higher-malignancy tumor samples (high vs. low grade) and in those samples with worse projected clinical outcomes (without vs. with IDH mutation; without vs. with 1p/19q co-deletion). Thus, the proposed chemical biopsy approach offers a simple solution for on-site sampling that enables sample preservation, thus supporting comprehensive multi-method analyses.

Treating Aggression and Self-destructive Behaviors by Stimulating the Nucleus Accumbens: A Case Series.

Self-destructive and aggressive behaviors can have a significant impact on the quality of life of affected individuals and their carrers. While deep brain stimulation (DBS) has been applied to the treatment of self-destructive and aggressive behaviors in isolated cases, clinical data on this treatment modality are still lacking. We therefore assessed responses to treatment with bilateral DBS of the nucleus accumbens in six patients with severe self-destructive and aggressive behaviors. Three patients had Tourette syndrome and three had other underlying predispositions including obsessive compulsive disorder, cerebral palsy, encephalitis, and epilepsy. Patients were followed up for between 2 and 7 years, and patients were assessed using the Modified Overt Aggression Scale (six patients) and the Buss-Perry Aggression Questionnaire (three patients able to complete the questionnaire on their own). DBS reduced self-destructive and aggressive behaviors by 30-100% and by an average of 74.5%. Patients with Tourette syndrome responded better to DBS and improved by 27.3% according to the Buss-Perry Aggression Questionnaire. These results suggest that nuclei accumbens stimulation may be an effective treatment for aggressive and self-destructive behaviors regardless of etiology.

Morphological Analysis of Cerebral Artery Fenestrations and Their Correlation with Intracranial Aneurysms.

BACKGROUND: Fenestrations of cerebral arteries are congenital variants that develop when primitive vessels fuse incompletely. An association between the incidence of aneurysm and a fenestrated artery has been noted in the radiological literature. However, technical limitations of radiological studies may hamper visualization of small fenestrations and aneurysms. We sought to analyze a large, postmortem collection of human brains to assess the association between aneurysm formation and the presence of fenestrations. METHODS: This study included 333 formalin-fixed brains. The arachnoid was dissected under a microscope, the cerebral arteries were completely exposed, and fenestrations and aneurysms were identified and measured. For each specimen, age, sex, and all vascular abnormalities and variations were recorded for analysis. RESULTS: Fenestrations were present in 41% of the specimens, and 37% of these were multiple. Fenestrations were 3.1 ± 2.5 mm long and most commonly occurred in the anterior communicating artery (63%). Aneurysms were present in 8% of the specimens, usually in the anterior communicating artery or the middle cerebral artery. An aneurysm correlated with a fenestration was detected in 2% of all specimens (n = 4) and was not statistically significant (P = 0.18). CONCLUSIONS: Fenestrations of the intracranial arteries are a common anatomical finding. They are present most often in the anterior communicating artery. Most aneurysms were detected in the anterior communicating artery and middle cerebral artery. We conclude that the existence of an aneurysm in a fenestrated artery is an incidental, rather than causal, relationship.

Influence of Epilepsy on the Quality of Life of Patients with Brain Tumors.

Epilepsy is a common consequence of brain tumors, occurring in 35 to 75% of cases. Here we evaluated the influence of epilepsy on the quality of life (QoL) of patients with malignant brain tumors (primary and metastatic) and assessed which areas of function are most affected by epilepsy and brain tumors. Sixty patients undergoing brain tumor surgery at the Neurosurgery Clinic of the 10th Military Research Hospital, Bydgoszcz, Poland (30 with epilepsy and 30 without epilepsy) were studied. Relationships between categorical variables were determined with Pearson's chi-squared test, while continuous data were analyzed with the Mann-Whitney U-test. A p value < 0.05 was considered statistically significant. A multiple regression model was used for multivariate analysis of QoL. Patients with epilepsy more frequently reported memory disorders as a problem in their daily life. There were trends towards greater impairments in social, professional, and family life, sports and recreational activities, and daily physical activities in brain tumor patients with epilepsy rather than those without epilepsy. Higher frequency and generalized seizures significantly and adversely influenced the ability of patients to leave home and drive vehicles, but a proportion of patients with frequent, generalized seizures continued to drive regardless. Patients with generalized seizures considered the adverse effects of taking medicines as significantly disruptive. Memory disorders significantly affect the QoL of patients with epilepsy, and the importance of stopping driving must be emphasized by all healthcare professionals.

Glioma Biopsy Based on Hybrid Dual Time-Point FET-PET/MRI-A Proof of Concept Study.

Neuroimaging based on O-[2-(18F)fluoroethyl]-l-tyrosine (FET)-PET provides additional information on tumor grade and extent compared with MRI. Dynamic PET for biopsy target selection further improves results but is often clinically impractical. Static FET-PET performed at two time-points may be a good compromise, but data on this approach are limited. The aim of this study was to compare the histology of lesions obtained from two challenging glioma patients with targets selected based on hybrid dual time-point FET-PET/MRI. Five neuronavigated tumor biopsies were performed in two difficult cases of suspected glioma. Lesions with (T1-CE) and without contrast enhancement (T1 and T2-FLAIR) on MRI were selected. Dual time-point FET-PET imaging was performed 5-15 min (PET10) and 45-60 min (PET60) after radionuclide injection. The most informative FET-PET/MRI images were coregistered with MRI in time of biopsy planning. Five biopsy targets (three from high uptake and two from moderate uptake FET areas) thought to represent the most malignant sites and tumor extent were selected. Histopathological findings were compared with FET-PET and MRI images. Increased FET uptake in the area of non-CE locations on MRI correlated well with high-grade gliomas localized as far as 3 cm from T1-CE foci. Selecting a target in the motor cortex based on FET kinetics defined by dual time-point PET resulted in a grade IV diagnosis after previous negative biopsies based on MRI. An additional grade III diagnosis was obtained from an area of glioma infiltration with moderate FET uptake (between 1 and 1.25 SUV). These findings seem to show that dual time-point FET-PET-based biopsies can provide additional and clinically useful information for glioma diagnosis. Selection of targets based on dual time-point images may be useful for determining the most malignant tumor areas and may therefore be useful for resection and radiotherapy planning.