Cerebral Glucose Metabolism in Patients with Chronic Disorders of Consciousness.

OBJECTIVE: To measure regional cerebral metabolic rate of glucose (CMRGlu) in patients with chronic disorders of consciousness (DOCs) using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: This retrospective cohort study examined 50 patients (mean age: 40.9 ± 20.1 years) with traumatic brain injury (TBI)-induced chronic DOCs [minimally conscious state (MCS)+, n = 20; MCS-, n = 15 and vegetative state (VS), n = 15]. We measured FDG-PET-based CMRGlu values in 12 regions of both brain hemispheres and compared those among MCS+, MCS - and VS patients. RESULTS: In both hemispheres, the regional CMRGlu reduced with consciousness deterioration in 11 of 12 regions (91.7%). In seven right hemisphere regions, CMRGlu values were markedly higher in MCS+ patients than in MCS- patients. Furthermore, CMRGlu was suggestively higher in the left occipital region in MCS- patients than in VS patients. CONCLUSION: Functional preservation in the left occipital region in patients with chronic DOCs might reflect an awareness of external environments, whereas extensive functional preservation in the right cerebral hemisphere might reflect communication motivation.

Spastic muscle stiffness evaluated using ultrasound elastography and evoked electromyogram in patients following severe traumatic brain injury: an observational study.

OBJECTIVE: To determine the relationship between muscle stiffness assessed using ultrasound shear wave elastography, spinal motor neuron excitability assessed using the F wave, and clinical findings of spasticity in patients with spastic muscle overactivity following severe traumatic brain injury. METHODS: This study enrolled 17 inpatients with severe traumatic brain injury and 20 healthy volunteers. Biceps brachii muscle stiffness was then evaluated using ultrasound shear wave speed. Spinal motor neuron excitability was evaluated using the F/M ratio recorded from abductor pollicis brevis muscle. Clinical parameters, such as the modified Ashworth scale and modified Tardieu scale, were assessed in the patient with traumatic brain injury. RESULTS: The patients with traumatic brain injury group had a significantly higher shear wave speed and F/M ratio compared with the healthy group. A higher shear wave speed was correlated with higher clinical spastic severity in patients with traumatic brain injury. The F/M ratio was not significantly correlated with clinical spastic severity. CONCLUSION: Ultrasound shear wave elastography might be helpful for assessing muscle stiffness in patients with spastic muscle overactivity following severe traumatic brain injury. Further studies comprising larger cohorts are warranted.

Characteristics of time-activity curves obtained from dynamic 11C-methionine PET in common primary brain tumors.

PURPOSE: The aim of this study was to assess whether dynamic PET with 11C-methionine (MET) (MET-PET) is useful in the diagnosis of brain tumors. METHODS: One hundred sixty patients with brain tumors (139 gliomas, 9 meningiomas, 4 hemangioblastomas and 8 primary central nervous system lymphomas [PCNSL]) underwent dynamic MET-PET with a 3-dimensional acquisition mode, and the maximum tumor MET-standardized uptake value (MET-SUV) was measured consecutively to construct a time-activity curve (TAC). Furthermore, receiver operating characteristic (ROC) curves were generated from the time-to-peak (TTP) and the slope of the curve in the late phase (SLOPE). RESULTS: The TAC patterns of MET-SUVs (MET-TACs) could be divided into four characteristic types when MET dynamics were analyzed by dividing the MET-TAC into three phases. MET-SUVs were significantly higher in early and late phases in glioblastoma compared to anaplastic astrocytoma, diffuse astrocytoma and the normal frontal cortex (P < 0.05). The SLOPE in the late phase was significantly lower in tumors that included an oligodendroglial component compared to astrocytic tumors (P < 0.001). When we set the cutoff of the SLOPE in the late phase to - 0.04 h-1 for the differentiation of tumors that included an oligodendroglial component from astrocytic tumors, the diagnostic accuracy was 74.2% sensitivity and 64.9% specificity. The area under the ROC curve was 0.731. CONCLUSIONS: The results of this study show that quantification of the MET-TAC for each brain tumor identified by a dynamic MET-PET study could be helpful in the non-invasive discrimination of brain tumor subtypes, in particular gliomas.

Fluorescein sodium-guided resection of intracranial lesions in 22 dogs.

OBJECTIVE: To evaluate the safety of an intraoperative fluorescein sodium (FS) injection and elucidate the relationships between the MRI findings, pathological diagnoses, and intraoperative staining characteristics of intracranial lesions in 22 dogs. STUDY DESIGN: Prospective case series. ANIMALS: Twenty-two dogs with intracranial lesions. METHODS: FS was intravenously administered to 22 dogs undergoing craniotomy for suspected intracranial tumors to evaluate perioperative and postoperative adverse effects. The intensities and patterns of gadolinium (Gd) enhancement on preoperative magnetic resonance imaging and intraoperative FS staining were graded, and their relationship was evaluated. Intraoperative FS staining characteristics and pathological diagnoses were compared. RESULTS: The only adverse effect noted was repetitive vomiting in 2 dogs. The intensities and patterns between preoperative Gd enhancement and intraoperative FS staining appeared to agree. High-grade glioma and histiocytic sarcoma had more intense FS staining. Lesions with strong Gd enhancement, including meningiomas and choroid plexus tumors, also had intense FS staining. CONCLUSION: The intraoperative use of FS is a simple and safe technique to guide the resection of intracranial lesions in dogs. The findings on Gd enhancement, FS staining, and histopathology appeared to agree but require validation in a larger set of cases. CLINICAL SIGNIFICANCE: The intraoperative use of FS may improve the prognosis of dogs with brain tumors by guiding the resection of lesions.

Current trends in mouse models of glioblastoma.

Glioblastoma is the most deadly brain tumor type and is characterized by a severe and high rate of angiogenesis, remaining an incurable disease in the majority of cases. Mechanistic understanding of glioblastoma initiation and progression is complicated by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell or tissue of origin. To determine these mechanisms, mouse models that recapitulate the molecular and histological characteristics of glioblastoma are required. Unlike in other malignancies, viral-mediated mouse models of glioblastoma rather than chemically induced mouse models have been developed because of its sensitivity to viruses. Based on recent molecular analyses reported for human glioblastoma, this review critically evaluates genetically engineered, xenograft, allograft, viral-mediated, and chemically induced mouse models of glioblastoma. Further, we focus on the clinical value of these models by examining their contributions to studies of glioblastoma prevention, tumorigenesis, and chemoresistance.

Pathological analysis of the surgical margins of resected glioblastomas excised using photodynamic visualization with both 5-aminolevulinic acid and fluorescein sodium.

During glioma resection, 5-aminolevulinic acid (5-ALA) and fluorescein sodium (Fl-Na) are used for photodynamic tumor visualization. The objective of this study was to evaluate the pathological findings of the boundary zone between the tumor and adjacent normal brain in glioblastoma patients undergoing simultaneous double staining with 5-ALA and Fl-Na during surgery. Eight patients received 5-ALA (20 mg/kg orally) before the induction of general anesthesia, and Fl-Na (20 mg/kg) was administered intravenously before the dural incision was performed. The tumor bulk was removed under the guidance of Fl-Na staining alone using conventional white light. Subsequently, residual tumor was removed under the guidance of both fluorescent agents within functionally safe limits until both were visibly undetectable. Twenty specimens exhibiting different staining intensities of both agents were obtained. The vessel index (VI) was calculated from CD31 immunohistochemistry (IHC) samples. Boundary zone tumor cells were detected by IHC for olig2, and were expressed as the olig2 index (OLI). The VI was significantly higher in Fl-Na-positive areas than in Fl-Na-negative areas (p = 0.0005). In contrast, the OLI was significantly higher in 5-ALA-positive areas than in 5-ALA-negative areas (p = 0.0149). 5-ALA-positive/Fl-Na negative areas were observed in 7 patients. These findings indicate that Fl-Na accumulates in areas with a disrupted blood-brain barrier, and that 5-ALA fluorescence is dependent on tumor cell protoporphyrin IX metabolism. In conclusion, 5-ALA was better for detecting tumor cells in the boundary zone than was Fl-Na. Of note, tumor cells existed outside the fluorescence-stained boundaries of both agents.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) promotes the progression of brain glioblastoma via Na+/K+-ATPase.

Glycoprotein nonmetastatic melanoma protein B (GPNMB), which is involved in invasion and metastasis, was found to be overexpressed in various cancers. High levels of GPNMB and Na+/K+-ATPase α subunits are associated with a poor prognosis in glioblastoma patients. We showed that GPNMB interacts with Na+/K+-ATPase α subunits to activate PI3K/Akt and MEK/ERK pathways. However, it remains unclear whether the interaction of GPNMB and Na+/K+-ATPase α subunits is involves in progression of glioma. The tumor size induced by the injection of glioma GL261 cells was larger in transgenic mice overexpressing GPNMB when compared with wild-type mice. Additionally, the interaction of GPNMB and Na+/K+-ATPase α subunits was identified in the murine glioma model and in the tumors of glioblastoma patients. Ouabain, a Na+/K+-ATPase inhibitor, suppressed the glioma growth induced by the injection of glioma cells in the transgenic mice overexpressing GPNMB and blocked the GPNMB-induced migration of glioma cells. These findings indicate that GPNMB promotes glioma growth via Na+/K+-ATPase α subunits. Thus, the interaction between GPNMB and Na+, K+-ATPase α subunits represents a novel therapeutic target for the treatment of brain glioblastomas.

[Monitored Anesthesia Care for Deep Brain Stimulation and Embolization of Brain Arteriovenous Malformation].

The aim of monitored anesthesia care (MAC) in neurosurgery and interventional neuroradiology is to provide optimal surgical conditions including patient immobility and comfort, facilitate intraoperative neuromonitoring, and rapidly treat any complication. The anesthetist has a crucial role in facilitating procedures, and this requires an understanding of specific procedures, their potential complications, and their management. Choice of anesthetic technique varies between centers with little data to support any specific technique. Dexmedetomidine is useful as a sedative and hypnotic for patients undergoing procedures without the need for tracheal intubation. We usually use dexmedetomidine in MAC.

Bevacizumab treatment leads to observable morphological and metabolic changes in brain radiation necrosis.

We investigated morphological and metabolic changes of radiation necrosis (RN) of the brain following bevacizumab (BEV) treatment by using neuroimaging. Nine patients with symptomatic RN, who had already been treated with radiation therapy for malignant brain tumors (6 glioblastomas, 1 anaplastic oligodendroglioma, and 2 metastatic brain tumors), were enrolled in this prospective clinical study. RN diagnosis was neuroradiologically determined with Gd-enhanced MRI and 11C-methionine positron emission tomography (MET-PET). RN clinical and radiological changes in MRI, magnetic resonance spectroscopy (MRS) and PET were assessed following BEV therapy. Karnofsky performance status scores improved in seven patients (77.8 %). Both volumes of the Gd-enhanced area and FLAIR-high area from MRI decreased in all patients after BEV therapy and the mean size reduction rates of the lesions were 80.0 and 65.0 %, respectively. MRS, which was performed in three patients, showed a significant reduction in Cho/Cr ratio after BEV therapy. Lesion/normal tissue (L/N) ratios in MET- and 11C-choline positron emission tomography (CHO-PET) decreased in 8 (89 %) and 9 patients (100 %), respectively, and the mean L/N ratio reduction rates were 24.4 and 60.7 %, respectively. BEV-related adverse effects of grade 1 or 2 (anemia, neutropenia and lymphocytopenia) occurred in three patients. These results demonstrated that BEV therapy improved RN both clinically and radiologically. BEV therapeutic mechanisms on RN have been suggested to be related not only to the effect on vascular permeability reduction by repairing the blood-brain barrier, but also to the effect on suppression of tissue biological activity, such as immunoreactions and inflammation.

Posttraumatic epilepsy in chronic disorders of consciousness due to severe traumatic brain injury after traffic accidents.

PURPOSE: To evaluate the clinical state of posttraumatic epilepsy (PTE) in patients with chronic disorders of consciousness (CDC) due to severe traumatic brain injury (STBI) after traffic accidents and clarify the risk factors for seizure occurrence in such patients. METHODS: Two hundred ninety-three patients with CDC due to STBI (mean age at admission [±standard deviation]: 36.4 ± 17.9 years; men: 71.7 %; mean duration of injury to admission: 416 ± 732 days; mean hospitalization time: 899 ± 319 days) were enrolled in this study. We retrospectively investigated the relationship between seizure conditions (type and frequency) and clinical data, including age, sex, pathological types of brain injury, with/without surgical intervention, degree of CDC, and administration of antiseizure medications (ASMs). RESULTS: Overall, 52.9 % (n = 155/293) and 64.2 % of the patients (n = 183/of 285 patients surviving at discharge) were administered ASMs at admission and discharge, respectively. One hundred thirty-two patients (45.1 %) experienced epileptic seizures during hospitalization, and the mean seizure frequency was 4.0 ± 0.4 times per year. In multivariate analysis, significant and independent risk factors of seizure occurrence were revealed to be male sex, high National Agency for Automotive Safety and Victims' Aid score, hypoxic encephalopathy, and history of the neurosurgical operations. CONCLUSION: The high prevalence of PTE in patients with CDC due to STBI, and the significant and independent risk factors for seizure occurrence in the chronic clinical phase were revealed. We expect that this study will aid toward improving clinical assessment and management of epileptic seizures in the population.

Predicting Isocitrate Dehydrogenase Status in Non-Contrast-Enhanced Adult-Type Astrocytic Tumors Using Diffusion Tensor Imaging and 11C-Methionine, 11C-Choline, and 18F-Fluorodeoxyglucose PET.

We aimed to differentiate the isocitrate dehydrogenase (IDH) status among non-enhanced astrocytic tumors using preoperative MRI and PET. We analyzed 82 patients with non-contrast-enhanced, diffuse, supratentorial astrocytic tumors (IDH mutant [IDH-mut], 55 patients; IDH-wildtype [IDH-wt], 27 patients) who underwent MRI and PET between May 2012 and December 2022. We calculated the fractional anisotropy (FA) and mean diffusivity (MD) values using diffusion tensor imaging. We evaluated the tumor/normal brain uptake (T/N) ratios using 11C-methionine, 11C-choline, and 18F-fluorodeoxyglucose PET; extracted the parameters with significant differences in distinguishing the IDH status; and verified their diagnostic accuracy. Patients with astrocytomas were significantly younger than those with glioblastomas. The following MRI findings were significant predictors of IDH-wt instead of IDH-mut: thalamus invasion, contralateral cerebral hemisphere invasion, location adjacent to the ventricular walls, higher FA value, and lower MD value. The T/N ratio for all tracers was significantly higher for IDH-wt than for IDH-mut. In a composite diagnosis based on nine parameters, including age, 84.4% of cases with 0-4 points were of IDH-mut; conversely, 100% of cases with 6-9 points were of IDH-wt. Composite diagnosis using all parameters, including MRI and PET findings with significant differences, may help guide treatment decisions for early-stage gliomas.

Brainstem volume, diffusion, and metabolism are associated with chronic consciousness disorders after traumatic brain injury.

BACKGROUND AND PURPOSE: We aimed to identify reliable neuroradiological features of the brainstem reflecting the neurological symptoms of patients with chronic disorders of consciousness (DOCs) due to severe traumatic brain injury (TBI). METHODS: We retrospectively examined 86 patients with chronic DOCs due to severe TBI caused by automobile accidents. We studied the relationships among (1) neurological symptoms, including consciousness level, (2) integrated cognitive/physical condition, and (3) neuroradiological features of the brainstem (brainstem volume on MRI, fractional anisotropy [FA] value in the brainstem, and standardized uptake value [SUV] of 18F-fluorodeoxyglucose [FDG] on positron emission tomography in the brainstem). RESULTS: Brainstem volume was significantly larger and FA values were significantly higher in patients with a better level of consciousness. However, brainstem volumes were significantly decreased and the maximum SUV (SUVmax ) of FDG significantly increased at 2 years following admission regardless of the level of consciousness at admission. The brainstem volume was significantly larger and the FA value and SUVmax of FDG were significantly higher in patients with better National Agency for Automotive Safety and Victims' Aid (NASVA) scores at admission. The decrease in the brainstem volume was significantly minimized and the SUVmax of FDG significantly increased in patients with more improvement in the NASVA score 2 years after admission. CONCLUSIONS: The volume, FA value, and SUVmax of FDG of the brainstem are important neuroradiological features associated with the neurological conditions of patients with chronic DOCs due to severe TBI.

Methionine-PET to differentiate between brain lesions appearing similar on conventional CT/MRI scans.

BACKGROUND AND PURPOSE: 11 C-Methionine (MET)-PET is a useful tool in neuro-oncology. This study aimed to examine whether a combination of diagnostic variables associated with MET uptake could help distinguish between brain lesions that are often difficult to discriminate in conventional CT and MRI. METHODS: MET-PET was assessed in 129 patients with glioblastoma multiforme, primary central nervous lymphoma, metastatic brain tumor, tumefactive multiple sclerosis, or radiation necrosis. The accuracy of the differential diagnosis was analyzed using five diagnostic characteristics in combination: higher maximum standardized uptake value (SUV) of MET in the lesion/the mean normal cortical SUV of MET ratio, overextension beyond gadolinium, peripheral pattern indicating abundant MET accumulation in the peripheral region, central pattern denoting abundant MET accumulation in the central region, and dynamic-up suggesting increased MET accumulation during dynamic study. The analysis was conducted on sets of two of the five brain lesions. RESULTS: Significant differences in the five diagnostic traits were observed among the five brain lesions, and differential diagnosis could be achieved by combining these diagnostic features. The area under the curve between each set of two of the five brain lesions using MET-PET features ranged from .85 to 1.0. CONCLUSIONS: According to the findings, combining the five diagnostic criteria could help with the differential diagnosis of the five brain lesions. MET-PET is an auxiliary diagnostic technique that could help in distinguishing these five brain lesions.

Combining methionine-PET and MRI fluid-attenuated inversion-recovery mismatch to determine glioma molecular subtype.

BACKGROUND AND PURPOSE: 11 C-methionine (MET)-PET is a useful tool in neuro-oncology. The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign on MRI is a characteristic finding in lower grade gliomas with isocitrate dehydrogenase (IDH) mutations and the absence of the 1p/19q codeletion; however, the T2-FLAIR mismatch sign has low sensitivity in differentiating gliomas and does not aid in identifying glioblastomas with IDH mutations. We therefore investigated the efficacy of the combination of the T2-FLAIR mismatch sign and MET-PET for accurately determining the molecular subtype of gliomas of all grades. METHODS: The present study comprised 208 adult patients diagnosed with supratentorial glioma confirmed by molecular genetics and histopathology. The ratio of the maximum lesion MET accumulation to the mean normal frontal cortex MET accumulation (T/N) was measured. The presence or absence of the T2-FLAIR mismatch sign was determined. The presence or absence of the T2-FLAIR mismatch sign and the MET T/N ratio were compared between glioma subtypes to evaluate individual and combined utility in identifying gliomas with IDH mutations and no 1p/19q codeletion (IDHmut-Noncodel) or gliomas with IDH mutations (IDHmut). RESULTS: The addition of MET-PET to MRI for the presence of the T2-FLAIR mismatch sign improved diagnostic accuracy, with the area under the curve values increasing from .852 to .871 for IDHmut-Noncodel and from .688 to .808 for IDHmut. CONCLUSIONS: The combination of the T2-FLAIR mismatch sign and MET-PET may provide improved diagnostic utility in differentiating gliomas according to molecular subtype, particularly in determining IDH mutation status.

Resection of positive tissue on methionine-PET is associated with improved survival in glioblastomas.

BACKGROUND AND PURPOSE: The volume of excised tumor in contrast-enhanced areas evaluated via magnetic resonance imaging is known to have a strong influence on the survival of patients with glioblastoma (GBM). In this study, we investigated the effect of tumor resection on the survival of patients with GBM in the 11 C-methionine (MET) accumulation area using MET-positron emission tomography (MET-PET). METHODS: A total of 26 patients (median age, 69 years; 15 males) who had undergone tumor resection and MET-PET before and after surgery, after being newly diagnosed with GBM, were included in the study. MET-PET before and after tumor resection were compared. The association between the decrease in the maximum standardized uptake value (SUV) of the tumor divided by the normal cortical mean SUV (%; ΔT/N), the MET extent of resection (MET-EOR) from the % reduction in the MET accumulation area (%), and residual MET accumulation area (in cm3 ; MET-residual tumor volume [RTV]), as well as the survival time of patients with GBM, were evaluated via univariate analysis. RESULTS: ΔT/N were positively associated with survival (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.97-0.99], p = .02). MET-RTV revealed a negative association with survival (HR, 1.02 [95% CI, 1.01-1.04], p = .04). Additionally, MET-EOR showed a strong trend with survival (HR, 0.99 [95% CI, 0.97-1.01], p = .06). CONCLUSIONS: Surgical resection of MET-accumulated areas in GBM significantly prolongs the survival of patients with GBM. However, a prospective large-scale multicenter study is needed to confirm our findings.

Differentiation of astrocytoma between grades II and III using a combination of methionine positron emission tomography and magnetic resonance spectroscopy.

Objective: This study aimed to establish a method for differentiating between grades II and III astrocytomas using preoperative imaging. Methods: We retrospectively analyzed astrocytic tumors, including 18 grade II astrocytomas (isocitrate dehydrogenase (IDH)-mutant: IDH-wildtype = 8:10) and 56 grade III anaplastic astrocytomas (37:19). We recorded the maximum methionine (MET) uptake ratios (tumor-to-normal: T/N) on positron emission tomography (PET) and three MRS peak ratios: choline (Cho)/creatine (Cr), N-acetyl aspartate (NAA)/Cr, and Cho/NAA, between June 2015 and June 2020. We then evaluated the cut-off values to differentiate between grades II and III. We compared the grading results between contrast enhancement effects on MR and combinational diagnostic methods (CDM) on a scatter chart using the cutoff values of the T/N ratio and MRS parameters. Results: The IDH-mutant group showed significant differences in the Cho/NAA ratio between grades II and III using univariate analysis; however, multiple regression analysis results negated this. The IDH-wildtype group showed no significant differences between the groups. Contrast enhancement effects also showed no significant differences in IDH status. Accordingly, regardless of the IDH status, no statistically independent factors differentiated between grades II and III. However, CDMs showed higher sensitivity and negative predictive value in distinguishing them than MRI contrast examinations for both IDH statuses. We demonstrated a significantly higher diagnostic rate of grade III than of grade II with CDM, which was more striking in the IDH-mutant group than in the wild-type group. Conclusions: CDM could be valuable in differentiating between grade II and III astrocytic tumors.

Significance of target location relative to the depth from the brain surface and high-dose irradiated volume in the development of brain radionecrosis after micromultileaf collimator-based stereotactic radiosurgery for brain metastases.

The objective of this study was to investigate the factors that potentially lead to brain radionecrosis (RN) after micromultileaf collimator-based stereotactic radiosurgery (SRS) for brain metastases. We retrospectively evaluated 131 lesions with a minimum follow-up of 6 months, 43.5% of which received prior whole-brain radiotherapy (WBRT). The three-tiered location grade (LG) was defined, as follows, for each target by considering mainly the depth from the brain surface: grade 1 (superficial), involving the region at a depth of ≤5 mm from the brain surface; grade 2 (deep), located at a depth of >5 mm from the brain surface; and grade 3 (central), located in the brainstem, cerebellar peduncle, diencephalon, or basal ganglion. The predictive factors for RN, including high-dose irradiated isodose volumes (IIDVs) and LG, were evaluated by univariate and multivariate analysis. Symptomatic RN (S-RN) and asymptomatic RN (A-RN) were observed in 8.4% and 6.9% of cases, respectively. Multivariate analysis indicated that the significant factors for both types of RN were LG, V12 Gy, and V22 Gy in all cases; V22 Gy and LG for the non-WBRT cases; and V15 Gy and LG for the WBRT cases. For the non-WBRT cases, the cutoff values of V22 Gy were 2.62 and 2.14 cm(3) for S-RN and both RN, respectively. For the WBRT cases, the cutoff values of V15 Gy were 5.61 and 5.20 cm(3) for S-RN and both RN, respectively. In addition to the IIDV data, LG helps predict the risk of RN. High-dose IIDV, V22 Gy, was also significantly correlated with RN, particularly for patients treated with SRS alone.

Evaluation of brain tumors using dynamic 11C-methionine-PET.

The aim of this study is to assess whether dynamic imaging of (11)C-methionine (MET) uptake on positron emission tomography (PET) is useful for the differential diagnosis of brain tumor histology. Regional MET uptake in static brain PET scans from three consecutive phases (5-15, 15-25, and 25-35 min) after intravenous injection were measured in 144 patients with brain tumors. Regions of interest (ROI) were placed in the pituitary gland, confluence, choroid plexus, coronal radiation, brainstem, frontal cortex, parietal cortex, cerebellum, and brain tumors. The standard uptake value (SUV) of the ROIs in the normal brain structures and brain tumors were measured, and the mean MET SUV region/normal frontal lobe cortex uptake ratio (R/N ratio) of the normal brain structures and the maximum MET SUV tumor/normal frontal cortex uptake ratio (T/N ratio) were evaluated semi-quantitatively. There were significant dynamic declines of the mean MET R/N ratio in the normal pituitary gland and confluence; however, there were significant dynamic increases in white matter. Significant dynamic decrease of the maximum MET T/N ratio was seen in meningiomas and oligodendrocytic tumors, whereas significant dynamic increase was seen in glioblastomas and malignant lymphomas. Dynamic changes of MET uptake vary significantly with the normal brain structures and brain tumor histology. These results suggest that MET-PET may be useful in the differential diagnosis of brain tumors.

Radiological Prediction of Isocitrate Dehydrogenase (IDH) Mutational Status and Pathological Verification for Lower-Grade Astrocytomas.

Background and objective The isocitrate dehydrogenase (IDH) status of patients with World Health Organization (WHO) grade II or III astrocytoma is essential for understanding its biological features and determining therapeutic strategies. This study aimed to use radiological analysis to predict the IDH status of patients with lower-grade astrocytomas and to verify the pathological implications. Methods In this study, 47 patients with grade II (17 cases) or III astrocytomas (30 cases), based on 2016 WHO Classification, underwent methionine (MET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) on the same day between January 2013 and June 2020. The patients were retrospectively assessed. Immunohistochemistry showed 23 cases of IDH-mutant and 24 of IDH-wildtype. Based on fluid-attenuated recovery inversion (FLAIR)/T2 imaging, three doctors blinded to clinical data independently allocated 18 patients to the clear boundary group between the tumor and the normal brain and 29 to the unclear boundary group. The peak ratios of N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and Cho/NAA and the tumor-to-normal region (T/N) ratio for maximum accumulation in MET-PET were calculated. For statistical analysis, Fisher's exact test was used to assess associations between two variables, and the Mann-Whitney U test to compare the values between the IDH-wildtype and IDH-mutant groups. The optimal cut-off values of MET T/N ratio and MRS parameters for discriminating IDH-wildtype from IDH-mutant were obtained using receiver operating characteristics curves. Results The unclear boundary group had significantly more IDH-wildtype cases than the clear boundary group (P<0.001). The IDH-wildtype group had significantly lower Cho/Cr (<1.84) and Cho/NAA (<1.62) ratios (P=0.02 and P=0.047, respectively) and a higher MET T/N ratio (>1.44, P=0.02) than the IDH-mutant group. The odds for the IDH-wildtype were 0.22 for patients who fulfilled none of the four criteria, including boundary status and three ratios, and 0.9 for all four criteria. Conclusions These results suggest that the combination of MRI, MRS, and MET-PET examination could be helpful for the prediction of IDH status in WHO grade II/III gliomas.