The Role of Surveillance Magnetic Resonance Imaging (MRI) Scanning in Detecting Recurrent Brain Tumors in Asymptomatic Children

BACKGROUND: There is controversy regarding the utility of routine surveillance scanning for asymptomatic children with brain tumors. Although the role of CT or magnetic resonance imaging (MRI) scanning in this setting has been examined in several studies, none have focused on children followed exclusively by MRI. The purpose of this study was to determine how often recurrent brain tumors are detected by routine MRI surveillance in asymptomatic children. METHODS: The medical records of all children with brain tumors treated at Children's Hospital at Strong from 1990-1999 were reviewed. Recurrence was defined as an increase in size of the tumor on MRI scan. Astrocytomas and gangliogliomas were classified as low-grade tumors; high-grade astrocytomas, medulloblastomas, and ependymomas were classified as high-grade tumors. RESULTS: Of the 112 evaluable children with brain tumors during this time period, 46 (41%) suffered an MRI-documented recurrence. Of these 46 patients, 13 (28%) had low-grade tumors and 33 (72%) had high-grade tumors. Twenty-seven of the 46 recurrences (59%) occurred in asymptomatic children. Ten of the 13 children (77%) with recurrent low-grade tumors were asymptomatic compared to 17 of 33 children (52%) with recurrent high-grade tumors (p = 0.18). The median survival from time of recurrence for the symptomatic children was seven months, while the median survival from time of recurrence for the asymptomatic children has not yet been reached (p = 0.025). When the analysis was confined to children with high-grade tumors, there was no difference in median survival from the time of recurrence for symptomatic versus asymptomatic children (5 mo. versus 7 mo.) (p = 0.25). The frequency of detection of recurrences by surveillance scanning in asymptomatic children was 4.2% (one recurrence detected per 24 surveillence MRI scans). CONCLUSION: The majority of recurrent brain tumors are detected by MRI surveillence in asymptomatic children. However, asymptomatic recurrences were detected in only a small proportion of surveillance scans and had no impact on survival in children with high-grade tumors.     

Changes in Energy Metabolism Following Roentgen Irradiation of in Vivo Growing Ehrlich Ascites Tumour Cells Studied by 31P Magnetic Resonance Spectroscopy

The energy metabolism in Ehrlich ascites tumour cells following in vivo irradiation of a dose of 5.0 Gy was studied in vitro in their ascites fluid up to 48 hours using ³¹P magnetic resonance spectroscopy measuring ATP, ADP and inorganic phosphate (P_i). The results are also related to radiation induced changes in cell cycle composition. ATP was reduced by more than 50 per cent 20 to 24 hours after irradiation but normalized at 48 hours. ADP was reduced to about half the normal level 24 to 48 hours' after irradiation. When the ATP and ADP had reduced levels, the inorganic phosphate increased correspondingly. Addition of glucose to the ascites cell suspension at the time of minimum ATP level immediately raised the ATP: P, ratio. Since the glucose concentrations in blood and in ascites fluid following irradiation were also reduced, lack of glucose for energy production might have been a major contributing factor for the reduced ATP production.     

Diagnostic and prognostic value of 18F-DOPA PET and 1H-MR spectroscopy in pediatric supratentorial infiltrative gliomas: a comparative study

Background¹H-MR spectroscopy (MRS) and ¹⁸F-dihydroxyphenylalanine (DOPA) PET are noninvasive imaging techniques able to assess metabolic features of brain tumors. The aim of this study was to compare diagnostic and prognostic information gathered by ¹⁸F-DOPA PET and ¹H-MRS in children with supratentorial infiltrative gliomas or nonneoplastic brain lesions suspected to be gliomas.MethodsWe retrospectively analyzed 27 pediatric patients with supratentorial infiltrative brain lesions on conventional MRI (21 gliomas and 6 nonneoplastic lesions) who underwent ¹⁸F-DOPA PET and ¹H-MRS within 2 weeks of each other. ¹H-MRS data (choline/N-acetylaspartate, choline-to-creatine ratios, and presence of lactate) and ¹⁸F-DOPA uptake parameters (lesion-to-normal tissue and lesion-to-striatum ratios) were compared and correlated with histology, WHO tumor grade, and patient outcome.Results¹H-MRS and ¹⁸F-DOPA PET data were positively correlated. Sensitivity, specificity, and accuracy in distinguishing gliomas from nonneoplastic lesions were 95%, 83%, and 93% for ¹H-MRS and 76%, 83%, and 78% for ¹⁸F-DOPA PET, respectively. No statistically significant differences were found between the 2 techniques (P > .05). Significant differences regarding ¹⁸F-DOPA uptake and ¹H-MRS ratios were found between low-grade and high-grade gliomas (P≤.001 and P≤.04, respectively). On multivariate analysis, ¹⁸F-DOPA uptake independently correlated with progression-free survival (P≤.05) and overall survival (P = .04), whereas ¹H-MRS did not show significant association with outcome.Conclusions¹H-MRS and ¹⁸F-DOPA PET provide useful complementary information for evaluating the metabolism of pediatric brain lesions. ¹H-MRS represents the method of first choice for differentiating brain gliomas from nonneoplastic lesions.¹⁸F-DOPA uptake better discriminates low-grade from high-grade gliomas and is an independent predictor of outcome.     

Reduced phosphocholine and hyperpolarized lactate provide magnetic resonance biomarkers of PI3K/Akt/mTOR inhibition in glioblastoma

The phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is activated in more than88% of glioblastomas (GBM). New drugs targeting this pathway are currently in clinical trials. However, noninvasive assessment of treatment response remains challenging. By using magnetic resonance spectroscopy (MRS), PI3K/Akt/mTOR pathway inhibition was monitored in 3 GBM cell lines (GS-2, GBM8, and GBM6; each with a distinct pathway activating mutation) through the measurement of 2 mechanistically linked MR biomarkers: phosphocholine (PC) and hyperpolarized lactate.(31)P MRS studies showed that treatment with the PI3K inhibitor LY294002 induced significant decreases in PC to 34 %± 9% of control in GS-2 cells, 48% ± 5% in GBM8, and 45% ± 4% in GBM6. The mTOR inhibitor everolimus also induced a significant decrease in PC to 62% ± 14%, 57% ± 1%, and 58% ± 1% in GS-2, GBM8, and GBM6 cells, respectively. Using hyperpolarized (13)C MRS, we demonstrated that hyperpolarized lactate levels were significantly decreased following PI3K/Akt/mTOR pathway inhibition in all 3 cell lines to 51% ± 10%, 62% ± 3%, and 58% ± 2% of control with LY294002 and 72% ± 3%, 61% ± 2%, and 66% ± 3% of control with everolimus in GS-2, GBM8, and GBM6 cells, respectively. These effects were mediated by decreases in the activity and expression of choline kinase α and lactate dehydrogenase, which respectively control PC and lactate production downstream of HIF-1. Treatment with the DNA damaging agent temozolomide did not have an effect on either biomarker in any cell line. This study highlights the potential of PC and hyperpolarized lactate as noninvasive MR biomarkers of response to targeted inhibitors in GBM.     

磁敏感加权成像对单纯性脑出血和脑肿瘤卒中的鉴别诊断

目的 分析磁敏感加衩成像技术对单纯性脑出血和脑肿瘤卒中的鉴别诊断意义.方法 选择2011年脑出血患者77例,其中包括单纯性脑出血46例,脑肿瘤卒中31例,均进行磁共振增强和磁敏感加权成像检查.结果 46例单纯性脑出血中,31例边缘出现轻度强化,15例没有出现明显的强化;磁敏感加权成像扫描检查发现46例病变周围均没有出现明显迂曲增粗肿瘤样的血管样低信号.31例脑肿瘤卒中患者中,有19例边缘出现轻度强化,12例没有出现明显的强化;13例结节肿块型者,局部未出血部位出现迂曲增粗低信号,11例灶样出血者,在未出血的肿物部位出现迂曲增粗低信号,6例环型者,出现增粗低信号.磁敏感加权成像的确诊率为68.83％,明显高于磁共振增强的53.25％(P＜0.05).结论 磁敏感加权成像能提高单纯性脑出血和脑肿瘤卒中的鉴别诊断正确率,值得临床应用推广.     

Mechanism of action of lonidamine in the 9L brain tumor model involves inhibition of lactate efflux and intracellular acidification

Malignant gliomas have been associated with a high rate of glycolytic activity which is believed necessary to sustain cellular function and integrity. Since lonidamine (LND) is believed to reduce tumor glucose utilization by inhibition of the mitochondrially-bound glycolytic enzyme hexokinase (HK), ³¹P magnetic resonance spectroscopy (MRS) was used to noninvasively follow the effects of LND on both tumor pH and the high-energy phosphate metabolites; ATP, phosphocreatine (PCr) and inorganic phosphate (P_i) in subcutaneous rat 9L gliosarcomas. ³¹P tumor spectra acquired in 5 min intervals pre- and post LND administration of 50 and 100 mg/kg, i.p. revealed an acidotic pH shift of – 0.25 and – 0.45 pH units, respectively within 30 min post administration. The ATP/P_i ratio of 9L tumors decreased to 40% of control and P_i levels increased to 280% of control over a 3 hr period. LND exerted no effect on tumor blood flow and mean arterial blood pressure. Brain and muscle metabolite levels and pH were also unaffected by LND. In vitro measurements of cultured 9L tumor cell intra- and extracellular lactate, pentose phosphate pathway (PPP) and hexokinase (HK) activities suggest that the mode of action of LND involves inhibition of lactate efflux and intracellular acidification. The selective reduction of tumor energy metabolites and pH by LND may be exploitable for sensitizing gliomas to radiation, chemotherapy or hyperthermia.