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.     

Multivoxel 3D proton MR spectroscopy in the distinction of recurrent glioma from radiation injury

Objective To explore the usefulness of multivoxel 3D proton MR spectroscopy (¹H-MRS) in assessing the recurrent contrast-enhancing areas at the site of the previously treated gliomas. Materials and methods In 28 patients who had new contrast-enhancing lesions in the vicinity of the previously resected and irradiated high-grade glioma, 3D ¹H-MRS examinations were performed on a 3.0T MR scanner. Spectral data for N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were analyzed in all patients. Receiver operating characteristic analysis was performed, and the threshold value for tumor differentiation was determined. Diagnosis of these lesions was assigned by means of histopathology and follow-up. Results Diagnostic-quality 3D ¹H-MRS with quantifiable Cho, Cr, and NAA peaks was obtained in 92.9% of the cases. The Cho/NAA and Cho/Cr ratios were significantly higher in recurrent tumor than in radiation injury (P < 0.01), whereas the NAA/Cr ratios were lower in recurrent tumor than in radiation injury (P = 0.02). The Cho/Cr and Cho/NAA ratios were significantly higher in radiation injury than in normal-appearing white matter (P < 0.01), however, the NAA/Cr ratios were lower in radiation injury than in normal-appearing white matter (P = 0.01). Using receiver operating characteristic analysis, the resulting sensitivity, specificity and diagnostic accuracy of 3D ¹H-MRS were 94.1%, 100%, and 96.2%, respectively, based on the cut-off values of 1.71 for Cho/Cr or 1.71 for Cho/NAA or both as tumor criterion. Conclusion 3D ¹H-MRS could differentiate recurrent tumor from radiation injury in patients with recurrent contrast-enhancing lesions in the vicinity of the previously treated gliomas.     

[18F]-fluoro-ethyl-l-tyrosine PET: a valuable diagnostic tool in neuro-oncology,but not all that glitters is glioma

Background

To assess the sensitivity and specificity of [¹⁸F]-fluoro-ethyl-l-tyrosine (¹⁸F-FET) PET in brain tumors and various non-neoplastic neurologic diseases.

Methods

We retrospectively evaluated ¹⁸F-FET PET scans from 393 patients grouped into 6 disease categories according to histology (n = 299) or distinct MRI findings (n = 94) (low-grade/high-grade glial/nonglial brain tumors, inflammatory lesions, and other lesions). ¹⁸F-FET PET was visually assessed as positive or negative. Maximum lesion-to-brain ratios (LBRs) were calculated and compared with MRI contrast enhancement (CE), which was graded visually on a 3-point scale (no/moderate/intense).

Results

Sensitivity and specificity for the detection of brain tumor were 87% and 68%, respectively. Significant differences in LBRs were detected between high-grade brain tumors (LBR, 2.04 ± 0.72) and low-grade brain tumors (LBR, 1.52 ± 0.70; P < .001), as well as among inflammatory (LBR, 1.66 ± 0.33; P = .056) and other brain lesions (LBR, 1.10 ± 0.37; P < .001). Gliomas (n = 236) showed ¹⁸F-FET uptake in 80% of World Health Organization (WHO) grade I, 79% of grade II, 92% of grade III, and 100% of grade IV tumors. Low-grade oligodendrogliomas, WHO grade II, had significantly higher ¹⁸F-FET uptakes than astrocytomas grades II and III (P = .018 and P = .015, respectively). ¹⁸F-FET uptake showed a strong association with CE on MRI (P < .001) and was also positive in 52% of 157 nonglial brain tumors and nonneoplastic brain lesions.

Conclusions

¹⁸F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood–brain barrier and ¹⁸F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.     

Association of 82 Rubidium and 11C-methionine uptake in brain tumors measured by positron emission tomography

Summary Positron emission tomography (PET) studies have indicated that alteration of active transport contributes to increased net amino acid accumulation into human brain tumors. We compared the uptake of ¹¹C-methionine (MET) and the K⁺ analog ⁸²Rubidium (RUB) in 30 patients suffering from various brain tumors using PET. MET and RUB accumulated rapidly in tumor tissue and remained on average at a stable level thereafter from which normalized uptake values were calculated (tissue radioactivity over injected radioactivity × body weight (NU)). K1 (RUB) and K1, k2, 0 (MET) were also estimated using non-linear rate constant fitting in 17/30 patients. NU and K1 values were significantly correlated for MET (Spearman Rank p < 0.005) and RUB (p < 0.001). NU and K1 values for MET and RUB were higher in meningiomas compared to gliomas and were significantly correlated for the whole spectrum of tumors (p < 0.001). When meningiomas were excluded, the correlation was maintained. K3 values for MET (metabolic rate) in tumors were in the range of normal brain. No correlation between RUB and MET was found for normal brain. With increasing RUB uptake, the ratio of NU MET over NU RUB approached the value of 1.0. These results suggest that apart from active transport, also passive diffusion across the blood-brain barrier (BBB) may account for MET uptake from blood into tumor tissue. This probably limits the use of MET in the differential diagnosis of brain lesions where BBB disruption is present.     

Differential kinetics of α-[<Superscript>11</Superscript>C]methyl-<Emphasis Type="SmallCaps">l</Emphasis>-tryptophan on PET in low-grade brain tumors

Increased tryptophan metabolism via the kynurenine pathway is a major mechanism of tumor immuno-resistance. α-[¹¹C]Methyl-l-tryptophan (AMT) is a positron emission tomography (PET) tracer for tryptophan catabolism, and increased AMT uptake has been demonstrated in brain tumors. In this study we evaluated the use of AMT PET for detection of low-grade gliomas and glioneuronal tumors, and determined if kinetic parameters of AMT uptake can differentiate among tumor types. AMT PET images were obtained in 23 patients with newly diagnosed low-grade brain tumors (WHO grade II gliomas and WHO grade I dysembryoplastic neuroepithelial tumors [DNETs]). Kinetic variables, including the unidirectional uptake rate (K-complex) and volume of distribution (VD; which characterizes tracer transport), were measured using a graphical approach from tumor dynamic PET and blood-input data, and metabolic rates (k^￠₃ k^{\prime}_{3} ) were also calculated. These values as well as tumor/cortex ratios were compared across tumor types. AMT PET showed increased tumor/cortex K-complex (n = 16) and/or VD ratios (n = 15) in 21/23 patients (91%), including 11/13 tumors with no gadolinium enhancement on MRI. No increases in AMT were seen in an oligodendroglioma and a DNET. Astrocytomas and oligoastrocytomas showed higher k^￠₃ k^{\prime}_{3} tumor/cortex ratios (1.66 ± 0.46) than oligodendrogliomas (0.96 ± 0.21; P = 0.001) and DNETs (0.75 ± 0.39; P < 0.001). These results demonstrate that AMT PET identifies most low-grade gliomas and DNETs by high uptake, even if these tumors are not contrast-enhancing on MRI. Kinetic analysis of AMT uptake shows significantly higher tumor/cortex tryptophan metabolic ratios in astrocytomas and oligoastrocytomas in comparison with oligodendrogliomas and DNETs.     

PET Imaging of cerebral astrocytoma with 13N-ammonia

Summary We performed this study in order to assess the clinical potential of ¹³N-ammonia PET in patients with cerebral astrocytoma.Methods Dynamic ¹³N-ammonia PET was performed in 25 patients with suspected cerebral gliomas or recurrent cerebral astrocytomas (19 male and 6 female patients; age range 18–64 years) detected by MRI. The histopathological diagnoses were made for all cases either by biopsy or craniotomy, except for one patient with brain infarction and one patient with brain radiation necrosis confirmed by repeated MRI imaging. PET images were visually inspected, and the tumor-to-white matter count (T/W) ratios and the perfusion index (PI) of the tumors were determined.Results Six out of nine cases of low-grade gliomas were detected with ¹³N-ammonia PET, and three non-astrocytoma low-grade gliomas were not detected with ¹³N-ammonia PET. All 11 high-grade astrocytomas exhibited markedly increased uptake of ¹³N-ammonia. The five non-neoplastic lesions exhibited low uptake, low T/W ratios and low PI. The significant differences were observed between high-grade and low-grade gliomas with respect to both the T/W ratios and PI (T/W ratios: 5.92±2.27, n=11 vs. 1.66±0.61, n=9, P<0.01; PI: 5.22±1.67, n=11 vs. 1.60±0.54, n=9, P<0.01). There were the significant differences between the T/W ratios and PI in low-grade astrocytomas and that in non-neoplastic lesions (T/W ratios: 2.00±0.42, n=6 vs. 0.97±0.11, n=5, P<0.01; PI: 1.89±0.37, n=6 vs. 0.99±0.03, n=5, P<0.01).Conclusions There is a substantial uptake of ¹³N-ammonia in cerebral astrocytomas. ¹³N-ammonia PET may enable differentiation between low- and high-grade astrocytomas, and has the potential to enable differentiation between low-grade astrocytomas and non-neoplastic lesions.     

Comparative study of the value of dual tracer PET/CT in evaluating breast cancer

The present study was conducted to assess the relationship between tumor uptake and pathologic findings using dual‐tracer PET/computed tomography (CT) in patients with breast cancer. Seventy‐four patients with breast cancer (mean age 54 years) who underwent ¹¹C‐choline and 2‐[¹⁸F]fluoro‐2‐deoxy‐d ‐glucose (¹⁸F‐FDG) PET/CT prior to surgery on the same day were enrolled in the present study. Images were reviewed by a board‐certified radiologist and two nuclear medicine specialists who were unaware of any clinical information and a consensus was reached. Uptake patterns and measurements of dual tracers were compared with the pathologic findings of resected specimens as the reference standard. Mean (±SD) tumor size was 5.9 ± 3.2 cm. All primary tumors were identified on ¹⁸F‐FDG PET/CT and ¹¹C‐choline PET/CT. However, ¹⁸F‐FDG PET/CT demonstrated focal uptake of the primary tumor with (n = 38; 51%) or without (n = 36; 49%) diffuse background breast uptake. Of the pathologic findings, multiple logistic regression analysis revealed an independent association between fibrocystic change and diffuse background breast uptake (odds ratio [OR] 8.57; 95% confidence interval [CI] 2.86–25.66; P < 0.0001). Tumors with higher histologic grade, nuclear grade, structural grade, nuclear atypia, and mitosis had significantly higher maximum standardized uptake values (SUV_max) and tumor‐to‐background ratios (TBR) for both tracers. Multiple logistic regression analysis revealed that only the degree of mitosis was independently associated with a high SUV_max (OR 7.45; 95%CI 2.21–25.11; P = 0.001) and a high TBR (OR 5.41; 95%CI 1.13–25.96; P = 0.035) of ¹¹C‐choline PET/CT. In conclusion, ¹¹C‐choline may improve tumor delineation and reflect tumor aggressiveness on PET/CT in patients with breast cancer.     

Randomized Comparison of Intra-arterial Versus Intravenous Infusion of ACNU for Newly Diagnosed Patients with Glioblastoma

The purpose of the present study was to assess the ability of technetium-99m-tetrofosmin (^99mTc-TF) to predict tumor malignancy and to compare its uptake with that of thallium-201 (²⁰¹Tl), technetium-99m-hexakis-2-methoxyisobutyl isonitrile (^99mTc-MIBI) and fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) in brain tumors. ^99mTc-TF single-photon emission computed tomography (SPECT) imaging was performed in 22 patients with brain tumors and 3 healthy controls. Some of the patients underwent ²⁰¹Tl (n = 12) and ^99mTc-MIBI SPECT (n = 14) and ¹⁸F-FDG positron emission tomography (PET) (n = 12). The radioactivity ratio of tumor to contralateral normal tissue (T/N) and the ratio of tumor to contralateral white matter (T/WM) were calculated in SPECT and PET images, respectively. In healthy controls, ^99mTc-TF uptake was seen only in scalp, in the choroid plexus and pituitary gland, but not in normal cerebral parenchyma. TF T/N in low grade gliomas (2.8 ± 0.4) was significantly lower than that in high grade gliomas (22.5 ± 29.8) and malignant non-gliomas (8.3 ± 2.8) without overlap of values (p = 0.003 and p = 0.014, respectively). TF T/N was significantly correlated with MIBI T/N ( = 0.92, p = 0.001), Tl T/N ( = 0.72, p = 0.017), and FDG T/WM ( = 0.65, p = 0.031). There was an excellent agreement between TF T/N and MIBI T/N values on linear regression analysis (MIBI T/N = –0.63 + 0.97 × TF T/N). These preliminary results indicate that SPECT imaging with ^99mTc-TF may be useful for the non-invasive grading of brain tumors. They also suggest that ^99mTc-TF and ^99mTc-MIBI may accumulate in brain tumors by a similar mechanism or in relation to a similar process of tumor cell proliferation.     

Specific transport of 3‐fluoro‐l‐α‐methyl‐tyrosine by LAT1 explains its specificity to malignant tumors in imaging

3‐¹⁸F‐l ‐α‐methyl‐tyrosine ([¹⁸F]FAMT), a PET probe for tumor imaging, has advantages of high cancer‐specificity and lower physiologic background. FAMT‐PET has been proved useful in clinical studies for the prediction of prognosis, the assessment of therapy response and the differentiation of malignant tumors from inflammation and benign lesions. The tumor uptake of [¹⁸F]FAMT in PET is strongly correlated with the expression of L‐type amino acid transporter 1 (LAT1), an isoform of system L upregulated in cancers. In this study, to assess the transporter‐mediated mechanisms in FAMT uptake by tumors, we examined amino acid transporters for FAMT transport. We synthesized [¹⁴C]FAMT and measured its transport by human amino acid transporters expressed in Xenopus oocytes. The transport of FAMT was compared with that of l ‐methionine, a well‐studied amino acid PET probe. The significance of LAT1 in FAMT uptake by tumor cells was confirmed by siRNA knockdown. Among amino acid transporters, [¹⁴C]FAMT was specifically transported by LAT1, whereas l ‐[¹⁴C]methionine was taken up by most of the transporters. K_m of LAT1‐mediated [¹⁴C]FAMT transport was 72.7 μM, similar to that for endogenous substrates. Knockdown of LAT1 resulted in the marked reduction of [¹⁴C]FAMT transport in HeLa S3 cells, confirming the contribution of LAT1 in FAMT uptake by tumor cells. FAMT is highly specific to cancer‐type amino acid transporter LAT1, which explains the cancer‐specific accumulation of [¹⁸F]FAMT in PET. This, vice versa, further supports the cancer‐specific expression of LAT1. This study has established FAMT as a LAT1‐specific molecular probe to monitor the expression of a potential tumor biomarker LAT1.     

PET identifies transitional metabolic change in the spinal cord following a subthreshold dose of irradiation

Positron emission tomographic (PET) investigations were performed to obtainin vivo information on symptomless radiation-induced pathological changes in the human spinal cord. PET investigations were carried out prior to radiotherapy and during the regular follow-up in an early hypopharyngeal cancer patient (the spinal cord was irradiated with a biologically effective dose of 80 Gy₂), with [¹⁸F]fluorodeoxyglucose (FDG), [¹¹C]methionine and [¹⁵O]butanol as tracers; radiosensitivity and electroneuronographic (ENG) studies were also performed. A very low background FDG accumulation (mean standardized uptake values, i.e. SUV: 0.84) was observed in the spinal cord before the initiation of radiotherapy. An increased FDG uptake was measured 2 months after the completion of radiotherapy (mean SUV: 1.69), followed by a fall-off, as measured 7 months later (mean SUV: 1.21). By 44 months after completion of irradiation, the FDG accumulation in the irradiated segments of the spinal cord had decreased to a level very close to the initial value (mean SUV: 1.11). The simultaneous [¹⁵O]butanol uptake results demonstrated a set of perfusion changes similar to those observed in connection with the FDG accumulation. The patient exhibited an extremely low [¹¹C]methionine uptake within the irradiated and the nonirradiated spinal cord during the clinical course. She has not had any neurological symptoms, and the results of central ENG measurements before radiotherapy and 2 months following its completion proved normal. Radiobiological investigations did not reveal unequivocal signs of an increased radiosensitivity. A transitory increased spinal cord FDG uptake following radiotherapy may be related to the posttherapeutic mild inflammatory and regenerative processes. The normal [¹¹C]methionine accumulation observed is strong evidence against intensive cell proliferation. The high degree of normalization of the temporarily increased FDG uptake of the irradiated spinal cord segments by 44 months is in good agreement with the results of monkey studies, which demonstrated a nearly complete recovery from radiation-induced spinal cord injury. This work was supported in part by grants from the Hungarian Research Fund (OTKA T-032499 and T-046128), ETT 395/KO/2003, 37/2003 and the Ministry of Education „Széchenyi” (OM 1/008/2001).     

Peripheral benzodiazepine receptors and glucose metabolism in human gliomas

Peripheral benzodiazepine receptors (PBR) are increased in gliomas and augmented glucose metabolism is seen in malignant brain tumors. We investigated the relationship between PBR density (B_max) and glucose utilization rate (GUR) in 17 patients with cerebral gliomas of different grades. PBR B_max was assessed by [³H]PK-11195in vitro binding in surgical specimens and GUR was measured by Positron Emission Tomography with [¹⁸F]2-Fluorodeoxyglucose before the surgery. In untreated tumors there was a positive correlation between PBR B_max and GUR (2^r = 0.84). This correlation was not observed in patients who had been treated with radiation and/or chemotherapy prior to surgery (r² = 0.13). In addition, in untreated patients, the increase in PBR density and GUR appeared to be related to the degree of malignancy.     

High 123I-IMP Retention on SPECT Image in Primary Central Nervous System Lymphoma

The purpose of this study is to characterize the time course of N-isopropyl-p-[¹²³I]-iodoamphetamine (¹²³I-IMP) uptake of primary central nervous system lymphomas (PCNSL) comparing with those of other common brain tumors such as malignant gliomas and meningioma.Ten patients with PCNSL, 14 with malignant gliomas and 7 with meningioma underwent ¹²³I-IMP single photon emission computerized tomography (SPECT). Four (40%), 7 (70%) and 9 cases (90%) of PCNSL showed IMP index more than 1 on early (15min), delayed (6h) and extra-delayed (24h) SPECT images, respectively. In contrast with those IMP index was less than 1 on any image of both malignant gliomas and meningioma. The PCNSL cases with IMP index more than 1 could be distinguished from malignant gliomas and meningioma visually. The mean value of IMP index of PCNSL was increased time-dependently and was higher than those of the other two brain tumor groups on SPECT images of any time phases, and statistically different from those of malignant gliomas, however, not from those of meningioma. Interestingly, the retention rates of ¹²³I-IMP from early to extra-delayed image and delayed to extra-delayed image in PCNSL were significantly higher than those of both malignant gliomas and meningioma.The high ¹²³I-IMP retention on SPECT image is regarded as characteristic in PCNSL and the evaluation of this character is suggested to be more useful for diagnosis of this tumor than that of ¹²³I-IMP up-take on a single SPECT image.     

Usefulness of <Superscript>13</Superscript>N-NH<Subscript>3</Subscript> PET in the evaluation of brain lesions that are hypometabolic on <Superscript>18</Superscript>F-FDG PET

We investigated the usefulness of ¹³N-NH₃ PET in characterizing brain lesions which show hypometabolism on ¹⁸F-FDG PET. ¹³N-NH₃ PET was performed in 18 patients with brain lesions (in 14 for initial diagnosis and in 4 for detection of astrocytoma recurrence) that showed hypometabolism compared with normal brain tissue on ¹⁸F-FDG PET. The diagnoses were ten gliomas, one metastatic tumor, one dysembryoplastic neuroepithelial tumor (DNT), and six non-neoplastic lesions (including three cases of radiation necrosis, two cases of encephalitic foci, and one ischemic lesion). Diagnosis was verified by histopathological examination in 13 patients or was established by clinical follow-up and additional investigations in the remainder. Seven of 12 brain tumors (58%, sensitivity) showed increased ¹³N-NH₃ uptake despite hypometabolism on ¹⁸F-FDG PET. The three low-grade gliomas, one metastatic tumor, and one DNT showed decreased ¹³N-NH₃ uptake. The mean (±SD) uptake ratio of ¹³N-NH₃ was significantly higher than that of ¹⁸F-FDG (1.24 ± 0.57 vs. 0.67 ± 0.21, P < 0.01) in the tumors. By contrast, all six non-neoplastic lesions showed decreased ¹³N-NH₃ uptake (100% specificity). The mean (±SD) uptake ratio of ¹⁸F-FDG and ¹³N-NH₃ in the non-neoplastic lesions was 0.68 ± 0.15 and 0.70 ± 0.19, respectively, and there was no significant difference between them (P > 0.05). The mean (±SD) uptake ratio of ¹³N-NH₃ in the tumors was significantly higher than that in the non-neoplastic lesions (1.24 ± 0.53 vs. 0.70 ± 0.19, P < 0.05). The preliminary results of this study suggest that ¹³N-NH₃ PET may be helpful to detect and differentiate brain tumors which show hypometabolism on ¹⁸F-FDG PET from non-neoplastic lesions with high specificity, especially for cerebral astrocytomas, but the sensitivity is relatively limited.     

Accuracy of distinguishing between dysembryoplastic neuroepithelial tumors and other epileptogenic brain neoplasms with [11C]methionine PET

Background

Dysembryoplastic neuroepithelial tumors (DNTs) represent a prevalent cause of epileptogenic brain tumors, the natural evolution of which is much more benign than that of most gliomas. Previous studies have suggested that [¹¹C]methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumors, and hence optimize the management of patients. Here, we reassessed the diagnostic accuracy of MET-PET for the differentiation between DNT and other epileptogenic brain neoplasms in a larger population.

Methods

We conducted a retrospective study of 77 patients with focal epilepsy related to a nonrapidly progressing brain tumor on MRI who underwent MET-PET, including 52 with a definite histopathology. MET-PET data were assessed by a structured visual analysis that distinguished normal, moderately abnormal, and markedly abnormal tumor methionine uptake and by semiquantitative ratio measurements.

Results

Pathology showed 21 DNTs (40%), 10 gangliogliomas (19%), 19 low-grade gliomas (37%), and 2 high-grade gliomas (4%). MET-PET visual findings significantly differed among the various tumor types (P < .001), as confirmed by semiquantitative analyses (P < .001 for all calculated ratios), regardless of gadolinium enhancement on MRI. All gliomas and gangliogliomas were associated with moderately or markedly increased tumor methionine uptake, whereas 9/21 DNTs had normal methionine uptake. Receiver operating characteristics analysis of the semiquantitative ratios showed an optimal cutoff threshold that distinguished DNTs from other tumor types with 90% specificity and 89% sensitivity.

Conclusions

Normal MET-PET findings in patients with an epileptogenic nonrapidly progressing brain tumor are highly suggestive of DNT, whereas a markedly increased tumor methionine uptake makes this diagnosis unlikely.     

[<Superscript>11</Superscript>C]-<Emphasis Type="SmallCaps">l</Emphasis>-Methionine positron emission tomography in the management of children and young adults with brain tumors

Only a few Methyl-[¹¹C]-l-methionine (MET) positron emission tomography (PET) studies have focused on children and young adults with brain neoplasm. Due to radiation exposure, long scan acquisition time, and the need for sedation in young children MET-PET studies should be restricted to this group of patients when a decision for further therapy is not possible from routine diagnostic procedures alone, e.g., structural imaging. We investigated the diagnostic accuracy of MET-PET for the differentiation between tumorous and non-tumorous lesions in this group of patients. Forty eight MET-PET scans from 39 patients aged from 2 to 21 years (mean 15 ± 5.0 years) were analyzed. The MET tumor-uptake relative to a corresponding control region was calculated. A receiver operating characteristic (ROC) was performed to determine the MET-uptake value that best distinguishes tumorous from non-tumorous brain lesions. A differentiation between tumorous (n = 39) and non-tumorous brain lesions (n = 9) was possible at a threshold of 1.48 of relative MET-uptake with a sensitivity of 83% and a specificity of 92%, respectively. A differentiation between high grade malignant lesions (mean MET-uptake = 2.00 ± 0.46) and low grade tumors (mean MET-uptake = 1.84 ± 0.31) was not possible. There was a significant difference in MET-uptake between the histologically homogeneous subgroups of astrocytoma WHO grade II and anaplastic astrocytoma WHO grade III (P = 0.02). MET-PET might be a useful tool to differentiate tumorous from non-tumorous lesions in children and young adults when a decision for further therapy is difficult or impossible from routine structural imaging procedures alone.     

Neurocognitive functioning in pediatric craniopharyngioma: performance before treatment with proton therapy

Proton magnetic resonance spectroscopy (¹H-MRS) has shown promise in distinguishing recurrent high-grade glioma from posttreatment radiation effect (PTRE). The purpose of this study was to establish objective ¹H-MRS criteria based on metabolite peak height ratios to distinguish recurrent tumor (RT) from PTRE. A retrospective analysis of magnetic resonance imaging and ¹H-MRS data was performed. Spectral metabolites analyzed included N-acetylaspartate, choline (Cho), creatine (Cr), lactate (Lac), and lipids (Lip). Quantitative ¹H-MRS criteria to differentiate RT from PTRE were identified using 81 biopsy-matched spectral voxels. A receiver operating characteristic curve analysis was conducted for all metabolite ratio combinations with the pathology diagnosis as the classification variable. Forward discriminant analysis was used to identify ratio variables that maximized the correct classification of RT versus PTRE. Our results were applied to 205 records without biopsy-matched voxels to examine the percent agreement between our criteria and the radiologic diagnoses. Five ratios achieved an acceptable balance [area under the curve (AUC)?≥?0.700] between sensitivity and specificity for distinguishing RT from PTRE, and each ratio defined a criterion for diagnosing RT. The ratios are as follows: Cho/Cr?>?1.54 (sensitivity 66%, specificity 79%), Cr/Cho?≤?0.63 (sensitivity 65%, specificity 79%), Lac/Cho?≤?2.67 (sensitivity 85%, specificity 58%), Lac/Lip?≤?1.64 (sensitivity 54%, specificity 95%), and Lip/Lac?>?0.58 (sensitivity 56%, specificity 95%). Application of our ratio criteria in prospective studies may offer an alternative to biopsy or visual spectral pattern recognition to distinguish RT from PTRE in patients with gliomas.     

Localized proton spectroscopy of inoperable brain gliomas. Response to radiation therapy

Within vivo 1H-MRS resonances of several metabolites were simultaneously measured in cerebral gliomas and adjacent normal brain. 15 patients with inoperable brain gliomas all histologically verified were monitored with 1H-MRS and MRI before and after radiotherapy. 11 patients were evaluable. 1H-MRS technique evolved from single volume measurements to one dimensional and two dimensional 1H spectroscopic imaging. In all patients N-acetyl-aspartate signals were decreased in tumour areas compared to the normal brain hemisphere. No recovery was seen after radiotherapy. Choline signals were increased in tumour margins of high grade gliomas and more diffusely in low grade gliomas. In 5 patients the choline resonance decreased after radiotherapy, accompanied by a shrinkage of tumour diameter on MRI. Lactate signals were present in high grade and unspecified astrocytomas and absent in most low grade gliomas. In 3 patients the lactate signal disappeared after radiotherapy. These observations indicate the feasibility of 1H-MRS in monitoring metabolic responses on radiotherapy of brain gliomas.     

¹¹C-methionine uptake and intraoperative 5-aminolevulinic acid-induced fluorescence as separate index markers of cell density in glioma: a stereotactic image-histological analysis

BACKGROUND:

The extent of tumor resection is acknowledged as 1 of the prognostic factors for glioma. 5‐Aminolevulinic acid (5‐ALA)‐induced fluorescence guidance and neuronavigation integrated with ¹¹C‐methionine positron emission tomography (PET) are widely utilized under the expectation of improving the extent of resection. These 2 novel approaches are beneficial for glioma resections, and the combination of these approaches appears rational. However, biological characteristics reflecting 5‐ALA‐induced fluorescence and ¹¹C‐methionine uptake have not been clearly elucidated, and studies about the relationship between 5‐ALA‐induced fluorescence and ¹¹C‐methionine uptake have been limited. The present study aimed to clarify this issue.

METHODS:

Data from 11 consecutive patients harboring astrocytic tumors were analyzed: 2 grade II and 2 grade III, and 7 grade IV tumors were included. Thirty samples from these patients were obtained from the relative periphery of each tumor. Relationships among histology, 5‐ALA‐induced fluorescence and ¹¹C‐methionine uptake were analyzed by stereotactic sampling and image analysis.

RESULTS:

Uptake of ¹¹C‐methionine correlated with cell density (R² = 0.322, P = .0059). Cell density was higher in fluorescence‐positive areas than in negative areas (2760 ± 1080 vs 1450 ± 1380/mm², P = .0132). Although both ¹¹C‐methionine uptake and fluorescence seemed to correlate with cell density, no significant difference in ¹¹C‐methionine uptake was seen between fluorescence‐positive and ‐negative areas (P = .367). Multiple linear regression analysis revealed ¹¹C‐methionine uptake and 5‐ALA‐induced fluorescence as independent indices for tumor cell density.

CONCLUSIONS:

These results indicate that 5‐ALA fluorescence and ¹¹C‐methionine PET image are separate index markers for cytoreduction surgery of gliomas. Cancer 2011;. © 2011 American Cancer Society.     

氢质子磁共振波谱（^1H-MRS）分析对放射性脑坏死与脑肿瘤复发的鉴别作用

目的：探讨氢质子磁共振波谱分析（^1H-MRS）对放射性脑坏死和脑肿瘤复发的鉴别作用。方法：选择35例经放射治疗后,在常规MRI图像上发现原肿瘤部位或周边有新的异常强化灶的脑恶性胶质瘤、脑转移瘤患者,其中3—4级胶质瘤18例,脑转移瘤17例。多体素^1H-MRS采用PRESS序列。研究指标包括N-乙酰门冬氨酸（NAA）、胆碱（Cho）及肌酐（Cr）。结果：NAA、Cho及Cr下降或消失,NAAVCr比值与Cho／Cr比值均下降;脑肿瘤复发Cho上升,NAA明显下降。脑肿瘤复发和放射性脑坏死之间,Cho／Cr、Cho／NAA有统计学差异（P〈0．05）,NAAVCr无统计学差异（P〉0．05）。结论：^1H-MRS对脑肿瘤放射治疗后的脑坏死及脑肿瘤复发的评估和鉴别诊断有重要临床应用价值。     

123I-metaiodobenzylguanidine single-photon emission computerized tomography in brain tumors – a preliminary study

Summary This study evaluated the role of proton magnetic resonance spectroscopic imaging (¹H MRSI) in assessing the response of low-grade brain tumors to a chemotherapy-only treatment regimen. Specifically, it was of interest to assess if ¹H MRSI could detect early tumor response to therapy prior to magnetic resonance imaging (MRI) changes, and to establish which spectral markers were sensitive to regional changes within and around a heterogeneous tumor mass. A total of 14 patients with lower-grade gliomas were evaluated by multislice ¹H MRSI, MRI and clinical examination. Changes associated with chemotherapy were assessed by longitudinal comparisons of regional levels of choline (Cho), N-acetyl-L-aspartate (NAA), and lactate (Lac) relative to total creatine. These changes were, in turn, compared to changes on pre- and post-contrast MR images and to each patient’s clinical status. In enhancing tumor regions, there was a significant association between an increase in Lac/Cr during treatment and decreased progression-free survival time. At baseline, a low NAA/Cr in normal-appearing brain tissue adjacent to non-enhancing tumor was associated with decreased progression-free survival time, as was an increase in Cho/Cr during chemotherapy. An increase in Cho/Cr and Lac/Cr in normal-appearing brain regions next to non-enhancing tumor in one patient was noted 2 months before MRI showed progressive disease. These results suggest that ¹H MRSI can be a powerful adjunct to MRI in the assessment of tumor response to chemotherapy, and that Cho/Cr and Lac/Cr appear to be the most reliable markers of tumor progression and may predict response prior to MRI changes.