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Background: Brain metastasis (BrM) is prevalent among patients with NSCLC, and surgical resection of BrM constitutes a promising treatment strategy for local management and histopathological diagnosis, although it is offered for a select group of patients. Limited information exists concerning the improvement in performance status (PS) following BrM resection or the outcomes stratified by subsequent systemic therapy., Methods: We conducted a retrospective single-center cohort study including NSCLC patients with surgically resected BrM and focused on the improvement in PS and subsequent therapy after BrM resection., Results: 71 patients were included, and the median overall survival was 18.3 months (95% confidence interval [95% CI]: 8.7, not reached). Patients with NSCLC who underwent surgical resection of BrM showed significant improvement in PS (18% and 39% showed ECOG PS of 0-1, before and after BrM resection, respectively [p = 0.006]), and patients with PS improvement were younger than those with PS unimprovement (median, 62 years versus 66 years; p = 0.041). Regarding subsequent systemic therapy after BrM resection, 21 patients (30%) received cytotoxic chemotherapy, 14 patients (20%) received tyrosine kinase inhibitors (TKIs), 3 patients (4%) received immune checkpoint inhibitors (ICIs), and 21 patients (30%) received no subsequent therapy. The survival outcomes of patients stratified by subsequent systemic treatments suggested the tendency that those who received TKI or ICI showed better survival outcomes, although a small number of patients hindered statistical comparisons., Conclusions: We describe the outcomes of patients with NSCLC who underwent surgical resection of BrM, revealing that younger patients were more likely to anticipate improvement in PS, and patients who received TKI or ICI after BrM resection tended to exhibit a more preferable prognosis., (© 2024. The Author(s).)

Purpose: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indications, we aimed to analyze the clinical significance of preoperative LME of the brainstem in glioblastoma., Methods: We retrospectively collected clinical and radiological data from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020., Results: Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. In comparison with tumors without LME, tumor size was significantly associated with the preoperative LME of the brainstem (p = 0.016). In addition, there was a trend toward significance for a relationship between deep tumor location and preoperative LME of the brainstem (p = 0.058). Notably, among six patients who underwent surgical resection for glioblastoma with LME of the brainstem, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. However, this LME disappearance was not observed after biopsy or chemoradiotherapy., Conclusions: These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale and Objectives: To evaluate the performance of a machine learning method to differentiate malignant from benign soft tissue tumors based on textural features on multiparametric magnetic resonance imaging (mpMRI)., Materials and Methods: We enrolled 163 patients with soft tissue tumors whose diagnosis was pathologically proven (71 malignant, 92 benign). All patients underwent mpMRI. Twelve histographic and textural parameters were assessed on T1-weighted imaging (T1WI), T2-weighted imaging, diffusion-weighted imaging, apparent diffusion coefficient maps, and contrast-enhanced T1WI imaging. We compared mean signals of all sequences from the malignant and benign tumors using Welch's t-test. Prediction models were developed via a machine learning technique (support vector machine) using textural features of each sequence, clinical information (sex + age + tumor size), and the combined model incorporating all features. Areas under the receiver operating characteristic curves (AUCs) of these models were calculated using fivefold cross validation., Results: The diagnostic ability of clinical information model (AUC 0.85) was not inferior to the model with textural features of each sequence (AUC 0.79-0.84). The combined model showed the highest diagnostic ability (AUC 0.89). The AUC of the combined model (0.89) was comparable to those of two board-certified radiologists (0.89 and 0.87)., Conclusions: Machine learning methods based on textural features on mpMRI and clinical information offer adequate diagnostic performance to differentiate between malignant and benign soft tissue tumors., (Copyright © 2022. Published by Elsevier Inc.)

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan-Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Uterine malignant tumors (uterine cervical carcinoma [UCC], uterine endometrial carcinoma, and uterine sarcoma) are common in women. Brain metastases from uterine malignant tumors are rare, but its incidence has been increasing. The present study aimed to investigate the characteristics of brain metastases from uterine malignant tumors, evaluate predictive factors, and assess the efficacy of Gamma Knife surgery (GKS) for metastases from uterine malignant tumors., Methods: We retrospectively reviewed the records of patients with brain metastases from uterine malignant tumors treated at Tokyo Gamma Unit Center from 2005 to 2017., Results: We identified 37 patients: 16 had UCC, 12 had uterine endometrial carcinoma, and 9 had uterine sarcoma. Their median age at diagnosis of brain metastases was 54.0 years. The median interval from diagnosis of uterine malignant tumor to brain metastases was 21.0 months, the median number of brain metastases was 3.0, and the median Karnofsky Performance Status at first GKS was 80%. The median survival after first GKS was 6.0 months. All patients had other metastases. Six-month and 1-year survival after first GKS were 48.9% and 32.6%, respectively, and the tumor control rate at 6 months after GKS was 90.8%. Brain metastases from UCC were significantly correlated with good tumor control (P = 0.024). Multivariate analysis determined that Karnofsky Performance Status was significantly associated with patient survival (P = 0.001)., Conclusions: The results of our study suggest that GKS is an acceptable choice for controlling brain metastases from uterine malignant tumors. In particular, GKS provides excellent local control for metastases from UCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Neurite orientation dispersion and density imaging (NODDI) is a new technique that applies a three-diffusion-compartment biophysical model. We assessed the usefulness of NODDI for the differentiation of glioblastoma from solitary brain metastasis., Methods: NODDI data were prospectively obtained on a 3T magnetic resonance imaging (MRI) scanner from patients with previously untreated, histopathologically confirmed glioblastoma (n = 9) or solitary brain metastasis (n = 6). Using the NODDI Matlab Toolbox, we generated maps of the intra-cellular, extra-cellular, and isotropic volume (VIC, VEC, VISO) fraction. Apparent diffusion coefficient - and fraction anisotropy maps were created from the diffusion data. On each map we manually drew a region of interest around the peritumoral signal-change (PSC) - and the enhancing solid area of the lesion. Differences between glioblastoma and metastatic lesions were assessed and the area under the receiver operating characteristic curve (AUC) was determined., Results: On VEC maps the mean value of the PSC area was significantly higher for glioblastoma than metastasis (P < 0.05); on VISO maps it tended to be higher for metastasis than glioblastoma. There was no significant difference on the other maps. Among the 5 parameters, the VEC fraction in the PSC area showed the highest diagnostic performance. The VEC threshold value of ≥ 0.48 yielded 100% sensitivity, 83.3% specificity, and an AUC of 0.87 for differentiating between the two tumor types., Conclusions: NODDI compartment maps of the PSC area may help to differentiate between glioblastoma and solitary brain metastasis., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Brain metastases (BM) are one of the strongest negative prognostic factors in patients with non-small cell lung cancer (NSCLC). Molecularly targeted agents are standard of care for NSCLC patients with a driver mutation; however, their efficacy in patients with BM is not fully understood because patients with BM are usually excluded from clinical studies. This study investigated the current management and outcomes of newly diagnosed NSCLC patients with BM in Japanese clinical practice, focusing on their driver mutation status., Patients and Methods: We enrolled newly diagnosed, treatment-naïve NSCLC patients with BM between January 2012 and December 2015 from 4 institutions in Japan. The medical records of each patient were retrospectively reviewed, and the treatment details and outcomes were evaluated., Results: In total, 203 patients with BM were enrolled in this study and 73 (36%) were neurologically symptomatic. Regarding initial treatment, 110 patients (54%) received local therapy, including radiotherapy and surgery, whereas 77 (38%) received systemic therapy. The median overall survival (OS) was 14.3 months for all patients, and it was significantly longer among patients with a driver mutation (28.9 months; 95% confidence interval [CI], 20.9-41.0) than among patients without a driver mutation (9.9 months; 95% CI, 7.0-13.4) (hazard ratio [HR] 0.39; 95% CI, 0.27-0.57; p < 0.001). Multivariate analysis identified performance status (HR 1.78; 95% CI, 1.16-2.72; p = 0.009) and driver mutation status (HR 0.27; 95% CI, 0.17-0.44; p < 0.001) as significant prognostic factors. No significant difference in OS was noted according to the type of initial treatment, i.e., local versus systemic., Conclusion: The median OS of patients with a driver mutation was longer than 2 years, even of patients with BM, and it was significantly longer than that of patients without a driver mutation. Driver mutation status, in addition to performance status, was a significant prognostic factor in NSCLC patients with BM., (© 2020 S. Karger AG, Basel.)

Purpose/objective(s): Radiosurgery plus whole-brain radiotherapy (WBRT) has been reported to be useful for patients with ≤ 4 brain metastases (BM), but we hypothesized that similar treatment may be applicable to patients with ≥ 5 BM with or without meningeal dissemination. The purpose of this study was to evaluate the efficacy and toxicity of low-dose Gamma Knife (GK) followed by WBRT for patients with advanced BM., Materials/methods: Major eligibility criteria for this phase II study were: (1) ≥ 5 BM with or without meningeal dissemination and (2) the largest tumor diameter ≤ 4 cm. During 2013-2016, 40 patients (13 men and 27 women) entered the study. Nineteen had meningeal dissemination. The GK dose was 12 Gy at the periphery when the longest diameter was 3-4 cm and 14 Gy when it was < 3 cm. The WBRT dose to the isocenter was 30 Gy in 10 fractions, or 37.5 Gy in 15 fractions for two patients, with an expected survival of > 12 months. The median number of target BM was 17.5., Results: After GK plus WBRT for 40 patients, 31 did not develop further intracranial recurrence until death or last follow-up, whereas 9 developed recurrence. With a follow-up period up to 24 months, the overall survival rate was 36% at 12 months and median survival time was 8 months. The cumulative incidence of intracranial recurrence was 25% at 12 months. Toxicity was considered acceptable., Conclusion: Treatment with low-dose GK followed by WBRT for advanced-stage BM appeared to contribute to local control.

Introductions: [ N -methyl-C-11] α -Methylaminoisobutyric acid (MeAIB) is an artificial amino acid radiotracer used for PET study, which is metabolically stable in vivo. In addition, MeAIB is transported by system A neutral amino acid transport, which is observed ubiquitously in all types of mammalian cells. It has already been shown that MeAIB-PET is useful for malignant lymphoma, head and neck cancers, and lung tumors. However, there have been no reports evaluating the usefulness of MeAIB-PET in the diagnosis of brain tumors. The purpose of this study is to investigate the efficacy of system A amino acid transport PET imaging, MeAIB-PET, in clinical brain tumor diagnosis compared to [S-methyl-C-11]-L-methionine (MET)-PET., Methods: Thirty-one consecutive patients (male: 16, female: 15), who were suspected of having brain tumors, received both MeAIB-PET and MET-PET within a 2-week interval. All patients were classified into two groups: Group A as a benign group, which included patients who were diagnosed as low-grade astrocytoma, grade II or less, or other low-grade astrocytoma ( n =12) and Group B as a malignant group, which included patients who were diagnosed as anaplastic astrocytoma, glioblastoma multiforme (GBM), or recurrent GBM despite prior surgery or chemoradiotherapy ( n =19). PET imaging was performed 20 min after the IV injection of MeAIB and MET, respectively. Semiquantitative analyses of MeAIB and MET uptake using SUVmax and tumor-to-contralateral normal brain tissue ( T / N ) ratio were evaluated to compare these PET images. ROC analyses for the diagnostic accuracy of MeAIB-PET and MET-PET were also calculated., Results: In MeAIB-PET imaging, the SUVmax was 1.20 ± 1.29 for the benign group and 2.94 ± 1.22 for the malignant group ( p < 0.005), and the T / N ratio was 3.77 ± 2.39 for the benign group and 16.83 ± 2.39 for the malignant group ( p < 0.001). In MET-PET, the SUVmax was 3.01 ± 0.94 for the benign group and 4.72 ± 1.61 for the malignant group ( p < 0.005), and the T / N ratio was 2.64 ± 1.40 for the benign group and 3.21 ± 1.14 for the malignant group ( n.s. ). For the analysis using the T / N ratio, there was a significant difference between the benign and malignant groups with MeAIB-PET with p < 0.001. The result of ROC analysis using the T / N ratio indicated a better diagnosis accuracy for MeAIB-PET for brain tumors than MET-PET ( p < 0.01)., Conclusions: MeAIB, a system A amino acid transport-specific radiolabeled agents, could provide better assessments for detecting malignant type brain tumors. In a differential diagnosis between low-grade and high-grade astrocytoma, MeAIB-PET is a useful diagnostic imaging tool, especially in evaluations using the T / N ratio., Clinical Trial Registration: This trial was registered with UMIN000032498.

Background: Brain metastases from hepatocellular carcinoma (HCC) are rare, but their incidence is increasing because of developments in recent therapeutic advances. The purpose of this study was to investigate the characteristics of brain metastases from HCC, to evaluate the predictive factors, and to assess the efficacy of gamma knife surgery (GKS)., Method: A retrospective study was performed on patients with brain metastases from HCC who were treated at Tokyo Gamma Unit Center from 2005 to 2014., Results: Nineteen patients were identified. The median age at diagnosis of brain metastases was 67.0 years. Fifteen patients were male and four patients were female. Six patients were infected with hepatitis B virus (HBV). Two patients were infected with hepatitis C virus (HCV). Eleven patients were not infected with HBV or HCV. The median interval from the diagnosis of HCC to brain metastases was 32.0 months. The median number of brain metastases was two. The median Karnofsky performance score at first GKS was 70. The median survival time following brain metastases was 21.0 weeks. Six-month and 1-year survival rates were 41.2 and 0%, respectively. One month after GKS, no tumor showed progressive disease. The HBV infection (positive vs. negative) was significantly associated with survival according to univariate analysis (p = 0.002)., Conclusions: The patients having brain metastases from HCC had poor prognosis and low performance state. Therefore, GKS is an acceptable option for controlling brain metastases from HCC because GKS is noninvasive remedy and local control is reasonable.

Objective: The purpose of this study was to determine whether combined diffusion-weighted imaging and dynamic susceptibility contrast-enhanced perfusion-weighted imaging magnetic resonance imaging can be used to differentiate between common malignant brain tumors, including lymphomas and high-grade gliomas., Methods: We evaluated 87 patients with histologically confirmed brain tumors, including 33 primary central nervous system lymphomas (PCNSLs) and 54 glioblastomas (GBMs). All patients underwent conventional magnetic resonance imaging, diffusion-weighted imaging, and perfusion-weighted imaging before surgical removal of the lesion or stereotactic biopsy., Results: The maximum relative cerebral blood volume (rCBV) ratios of GBMs were significantly higher than those of PCNSLs (P < 0.0001). The maximum rCBVs helped to distinguish PCNSLs from GBMs with 97.0% sensitivity, 90.7% specificity, and 0.98 area under the curve. The minimum apparent diffusion coefficients (ADCs) of PCNSLs were significantly lower than those of GBMs (P < 0.0001). At an rCBV cutoff value of 4.0 and a minimum ADC of 1.0 × 10 -3 mm 2 /second, it was possible to differentiate between PCNSLs and GBMs., Conclusions: The combination of rCBV and ADC can facilitate the differentiation between PCNSLs and GBMs., (Copyright © 2017. Published by Elsevier Inc.)

OBJECTIVE The neurological prognostic score (NPS) was recently proposed as a means for predicting neurological outcomes, such as the preservation of neurological function and the prevention of neurological death, in brain metastasis patients treated with Gamma Knife radiosurgery (GKRS). NPS consists of 2 groups: Group A patients were expected to have better neurological outcomes, and Group B patients were expected to have poorer outcomes. NPS robustness was tested in various situations. METHODS In total, 3040 patients with brain metastases that were treated with GKRS were analyzed. The cumulative incidence of the loss of neurological function independence (i.e., neurological deterioration) was estimated using competing risk analysis, and NPS was compared between Groups A and B by employing Gray's model. NPS was tested to determine if it can be applied to 5 cancer categories-non-small cell lung cancer, small cell lung cancer, gastrointestinal tract cancer, breast cancer, and other cancers-as well as if it can be incorporated into the 5 major grading systems: recursive partitioning analysis (RPA), score index for stereotactic radiosurgery (SIR), basic score for brain metastases (BSBM), graded prognostic assessment (GPA), and modified-RPA (M-RPA). RESULTS There were 2263 patients in NPS Group A and 777 patients in Group B. Neurological deterioration was observed in 586 patients (19.2%). The cumulative incidences of neurological deterioration were 9.5% versus 21.0%, 14.1% versus 25.4%, and 17.6% versus 27.8% in NPS Groups A and B at 1, 2, and 5 years, respectively. Significant differences were detected between the NPS groups in all cancer categories. There were significant differences between NPS Groups A and B for all classes in terms of the BSBM, GPA, and M-RPA systems, but the differences failed to reach statistical significance in terms of RPA Class I and SIR Class 0 to 3. CONCLUSIONS The NPS was verified as being highly applicable to all cancer categories and almost all classes for the 5 grading systems in terms of neurological function independence. This NPS system appears to be quite robust in various situations for brain metastasis patients treated with GKRS.

Purpose: We aimed to determine whether 3T diffusion-weighted imaging (DWI) has an additive value relative to contrast-enhanced MR imaging for the detection of disseminated lesions in patients with primary malignant brain tumors., Methods: We included consecutive 12 patients with nodular disseminated lesions of primary malignant brain tumors that were confirmed by surgery or follow-up MR imaging. All underwent conventional MR imaging, DWI at b = 1000 and 3000 s/mm 2 , post-contrast T 1 -weighted and 3D gradient-echo imaging at 3T. For the largest lesion per person, two radiologists independently evaluated the presence of additional information on DWI compared with postcontrast MR images using a 4-point scoring system. On DW images, one radiologist measured the lesion-to-brain contrast ratio (LBCR)., Results: Compared with postcontrast studies, radiologists 1 and 2, respectively, assigned more apparent lesion conspicuity in 2 (17%) and 1 (8%) DWI at b = 1000 s/mm 2 and 4 (33%) and 5 (42%) DWI at b = 3000 s/mm 2 studies. For one of them, the mean score was significantly higher for b = 3000 s/mm 2 than b = 1000 s/mm 2 (P < 0.05). Interobserver agreement for DWI at b = 1000 s/mm 2 and b = 3000 s/mm 2 was very good (κ = 0.85; 95% CI, 0.63-1.00) and excellent (κ = 0.93; 95% CI, 0.78-1.00), respectively. The mean LBCR was significantly higher for DWI at b = 3000 s/mm 2 than DWI at b = 1000 s/mm 2 (P < 0.01)., Conclusion: In the detection of disseminated lesions in patients with primary malignant brain tumors, 3T DWI has an additive value relative to contrast-enhanced MR imaging. DWI at b = 3000 s/mm 2 may be more useful than DWI at b = 1000 s/mm 2 .

Purpose: The purpose of the present study was to compare different software algorithms for processing DSC perfusion images of cerebral tumors with respect to i) the relative CBV (rCBV) calculated, ii) the cutoff value for discriminating low- and high-grade gliomas, and iii) the diagnostic performance for differentiating these tumors., Methods: Following approval of institutional review board, informed consent was obtained from all patients. Thirty-five patients with primary glioma (grade II, 9; grade III, 8; and grade IV, 18 patients) were included. DSC perfusion imaging was performed with 3-Tesla MRI scanner. CBV maps were generated by using 11 different algorithms of four commercially available software and one academic program. rCBV of each tumor compared to normal white matter was calculated by ROI measurements. Differences in rCBV value were compared between algorithms for each tumor grade. Receiver operator characteristics analysis was conducted for the evaluation of diagnostic performance of different algorithms for differentiating between different grades., Results: Several algorithms showed significant differences in rCBV, especially for grade IV tumors. When differentiating between low- (II) and high-grade (III/IV) tumors, the area under the ROC curve (Az) was similar (range 0.85-0.87), and there were no significant differences in Az between any pair of algorithms. In contrast, the optimal cutoff values varied between algorithms (range 4.18-6.53)., Conclusions: rCBV values of tumor and cutoff values for discriminating low- and high-grade gliomas differed between software packages, suggesting that optimal software-specific cutoff values should be used for diagnosis of high-grade gliomas.

Background: To treat local recurrence of brain metastases after gamma knife radiosurgery (GKS), we have used fractionated stereotactic radiotherapy (SRT). The purpose of this study was to evaluate the efficacy and toxicity of SRT in these patients., Methods: Fifty locally recurrent metastatic brain tumors in 47 patients were treated with SRT. The median prescribed dose of GKS was 20 Gy at the periphery. The median interval between the GKS (the last session in cases in which multiple GKS procedures were performed) and recurrence was 7.5 (range 1-33) months. Several dose-fractionation protocols were used for SRT, depending on the size and location of the tumor and previous GKS dose. The median prescribed dose of the SRT at the isocenter was 30 Gy with a median of ten fractions., Results: Among the 50 lesions treated with SRT, 26 did not recur locally before the patient's death or the last follow-up examination, and 24 recurred locally. The median follow-up period for the surviving patients was 24 months after the first GKS procedure, and the overall survival rate was 80% at 1 year and 57% at 2 years. The median time to local re-recurrence after the SRT (16 months) was significantly longer than the median interval between the last GKS and recurrence (7.5 months; P < 0.001). Only two patients developed ≥grade 2 radiation necrosis., Conclusions: Stereotactic radiotherapy appeared to be an effective treatment for recurrent metastatic brain tumors and yielded relatively good local control. The associated adverse events were generally acceptable.

Purpose: To assess whether 320-section low-dose dynamic volume computed tomography (320-LDVCT) with adaptive iterative dose reduction (AIDR) adds value to 3-T MRI for the preoperative evaluation of brain tumors., Methods: The study population was comprised of 16 consecutive patients with brain tumors who, in addition to preoperative 3-T MRI, underwent 320-LDVCT with AIDR. Two radiologists independently evaluated the CT and MRI studies; one measured the relative cerebral blood volume (rCBV) in the tumor and contralateral brain on CT and MR perfusion maps. Interobserver agreement was assessed by κ statistics., Results: In 3 of 16 patients (19 %), 320-LDVCT added diagnostic value to 3-T MRI studies with respect to the visualization of feeders (κ = 0.77), and in 12 (75 %) it helped the delineation of venous structures (κ = 0.71) and the relationship between the tumor and adjacent vessels (κ = 0.85). The average standardized rCBV value was 12.2 ± 2.40 (range 0.7-36.6) on MR and 8.80 ± 2.77 (range 0.8-38.0) on CT perfusion studies; the correlation between these values was very strong (r = 0.92, p < 0.0001). According to the neurosurgeons, 320-LDVCT added helpful information for surgery in 4 patients (25 %)., Conclusion: The 320-LDVCT can add value to 3-T MRI for the tumor feeders and relationship between the tumor and adjacent vessels.

Background: Glioblastoma (GBM) may initially respond to treatment with ionizing radiation (IR), but the prognosis remains extremely poor because the tumors invariably recur. Using animal models, we previously showed that inhibiting stromal cell-derived factor 1 signaling can prevent or delay GBM recurrence by blocking IR-induced recruitment of myeloid cells, specifically monocytes that give rise to tumor-associated macrophages. The present study was aimed at determining if inhibiting colony stimulating factor 1 (CSF-1) signaling could be used as an alternative strategy to target pro-tumorigenic myeloid cells recruited to irradiated GBM., Methods: To inhibit CSF-1 signaling in myeloid cells, we used PLX3397, a small molecule that potently inhibits the tyrosine kinase activity of the CSF-1 receptor (CSF-1R). Combined IR and PLX3397 therapy was compared with IR alone using 2 different human GBM intracranial xenograft models., Results: GBM xenografts treated with IR upregulated CSF-1R ligand expression and increased the number of CD11b+ myeloid-derived cells in the tumors. Treatment with PLX3397 both depleted CD11b+ cells and potentiated the response of the intracranial tumors to IR. Median survival was significantly longer for mice receiving combined therapy versus IR alone. Analysis of myeloid cell differentiation markers indicated that CSF-1R inhibition prevented IR-recruited monocyte cells from differentiating into immunosuppressive, pro-angiogenic tumor-associated macrophages., Conclusion: CSF-1R inhibition may be a promising strategy to improve GBM response to radiotherapy., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: Gadobutrol (Gadavist) and gadoteridol (ProHance) have similar macrocyclic molecular structures, but gadobutrol is formulated at a 2-fold higher (1 mol/L versus 0.5 mol/L) concentration. We sought to determine whether this difference impacts morphologic contrast-enhanced MR imaging., Materials and Methods: Two hundred twenty-nine adult patients with suspected or known brain tumors underwent two 1.5T MR imaging examinations with gadoteridol or gadobutrol administered in randomized order at a dose of 0.1 mmol/kg of body weight. Imaging sequences and T1 postinjection timing were identical for both examinations. Three blinded readers evaluated images qualitatively and quantitatively for lesion detection and for accuracy in characterization of histologically confirmed brain tumors. Data were analyzed by using the Wilcoxon signed rank test, the McNemar test, and a mixed model., Results: Two hundred nine patients successfully completed both examinations. No reader noted a significant qualitative or quantitative difference in lesion enhancement, extent, delineation, or internal morphology (P values = .69-1.00). One hundred thirty-nine patients had at least 1 histologically confirmed brain lesion. Two readers found no difference in the detection of patients with lesions (133/139 versus 135/139, P = .317; 137/139 versus 136/139, P = .564), while 1 reader found minimal differences in favor of gadoteridol (136/139 versus 132/139, P = .046). Similar findings were noted for the number of lesions detected and characterization of tumors (malignant/benign). Three-reader agreement for characterization was similar for gadobutrol (66.4% [κ = 0.43]) versus gadoteridol (70.3% [κ = 0.45]). There were no significant differences in the incidence of adverse events (P = .199)., Conclusions: Gadoteridol and gadobutrol at 0.1 mmol/kg of body weight provide similar information for visualization and diagnosis of brain lesions. The 2-fold higher gadolinium concentration of gadobutrol provides no benefit for routine morphologic imaging., (© 2015 by American Journal of Neuroradiology.)

Object: The Basic Score for Brain Metastases (BSBM) proposed by Lorenzoni and colleagues is one of the best grading systems for predicting survival periods after stereotactic radiosurgery (SRS) for brain metastases. However, it includes no brain factors and cannot predict neurological outcomes, such as preservation of neurological function and prevention of neurological death. Herein, the authors propose a modified BSBM, adding 4 brain factors to the original BSBM, enabling prediction of neurological outcomes, as well as of overall survival, in patients undergoing SRS., Methods: To serve as neurological prognostic scores (NPSs), the authors scored 4 significant brain factors for both preservation of neurological function (qualitative survival) and prevention of neurological death (neurological survival) as 0 or 1 as described in the following: > 10 brain tumors = 0 or ≤ 10 = 1, total tumor volume > 15 cm(3) = 0 or ≤ 15 cm(3) = 1, MRI findings of localized meningeal dissemination (yes = 0 or no = 1), and neurological symptoms (yes = 0 or no = 1). According to the sum of NPSs, patients were classified into 2 subgroups: Subgroup A with a total NPS of 3 or 4 and Subgroup B with an NPS of 0, 1, or 2. The authors defined the modified BSBM according to the NPS subgroup classification applied to the original BSBM groups. The validity of this modified BSBM in 2838 consecutive patients with brain metastases treated with SRS was verified., Results: Patients included 1868 with cancer of the lung (including 1604 with non-small cell lung cancer), 355 of the gastrointestinal tract, 305 of the breast, 176 of the urogenital tract, and 134 with other cancers. Subgroup A had 2089 patients and Subgroup B 749. Median overall survival times were 2.6 months in BSBM 0 (382 patients), 5.7 in BSBM 1 (1143), 11.4 in BSBM 2 (1011) and 21.7 in BSBM 3 (302), and pairwise differences between the BSBM groups were statistically significant (all p < 0.0001). One-year qualitative survival rates were 64.6% (modified BSBM 0A, 204 patients), 45.0% (0B, 178), 82.5% (1A, 825), 63.3% (1B, 318), 86.4% (2A, 792), 73.7% (2B, 219), 91.4% (3A, 268), and 73.5% (3B, 34). One-year neurological survival rates were 82.6% (0A), 52.4% (0B), 90.5% (1A), 78.1% (1B), 91.1% (2A), 83.2% (2B), 93.9% (3A), and 76.3% (3B), where A and B identify the subgroup. Statistically significant differences in both qualitative and neurological survivals between Subgroups A and B were detected in all BSBM groups., Conclusions: The authors' new index, the modified BSBM, was found to be excellent for predicting neurological outcomes, independently of life expectancy, in SRS-treated patients with brain metastases.

The fact that accurate detection of metastatic brain tumors is important for making decisions on the treatment course of patients prompted us to develop a computer-aided diagnostic scheme for detecting metastatic brain tumors. In this paper, we first describe how we extracted the cerebral parenchyma region using a standard deviation filter. Second, initial candidates for tumors were decided by sphericity and cross-correlation value with a simulated ring template. Third, we made true positive and false positive templates obtained from actual clinical images and applied the template matching technique to them. Finally, we detected metastatic tumors using these two characteristics. Our improved method was applied to 13 cases with 97 brain metastases. Sensitivity of detection of metastatic brain tumors was 80.4%, with 5.6 false positives per patient. Our proposed method has potential for detection of metastatic brain tumors in brain magnetic resonance (MR) images.

Background: Advanced diagnostic and therapeutic developments may yield novel prognostic factors in patients with glioblastoma multiforme (GBM)., Purpose: To validate the predictive values of pretreatment quantitative diffusion-weighted (DW) magnetic resonance imaging (MRI) and MRI performed within 72 h after surgery in patients with GBM., Material and Methods: Between January 2000 and September 2009, 138 patients with GBM underwent postoperative chemoradiation therapy (chemo-RT) and longitudinal MRI before surgery, in the early postoperative period, and at 1-month intervals thereafter. The role of the patient age, Karnofsky performance scale (KPS) score, minimum apparent diffusion coefficient (ADC) on pretreatment DW-MRI, and gross residual tumor on early postoperative MRI were assessed by factor analysis of overall survival (OS). Survival curves were calculated using the Kaplan-Meier method; the multivariate Cox's proportional hazards model was used to adjust for the influence of prognostic factors. Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) criteria were used to validate the predictive value of the MRI-derived factors., Results: Substantial independent prognostic factors were the KPS score (hazard ratio [HR], 1.812), minimum ADC (HR, 2.365), and gross residual tumor (HR, 1.777). Based on MRI-derived factors, we assigned the patients to different prognostic groups in the RTOG-RPA classification and grouped them according to the level of risk, i.e. a high-risk group with low minimum ADCs (<0.93 × 10(-3) mm(2)/s) with gross residual tumor and a low-risk group with high minimum ADCs (≥0.93 × 10(-3) mm(2)/s) without gross residual tumor; the other patients were assigned to the intermediate-risk group. Median OS for the low-, intermediate-, and high-risk groups were 28.2, 14.7, and 10.8 months, respectively (P < 0.001)., Conclusion: The minimum ADC on pretreatment DW-MRI and gross residual tumor on early postoperative MRI can predict the survival in GBM patients treated with postoperative chemo-RT.

Differentiating lymphomas and glioblastomas is important for proper treatment planning. A number of works have been proposed but there are still some problems. For example, many works depend on thresholding a single feature value, which is susceptible to noise. In other cases, experienced observers are required to extract the feature values or to provide some interactions with the system. Even if experts are involved, interobserver variance becomes another problem. In addition, most of the works use only one or a few slice(s) because 3D tumor segmentation is time consuming. In this paper, we propose a tumor classification system that analyzes the luminance distribution of the whole tumor region. Typical cases are classified by the luminance range thresholding and the apparent diffusion coefficients (ADC) thresholding. Nontypical cases are classified by a support vector machine (SVM). Most of the processing elements are semiautomatic. Therefore, even novice users can use the system easily and get the same results as experts. The experiments were conducted using 40 MRI datasets. The classification accuracy of the proposed method was 91.1% without the ADC thresholding and 95.4% with the ADC thresholding. On the other hand, the baseline method, the conventional ADC thresholding, yielded only 67.5% accuracy.

Object: The authors conducted validity testing of the 5 major reported indices for radiosurgically treated brain metastases- the original Radiation Therapy Oncology Group's Recursive Partitioning Analysis (RPA), the Score Index for Radiosurgery in Brain Metastases (SIR), the Basic Score for Brain Metastases (BSBM), the Graded Prognostic Assessment (GPA), and the subclassification of RPA Class II proposed by Yamamoto-in nearly 2500 cases treated with Gamma Knife surgery (GKS), focusing on the preservation of neurological function as well as the traditional endpoint of overall survival., Methods: The authors analyzed data from 2445 cases treated with GKS by the first author (T.S.), the primary surgeon. The patient group consisted of 1716 patients treated between January 1998 and March 2008 (the Chiba series) and 729 patients treated between April 2008 and December 2011 (the Tokyo series). The interval from the date of GKS until the date of the patient's death (overall survival) and impaired activities of daily living (qualitative survival) were calculated using the Kaplan-Meier method, while the absolute risk for two adjacent classes of each grading system and both hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model., Results: For overall survival, there were highly statistically significant differences between each two adjacent patient groups characterized by class or score (all p values < 0.001), except for GPA Scores 3.5-4.0 and 3.0. The SIR showed the best statistical results for predicting preservation of neurological function. Although no other grading systems yielded statistically significant differences in qualitative survival, the BSBM and the modified RPA appeared to be better than the original RPA and GPA., Conclusions: The modified RPA subclassification, proposed by Yamamoto, is well balanced in scoring simplicity with respect to case number distribution and statistical results for overall survival. However, a new or revised grading system is necessary for predicting qualitative survival and for selecting the optimal treatment for patients with brain metastasis treated by GKS.

Background: A substantial number of patients with brain tumors develop recurrent seizures, known as tumor-associated epilepsy. It is important to identify specific subgroups of brain tumor patients with higher incidences of epilepsy because a meta-analysis failed to certify the effectiveness of prophylactic anti-epileptic drugs (AEDs) to abort tumor-associated epilepsy as a whole., Methods: To investigate the relationship between tumor location and incidence of epilepsy, we performed voxel-wise comparison between 3D MRI scans obtained from patients with meningioma-associated epilepsy and those from control patients using spatial normalization techniques on neuroimaging data. Variables such as age, tumor size, the degree of edema, and pathological diagnosis were also compared between the two groups., Results: Our results showed the highest incidence of epilepsy when the tumor was located on the premotor cortex in the frontal lobe (Z-scores >2.0, Liebermeister's quasi-exact test). The stepwise multiple regression analysis on the clinical data revealed that the tumor diameter (p < 0.001) and the patient's age (p = 0.024) were positive and negative predictors, respectively, for the onset of epilepsy., Conclusions: The incidence of epilepsy was higher in meningiomas located on the premotor cortex than on the other cortex. Larger volume also contributed to the onset of epilepsy. We suggest that variations of epilepsy incidence dependent on tumor characteristics can be considered when treating tumor-associated epilepsy.

Regression curves and local control rates of brain metastases after gamma knife treatment were evaluated to investigate differences in tumor response to radiation. A total of 203 metastases were serially evaluated using contrast-enhanced MRI (or computed tomography) at 1, 2, 3, 4.5 and 6 months after a 20-Gy dose. Differences were evaluated in regression curves and control rates between tumors ≥10 mm and tumors <10 mm in mean diameter, among three major histological subtypes of lung cancer, among adenocarcinomas of the lung, breast and colorectum, and between tumors in patients with above and below median hemoglobin levels. Smaller tumors shrank faster and yielded better control rates than larger tumors. Metastases from small cell and squamous cell carcinomas of the lung shrank faster than those from lung adenocarcinoma, but 6-month control rates were not different. Breast adenocarcinomas tended to shrink faster than lung adenocarcinomas, but the control rates were not different among adenocarcinomas of the lung, breast and colorectum. Tumors in patients with higher hemoglobin levels tended to shrink faster but the control rates were not different. Small cell and squamous cell carcinomas of the lung regress more rapidly than adenocarcinomas, although local control rates might not differ significantly., (© 2012 Japanese Cancer Association.)

Background: Brain metastases from ovarian cancer are rare, but their incidence is increasing. The purpose of this study was to investigate the characteristics of brain metastases from ovarian cancer, and to assess the efficacy of treatment with gamma knife surgery (GKS)., Methods: A retrospective review was performed of patients with brain metastases from ovarian cancer who were treated at the Tokyo Gamma Unit Center from 2006 to 2010., Results: Sixteen patients were identified. Their median age at diagnosis of brain metastases was 56.5 years, the median interval from diagnosis of ovarian cancer to brain metastases was 27.5 months, and the median number of brain metastases was 2. The median Karnofsky Performance Score (KPS) at the first GKS was 80. The median survival following diagnosis of brain metastases was 12.5 months, and 6-month and 1-year survival rates were 75 % and 50 %, respectively. The tumor control rate was 86.4 %. The KPS (<80 vs ≥80) and total volume of brain metastases (<10 cm(3) vs ≥10 cm(3)) were significantly associated with survival according to a univariate analysis (p = 0.004 and p = 0.02, respectively)., Conclusions: The results of this study suggest that GKS is an effective remedy and acceptable choice for the control of brain metastases from ovarian cancer.

Purpose: To evaluate progression pattern and progression-free interval for patients with glioblastoma multiforme (GBM), on the basis of the extent of resection., Materials and Methods: Between January 2000 and September 2009, 138 patients with GBM underwent postoperative radiation therapy and longitudinal magnetic resonance imaging studies. The operations were classified as biopsy, partial resection (PR), and gross total resection (GTR). Progression patterns were classified as gross tumor volume (GTV), T2 hyperintensity (T2h), distant, and free. We used the Kruskal-Wallis test to compare progression-free intervals on the basis of the extent of resection and the progression pattern., Results: Recurrence of biopsied and PR tumors at the GTV site was 100 and 97%, respectively. The median progression-free interval was 3 months for biopsied (n = 29), 4 months for PR (n = 70), and 8 months for GTR (n = 39) tumors (p < 0.05). The median progression-free interval for progression patterns classified as GTV (n = 97), T2h (n = 24), distant (n = 12), and free (n = 5) was 3 (p < 0.05), 7, 8, and 29 months, respectively., Conclusion: Control of the GTV can increase the progression-free interval because gross residual tumors progress earlier than infiltrating tumor cells do.

Background and Purpose: Systematic assessment of brain and head and neck tumors with 4D-CE-MRA at 3T has not been investigated. The purpose of this study was to test the hypothesis that 4D-CE-MRA at 3T can replace DSA in the identification of feeding arteries and tumor stain to plan interventional procedures in hypervascular brain and head and neck tumors., Materials and Methods: Fifteen consecutive patients with brain and head and neck tumors underwent 4D-CE-MRA at 3T and DSA. 4D-CE-MRA combined randomly segmented central k-space ordering, keyhole imaging, SENSE, and half-Fourier imaging. We obtained 30 dynamic scans every 1.9 seconds at an acquired spatial resolution of 0.9 × 0.9 × 1.5 mm; the matrix was 256 × 256. Two independent observers inspected the 4D-CE-MRA images for the main arterial feeders and tumor stain. Interobserver and intermodality agreement was assessed by κ statistics., Results: For 4D-CE-MRA, the interobserver agreement was fair with respect to the main arterial feeders and very good for the degree of tumor stain (κ = 0.28 and 0.87, respectively). Intermodality agreement was moderate for the main arterial feeders (κ = 0.45) and good for the tumor stain (κ = 0.74)., Conclusions: Although 4D-CE-MRA may be useful for evaluating tumor stain in hypervascular brain and head and neck tumors, it is not able to replace DSA in planning interventional procedures.

Background and Purpose: QUASAR is a particular application of the ASL method and facilitates the user-independent quantification of brain perfusion. The purpose of this study was to assess the intermodality agreement of TBF measurements obtained with ASL and DSC MR imaging and the inter- and intraobserver reproducibility of glioma TBF measurements acquired by ASL at 3T., Materials and Methods: Two observers independently measured TBF in 24 patients with histologically proved glioma. ASL MR imaging with QUASAR and DSC MR imaging were performed on 3T scanners. The observers placed 5 regions of interest in the solid tumor on rCBF maps derived from ASL and DSC MR images and 1 region of interest in the contralateral brain and recorded the measured values. Maximum and average sTBF values were calculated. Intermodality and intra- and interobsever agreement were determined by using 95% Bland-Altman limits of agreement and ICCs., Results: The intermodality agreement for maximum sTBF was good to excellent on DSC and ASL images; ICCs ranged from 0.718 to 0.884. The 95% limits of agreement ranged from 59.2% to 65.4% of the mean. ICCs for intra- and interobserver agreement for maximum sTBF ranged from 0.843 to 0.850 and from 0.626 to 0.665, respectively. The reproducibility of maximum sTBF measurements obtained by methods was similar., Conclusions: In the evaluation of sTBF in gliomas, ASL with QUASAR at 3T yielded measurements and reproducibility similar to those of DSC perfusion MR imaging.

Objective: It is sometimes difficult to distinguish between primary central nervous system lymphomas (PCNSL) and glioblastoma multiforme (GBM). The aim of this study was to investigate whether the addition of (18)F-2-fluoro-2-deoxy-D: -glucose positron emission tomography ([(18)F]FDG-PET) and apparent diffusion coefficients (ADC) to conventional MRI improves diagnostic accuracy for distinguishing between PCNSL and GBM with similar MRI findings., Methods: We used conventional- and diffusion-weighted MRI and FDG-PET scans of 21 patients with histologically confirmed brain tumors exhibiting similar MRI findings (PCNSL, n = 14, GBM, n = 7) in our observer performance study that consisted of 3 interpretation sessions. ADC and maximum standard uptake values (SUV(max)) of the tumors were calculated. Three radiologists first interpreted conventional MRI (1st session), then they read images to which the ADC value had been added (2nd session), and finally they interpreted images supplemented with SUV(max) (3rd session). Observer performance was evaluated using κ statistic and receiver operating characteristics analyses., Results: The addition of ADC values to conventional MRI failed to improve the differentiation between PCNSL and GBM. The addition of SUV(max) at the third session improved the diagnostic accuracy of all 3 readers and resulted in higher interobserver agreement; mean accuracy was 95% (range 93-100%). In one observer the accuracy of tumor differentiation was significantly improved at the third compared to the second session (p = 0.017)., Conclusions: In a selected group of PCNSL and GBM with similar MRI findings, the addition of quantitative FDG-PET to MRI may improve their differentiation. ADC measurement did not allow further discrimination.

We explored the feasibility of using carbon-13 ((13)C) magnetic resonance imaging ((13)C-MRI) to depict (13)C-labeled methionine-enriched gliomas at 4.7 tesla. We transplanted 2 types of glioma cells separately to 2 subcutaneous tissue sites on the backs of mice weighing 15 to 20 g. After confirming tumor growth, we used (13)C-MRI and (1)H-MRI to scan 4 mice that had been administered (13)C-labeled methionine and 2 control mice. (13)C-MRI of all 4 transplanted mice administered with (13)C-labeled methionine revealed 2 areas of hyperintensity that corresponded to the tumor sites on (1)H-MR images, but no such areas were visualized in transplanted controls. Our data suggest that (13)C-MRI can show the accumulation of (13)C-labeled tracer by gliomas.

Object: The authors retrospectively reviewed the results of Gamma Knife surgery (GKS) used as the sole treatment for brain metastases in patients who met the eligibility criteria for the ongoing JLGK0901 multi-institutional prospective trial. They also discuss the anticipated results of the JLGK0901 study., Methods: Data from 1508 consecutive cases were analyzed. All of the patients were treated at the Gamma Knife House of Chiba Cardiovascular Center or the Mito Gamma House of Katsuta Hospital between 1998 and 2007 and met the following JLGK0901 inclusion criteria: 1) newly diagnosed brain metastases, 2) 1-10 brain lesions, 3) less than 10 cm(3) volume of the largest tumor, 4) no more than 15 cm(3) total tumor volume, 5) no findings of CSF dissemination, and 6) no impairment of activities of daily living (Karnofsky Performance Scale score < 70) due to extracranial disease. At the initial treatment, all visible lesions were irradiated with GKS without upfront whole-brain radiation therapy. Thereafter, gadolinium-enhanced MR imaging was performed every 2-3 months, and new distant lesions were appropriately retreated with GKS. Patients were divided into groups according to numbers of tumors: Group A, single lesions (565 cases); Group B, 2-4 tumors (577 cases); and Group C, 5-10 tumors (366 cases). The differences in overall survival (OS) were compared between groups., Results: The median age of the patients was 66 years (range 19-96 years). There were 963 men and 545 women. The primary tumors were in the lung in 1114 patients, gastrointestinal tract in 179, breast in 105, urinary tract in 66, and other sites in 44. The overall mean survival time was 0.78 years (0.99 years for Group A, 0.68 years for Group B, and 0.62 years for Group C). The differences between Groups A and B (p < 0.0001) and between Groups B and C (p = 0.0312) were statistically significant. Multivariate analysis revealed significant prognostic factors for OS to be sex (poor prognostic factor: male, p < 0.0001), recursive partitioning analysis class (Class I vs Class II and Class II vs III, both p < 0.0001), primary site (lung vs breast, p = 0.0047), and number of tumors (Group A vs Group B, p < 0.0001). However, no statistically difference was detected between Groups B and C (p = 0.1027, hazard ratio 1.124, 95% CI 0.999-1.265)., Conclusions: The results of this retrospective analysis revealed an upper CI of 1.265 for the hazard ratio, which was lower than the 1.3 initially set by the JLGK0901 study. The JLGK0901 study is anticipated to show noninferiority of GKS as sole treatment for patients with 5-10 brain metastases compared with those with 2-4 in terms of OS.

After stereotactic radiosurgery (SRS) for brain metastases, delayed radiation effects with mass effect may occur from several months to years later, when tumors may also recur. Aggressive salvage treatment would be beneficial for patients with recurrence, but may be contraindicated for those with dominant radiation effect. Conventional magnetic resonance (MR) imaging does not provide sufficient information to differentiate delayed radiation effects from tumor recurrence. Positron emission tomography, MR spectroscopy, and other modalities sometimes may lead to false findings of tumor recurrence. We prospectively applied perfusion MR imaging for the management strategy after SRS because it gives microvascular information about the lesions. Twenty-eight lesions were enlarged on serial MR images in 27 patients 2-35 months (median: 11.8 months) after SRS for metastatic brain tumors. Each patient underwent MR perfusion imaging within a month after appearance of the growing enhanced lesion. To calculate the relative cerebral blood volume ratio (rCBV ratio), the regions of interest were located in the enhanced areas on the contrast-enhanced T1-weighted images and compared with the corresponding contralateral normal brain tissue. They were then followed-up with scheduled MR images with gadolinium enhancement at 1 to 2-month intervals afterward. Lesions which progressively increased in size on MR images were diagnosed as recurrences; lesions which disappeared or decreased in size were diagnosed as radiation necrosis. In addition, two lesions surgically removed were diagnosed by pathological examination. Follow-up MR images revealed that 21 of 28 lesions were radiation necrosis. Five lesions were diagnosed as recurrence on MR images, and the other two lesions were revealed as recurrence by pathological examination. An rCBV ratio of greater than 2.1 provided the best sensitivity and specificity for identifying recurrent metastatic tumors, at 100 and 95.2%, respectively. Perfusion MR imaging provides useful, less invasive and in-vivo information for management of growing lesions after SRS, and rCBV may be a valuable index for this diagnostic purpose.

Although brain metastases are one of the most frequently diagnosed sequelae of systemic malignancy, their optimal management still is not well defined. In that respect, the different diagnostic and therapeutic approaches of BMs patients is an issue for serious discussions. The treatment options include surgical excision, WBRT, radiosurgery, chemotherapy, immunotherapy, etc. Nowadays, the aforementioned treatment modalities are usually combined in different treatment schemes. More than one option is used for the same patient and combining these treatment modalities gives better results than when separately use them. The value of surgical excision of progressing brain metastases treated with gamma knife surgery (GKS) is not well investigated.With the present study, we aim to investigate the value of surgical excision of symptomatic brain lesions that have been previously treated with GKS.

We evaluated the results of stereotactic radiosurgery (SRS) alone using gamma knife (GK) for selected patients with 1-10 brain metastases without prophylactic whole-brain radiation therapy (WBRT) among JLGK0901-eligible cases. Seven hundred seventy-eight consecutive cases meeting the following JLGK0901 study inclusion criteria were analyzed: (1) newly diagnosed brain metastases, (2) 1-10 brain lesions, (3) less than 10 cm(3) volume of the largest tumor, (4) less than 15 cm(3) total tumor volume, (5) no magnetic resonance (MR) findings of cerebrospinal fluid (CSF) dissemination, and (6) no impaired activity of daily living [<70 Karnofsky Performance Score (KPS)] due to extracranial disease. At initial treatment, all lesions were irradiated with SRS without upfront WBRT. Thereafter, enhanced magnetic resonance imaging (MRI) was applied every 2-3 months, and new distant lesions were appropriately retreated with SRS or WBRT. We divided patients according to tumor number: single lesion for group A (280 cases), 2 for group B (135), 3-4 for group C (148), 5-6 for group D (93), and 7-10 for group E (122). Differences among groups were compared in terms of overall, neurological, qualitative, and new-lesion-free survival (NLFS). Median age was 65 years (range 26-92 years). There were 505 men and 273 women. The primary organ was lung in 579 patients, gastrointestinal tract in 79, breast in 48, urinary tract in 34, and others/unknown in 38. Mean survival time was 0.72 years (0.83 years for 1, 0.69 years for 2, 0.69 years for 3-4, 0.59 years for 5-6, and 0.62 years for 7-10 metastases). On multivariate analysis, significant poor prognostic factors for overall survival (OS) were active systemic disease, poor (<70) initial KPS, and male gender. Neurological survival and qualitative survival at 1 year were 92.7% and 88.2%, respectively. NLFS at 6 months and 1 year were 69.8% and 43.8%, respectively. There were statistically significant differences in new lesion emergence between groups A and B and between groups B and C. SRS using GK provides excellent results in selected patients with 1-10 brain lesions, without prophylactic WBRT. This study revealed that brain lesion number has no effect on any of the four types of survivals, which is anticipated to be confirmed by the JLGK0901 study.

We propose a computerized method for semi-automated segmentation of the gross tumor volume (GTV) of a glioblastoma multiforme (GBM) on brain MR images for radiotherapy planning (RTP). Three-dimensional (3D) MR images of 28 cases with a GBM were used in this study. First, a sphere volume of interest (VOI) including the GBM was selected by clicking a part of the GBM region in the 3D image. Then, the sphere VOI was transformed to a two-dimensional (2D) image by use of a spiral-scanning technique. We employed active contour models (ACM) to delineate an optimal outline of the GBM in the transformed 2D image. After inverse transform of the optimal outline to the 3D space, a morphological filter was applied to smooth the shape of the 3D segmented region. For evaluation of our computerized method, we compared the computer output with manually segmented regions, which were obtained by a therapeutic radiologist using a manual tracking method. In evaluating our segmentation method, we employed the Jaccard similarity coefficient (JSC) and the true segmentation coefficient (TSC) in volumes between the computer output and the manually segmented region. The mean and standard deviation of JSC and TSC were 74.2+/-9.8% and 84.1+/-7.1%, respectively. Our segmentation method provided a relatively accurate outline for GBM and would be useful for radiotherapy planning.

Purpose: To assess the utility of both minimum apparent diffusion coefficients (ADCs) and ADC difference values for grading astrocytic tumors at magnetic resonance imaging., Materials and Methods: The hospital's institutional review board approved this retrospective study and waived informed consent. Fifty patients (23 male patients, 27 female patients; median age, 53 years) with newly diagnosed astrocytic tumors were evaluated. Two observers blinded to clinical information independently measured the ADCs by manually placing three to five regions of interest (40-60 mm(2)) within the solid tumor either with or without contrast material-enhanced components and calculated the average ADC. Minimum and maximum ADCs were selected, and the difference between them was recorded as the ADC difference value. These ADC values were used as the parameters for tumor grading and were compared by using the Kruskal-Wallis test and receiver operating characteristic (ROC) curve analysis., Results: According to ROC analyses for distinguishing tumor grade, minimum ADCs showed the largest areas under the ROC curve. Minimum ADCs optimally helped distinguish grade 1 from higher-grade tumors at a cutoff value of 1.47 x 10(-3) mm(2)/sec and grade 4 from lower-grade tumors at a cutoff value of 1.01 x 10(-3) mm(2)/sec (P < .001 for both). ADC difference values helped distinguish grade 2 from grade 3 tumors at a cutoff value of 0.31 x 10(-3) mm(2)/sec (P < .001). When tumors were graded by using the combined minimum ADC and ADC difference cutoff values mentioned above (the two-parameter method), the following positive predictive values were obtained: grade 1 tumors, 73% (eight of 11); grade 2 tumors, 100% (five of five); grade 3 tumors, 67% (eight of 12); and grade 4 tumors, 91% (20 of 22)., Conclusion: Using a combination of minimum ADCs and ADC difference values (the two-parameter method) facilitates the accurate grading of astrocytic tumors.

The purpose of this study was to determine whether apparent diffusion coefficient (ADC) value and T2 signal intensity (SI) in primary brain lymphomas affect their SI on diffusion-weighted images (DWI). On DWI of 16 brain lesions of 16 patients, 9 (56.2%) were hyperintense (grade-3), 4 (25%) partially hyperintense (grade-2) and 3 (18.8%) isointense (grade-1). The mean ADC value of grade-3 lesions was significantly lower than of grade-1 lesions (p=0.028). The grade-1 lesions had ADC values of more than 0.8 and contrast-to-noise ratios of less than 18 on T2-weighted images. Their ADC value and T2 signal intensity affect their SI on DWI.

Background and Purpose: Although the prognostic value of perfusion MR imaging in various gliomas has been investigated, that in high-grade astrocytomas alone has not been fully evaluated. The purpose of this study was to evaluate retrospectively whether the tumor maximum relative cerebral blood volume (rCBV) on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma., Materials and Methods: Between January 1999 and December 2002, 49 patients (30 men, 19 women; age range, 23-76 years) with supratentorial high-grade astrocytoma underwent MR imaging before the inception of treatment. The patient age, sex, symptom duration, neurologic function, mental status, Karnofsky Performance Scale, extent of surgery, histopathologic diagnosis, tumor component enhancement, and maximum rCBV were assessed to identify factors affecting survival. Kaplan-Meier survival curves, the logrank test, and the multivariate Cox proportional hazards model were used to evaluate prognostic factors., Results: The maximum rCBV was significantly higher in the 31 patients with glioblastoma multiforme than in the 18 with anaplastic astrocytoma (P < .03). The 2-year overall survival rate was 67% for 27 patients with a low (< or =2.3) and 9% for 22 patients with a high (>2.3) maximum rCBV value (P < .001). Independent important prognostic factors were the histologic diagnosis (hazard ratio = 9.707; 95% confidence interval (CI), 3.163-29.788), maximum rCBV (4.739; 95% CI, 1.950-11.518), extent of surgery (2.692; 95% CI, 1.196-6.061), and sex (2.632; 95% CI, 1.153-6.010)., Conclusion: The maximum rCBV at pretreatment perfusion MR imaging is a useful clinical prognostic biomarker for survival in patients with high-grade astrocytoma.

Introduction: Although radiation therapy plays an important role in the management of children with brain tumors, radiation-induced brain damage sometimes occurs after radiation therapy. In some pediatric patients who had undergone cranial radiation therapy, we noticed cystic changes in the brain on follow-up MRI. The purpose of this study was to determine the frequency, latency, relationship with patient age, radiation dose, and serial change in the cystic changes in children after cranial irradiation., Methods: We retrospectively studied MRI in 33 children who had undergone cranial irradiation for their primary brain tumors. Postirradiation cystic change in the brain on follow-up MRI was defined as a well-demarcated, oval-shaped, CSF-like signal intensity area, and no contrast enhancement., Results: Of the 33 patients, 6 (18.2%) had one or more cystic lesions. The latency of the cystic changes ranged from 1.5 to 7 years (mean 2.6 years). Cystic changes were found in the subcortical, periventricular and other deep white matter and the basal ganglia. The size of the lesions ranged from 1 to 10 mm at their first appearance; eight cystic lesions increased in size. None the cystic lesions reduced in size or resolved with time and none required intervention. All patients with cystic changes had received irradiation when they were 6 years of age or younger. The cystic changes occurred within the radiation field in patients treated with a radiation dose of 36 Gy or more., Conclusion: Asymptomatic brain parenchymal cystic changes appear to occur in children who have undergone cranial irradiation at 6 years of age or younger.

Background and Purpose: On diffusion-weighted imaging (DWI), metastatic tumors of the brain may exhibit different signal intensities (SI) depending on their histology and cellularity. The purpose of our study was to verify the hypotheses (1) that SI on DWI predict the histology of metastases and (2) that apparent diffusion coefficient (ADC) values reflect tumor cellularity., Materials and Methods: We assessed conventional MR images, DWI, and ADC maps of 26 metastatic brain lesions from 26 patients, 13 of whom underwent surgery after the MR examination. Two radiologists performed qualitative assessment by consensus of the SI on DWI in areas corresponding to their enhancing portions. We measured the contrast-to-noise ratio (CNR) on T2-weighted images and normalized ADC (nADC) values, and compared them with tumor cellularity., Results: The mean SI on DWI and the CNR on T2-weighted images were significantly lower in well differentiated than in poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. The mean nADC value was significantly higher in well differentiated than poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. All 3 small-cell carcinomas and 1 large-cell neuroendocrine carcinoma exhibited high SI on DWI. The nADC value showed a significant inverse correlation with tumor cellularity. There was no significant correlation between the CNR and tumor cellularity., Conclusion: The SI on DWI may predict the histology of metastases; well differentiated adenocarcinomas tended to be hypointense, and small- and large-cell neuroendocrine carcinomas showed hyperintensity. Their ADC values reflect tumor cellularity.

Background and Purpose: Differentiation between tumor recurrence and treatment-related brain injury is often difficult with conventional MRI. We hypothesized that the diffusion-weighted imaging (DWI) could help differentiate these 2 conditions, because water diffusion may be greater for necrotic tissues in the treatment-related brain injury than for tumor tissues in recurrence. Our aim was to analyze whether DWI findings of recurrent tumor are distinct from those of radiation necrosis., Methods: Seventeen patients were examined prospectively. Two readers assessed the images by consensus for homogeneity and signal intensity of the lesions. Five regions of interest were drawn within the lesions on trace DWI images and apparent diffusion coefficient (ADC) maps. The minimal, maximal, and mean values of each lesion were compared between the 2 groups. Findings in 12 of 17 patients were verified histologically by surgery or biopsy; the diagnoses in the remaining 5 patients were made on the basis of follow-up MRI findings and clinical follow-up., Results: There were a total of 20 lesions; 12 lesions were due to radiation necrosis and 8 lesions to tumor recurrence. In the radiation necrosis group, 8 lesions had marked hypointensity. In the recurrence group, however, no marked hypointensity was seen. The maximal ADC values within each lesion were significantly smaller for the recurrence group than for the necrosis group (P = .039)., Conclusion: Radiation necrosis usually showed heterogeneity on DWI images and often included spotty, marked hypointensity. Significant difference was found in the maximal ADC values between radiation necrosis and tumor recurrence. DWI was useful in differentiating recurrent neoplasm from radiation necrosis.

We report the utility of a combined angiography and computed tomography (angio-CT) system in assessing drug distribution to the tumor during intra-arterial chemotherapy for metastatic brain tumors in a 65-year-old man. Although digital subtraction angiography did not clearly show tumor perfusion in two cerebellar tumors, angio-CT provided definite tumor perfusion in the complicated vascular territory, and anticancer agents were infused based on its findings. To our knowledge, however, this application for intra-arterial chemotherapy of brain tumors has not been previously described.

Objective: To assess the usefulness of a postcontrast 3-D Fourier transform (3DFT) gradient-echo (GRE) technique in dural sinus invasion and extension of extraaxial intracranial tumors in comparison with a conventional spin-echo (SE) technique., Material and Methods: Fourteen consecutive patients with 15 extra-axial tumors in contiguity with the dural sinus, including 14 meningiomas and 1 adenoid cystic carcinoma, underwent postcontrast T1-weighted SE and GRE MR studies. Detectability of dural sinus invasion and extension was evaluated using two sequences by two neuroradiologists in a blinded manner and compared with surgical results. Quantitative analysis was also performed to calculate the contrast-to-noise ratio (CNR) between lesion and dural sinus on SE and GRE images. The data were analyzed statistically using a matched paired t-test., Results: In the qualitative evaluation, the detectability of dural sinus invasion in 3DFT-GRE images was superior to that using SE images. The mean CNR for all lesions was 3.86 on SE images and 5.63 on 3DFT-GRE images (p = 0.03)., Conclusion: For evaluation of dural sinus invasion and the extension of extra-axial tumors, postcontrast 3DFT-GRE MR images were superior to conventional SE images.

Purpose: To compare qualitatively and quantitatively the contrast of brain lesions detected with fluid-attenuated inversion-recovery (FLAIR) and intermediate-weighted sequences at magnetic resonance (MR) imaging., Materials and Methods: In this prospective study, 47 patients suspected of having a brain lesion underwent MR imaging with FLAIR, intermediate-weighted, and T2-weighted sequences. Qualitative assessment was performed of lesion conspicuity, detection, overall image artifact, and additional clinical information. Contrast and contrast-to-noise ratio (CNR) were calculated between lesions and the normal brain or cerebrospinal fluid (CSF)., Results: FLAIR images were equal to intermediate-weighted images for overall lesion conspicuity and detection but were associated more often with image artifacts. Lesion-to-background contrast was significantly higher on FLAIR than on intermediate-weighted images. FLAIR images failed to demonstrate multiple sclerosis (MS) plaques located in the basal ganglia and brain stem., Conclusion: Although FLAIR images provided additional information in some cases, they did not have distinct advantages over intermediate-weighted images. When cases of MS are evaluated, intermediate-weighted images are preferable to FLAIR images. Except in cases of MS, either FLAIR or intermediate-weighted sequences should be added to T2-weighted sequences at MR imaging.

Purpose: To date, there have been no systematic reports examining cerebral lymphomas with perfusion-sensitive MRI. We sought to determine the characteristics of perfusion-sensitive MRI of these tumors., Method: Five primary and three secondary cerebral lymphomas were analyzed. None of the patients had a history of AIDS. Various areas of relative cerebral blood volume (rCBV) within tumor were analyzed, and maximum CBV ratios (CBV[tumor/contralateral]) were identified for evaluation., Results: In three primary and three secondary cerebral lymphomas, maximum CBV ratios were <2.5 (mean 1.50). In others, maximum CBV ratios were markedly higher than those of the white matter (5.38 and 5.42). Mean maximum rCBV ratios of primary and secondary cerebral lymphomas were 2.93 and 1.43, respectively. There was no significant difference between the two groups., Conclusion: Cerebral lymphomas had a tendency to have low rCBV values. This information may be helpful in diagnosing these tumors.

The purpose of this study was to evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) with echo-planar imaging (EPI) technique in depicting the tumor cellularity and grading of gliomas. Twenty consecutive patients (13 men and 7 women, ranging in age from 13 to 69 years) with histologically proven gliomas were examined using a 1.5 T superconducting imager. Tumor cellularity, analyzed with National Institutes of Health Image 1.60 software on a Macintosh computer, was compared with the minimum apparent diffusion coefficient (ADC) and the signal intensity on the T2-weighted images. The relationship of the minimum ADC to the tumor grade was also evaluated. Tumor cellularity correlated well with the minimum ADC value of the gliomas (P = 0.007), but not with the signal intensity on the T2-weighted images. The minimum ADC of the high-grade gliomas was significantly higher than that of the low-grade gliomas. Diffusion-weighted MRI with EPI is a useful technique for assessing the tumor cellularity and grading of gliomas. This information is not obtained with conventional MRI and is useful for the diagnosis and characterization of gliomas.

Objective: Our purpose was to evaluate the relationships between the ratio of maximum relative cerebral blood volume (rCBV) (rCBV ratio = rCBV[tumor]/rCBV[contralateral white matter]) and histologic and angiographic vascularities of gliomas using the gradient-echo echoplanar MR imaging technique. We also evaluated the usefulness of rCBV maps for grading gliomas., Subjects and Methods: We examined 30 patients with histologically verified gliomas. Gliomas were classified as glioblastoma, anaplastic glioma with enhancement, anaplastic glioma without enhancement, and low-grade glioma. The maximum rCBV ratio of each glioma was compared with both histologic and angiographic vascularities, and the relationship between the maximum rCBV ratios and each type of glioma was established., Results: The maximum rCBV ratios of the gliomas significantly correlated with both histologic and angiographic vascularities (p < .001). Mean values and SDs of maximum rCBV ratios of each type of tumor were 7.32+/-4.39 for glioblastomas, 5.84+/-1.82 for anaplastic gliomas with enhancement, 1.53+/-0.75 for anaplastic gliomas without enhancement, and 1.26+/-0.55 for low-grade gliomas. The maximum rCBV ratios of the glioblastomas were significantly higher than those of the anaplastic gliomas without enhancement (p = .002) and the low-grade gliomas (p < .001). The maximum rCBV ratios of the anaplastic gliomas with enhancement were higher than those of the anaplastic gliomas without enhancement and the low-grade gliomas, but the differences were not statistically significant (p = .08 and p = .03, respectively)., Conclusion: The results of perfusion-sensitive MR imaging with gradient-echo echoplanar technique correlated with both histologic and angiographic vascularities.

We studied 23 patients with meningiomas and 14 with schwannomas using dynamic spin-echo (TR/TE 200/15 ms) MRI. Histologically the meningiomas were classified according to the 1993 WHO classification. Serial images were obtained every 30s for 210s after rapid injection of gadopentetate dimeglumine (0.1 mmol/kg). The contrast-enhancement ratio (CER) was divided into three patterns; a sharp rise with a peak within 60 s (A), a relatively rapid increase with a peak between 60 and 210s (B), a slow increase without a peak (C). The patterns were correlated with the histology of the tumors. The signal intensities of the tumours on T2-weighted images were also analyzed and correlated with the dynamic patterns. Meningiomas had more varied dynamic patterns than schwannomas. Almost half of the meningiomas showed pattern A, and one third pattern C. Of six meningiothelial meningiomas showed pattern A; all schwannomas and fibrous meningiomas showed pattern C. Various patterns were observed in transitional meningiomas. Of the 8 meningiomas showing pattern C, only one gave high signal on T2-weighted images, and could not be differentiated from the schwannomas. Thus, one third of meningiomas could not be differentiated from schwannomas by the dynamic contrast enhancement alone. However, when this was combined with the signal intensity on T2-weighted images, most meningiomas could be differentiated from schwannomas.

Objective: To investigate the role of dynamic MRI in the diagnosis of chordomas at the skull base., Materials and Methods: Six patients with surgically proven chordomas of the skull base were examined with spin-echo technique (repetition time/echo time 200 ms/15 ms). Serial imaging was performed every 30 s for 240 s after a rapid injection of gadopenetate dimeglumine (0.1 mmol/kg). The contrast material enhancement ratio (CER) was analyzed. The CER was obtained for each region of interest as follows (Sn - So) x 100/Smax - So, where Sn indicates signal intensity at each dynamic phase; So, signal intensity on the image obtained before administration of contrast material; and Smax, maximum signal intensity of all dynamic imaging., Results: All chordomas showed very slow but steady increase of contrast enhancement with no peak within 240 s. The CERs of six cases at 30 s are 13 to 40 (mean value +/- standard deviation: 22.8 +/- 10.2)., Conclusion: Dynamic MRI may be helpful in differentiating between chordomas and other tumors of the skull base.