High amino acid uptake in a low-grade desmoplastic infantile ganglioglioma in a 14-year-old patient.

Amino acid uptake is higher in high-grade than in low-grade gliomas; this is the rationale for using radioactively labelled amino acids for the non-invasive grading of brain neoplasms. We present a 14-year-old boy with a low-grade desmoplastic infantile ganglioglioma (DIG) that exhibited marked contrast enhancement on magnetic resonance imaging (MRI), but no signs of infiltration and only minimal surrounding edema. In this benign neoplasm the relative uptake of the radioactively labelled amino acid I-123-alpha-methyl tyrosine (IMT), determined using single-photon emission computed tomography (SPECT), was 3.24; it was considerably higher than that of eleven other pretherapeutic low-grade gliomas where it ranged from 1.06 to 1.94 and also markedly above that average value of 2.37 found in 20 high-grade gliomas. This case report illustrates that results from emission tomography with radioactively labelled amino acids must be interpreted with caution, particularly when rare tumor entities are considered in view of uncommon clinical or radiological findings.

Intracranial metastasis of a spinal myxopapillary ependymoma. A case report.

A 37-year-old man exhibited a suprasellar tumor which histologically proved to be a myxopapillary ependymoma. Since these gliomas are virtually restricted to the cauda equina region, magnetic resonance imaging (MRI) was performed which revealed multiple spinal tumors. The present case seems to be the first report on spontaneous intracranial seeding of a spinal myxopapillary ependymoma.

Diagnosis of recurrent glioma with SPECT and iodine-123-alpha-methyl tyrosine.

UNLABELLED: Iodine-123-alpha-methyl tyrosine (IMT) allows the investigation of amino acid transport rate in brain neoplasms. It was the aim of this study to evaluate the potential of IMT-SPECT to diagnose the recurrence of gliomas after primary therapy. METHODS: Using a triple-headed SPECT camera, the cerebral uptake of IMT was determined in 27 patients 22 mo, on average, after surgical removal of a primary brain tumor. Eighteen patients had suffered from high-grade gliomas, and nine had suffered from low-grade tumors. Four patients were examined before and after surgical revision of a presumed tumor recurrence. A total of 31 studies were evaluated. The final diagnosis was based on prospective clinicopathological follow-up. Recurrence was diagnosed in 23 cases, with marked clinical deterioration occurring 3.1 mo, on average, after SPECT, and was confirmed by histopathology in 14 instances. Eight cases were free of recurrence, as evidenced by inconspicuous clinical follow-up, ranging from 6 mo to 17 mo after SPECT in seven cases, and by clinical course and histopathology in the remaining subject. RESULTS: Patients with recurrence had significantly higher ratios of IMT uptake in the tumor area to that in a background region than did patients without recurrence (2.27 +/- 0.59 compared to 1.47 +/- 0.29; p < 0.002). The best cutoff level of the IMT uptake ratio in the differentiation between recurrence and benign posttherapeutic lesion was 1.8. Using this study-specific discrimination threshold, the sensitivity and specificity of IMT-SPECT for detecting glioma recurrence were 18 of 23 (78%) and 8 of 8 (100%), respectively. The area under the binormal receiver operating characteristic curve, fitted to the data, was 0.90 +/- 0.06. CONCLUSION: Iodine-123-alpha-methyl tyrosine-SPECT is a promising new tool in the follow-up of patients with gliomas after primary therapy.

Iodine-123-alpha-methyl tyrosine in gliomas: correlation with cellular density and proliferative activity.

UNLABELLED: Amino acid transport rate in gliomas can be assessed using SPECT and the amino acid L-123I-alpha-methyl tyrosine (IMT). This study attempted to correlate the uptake of IMT by gliomas with the proliferative activity and cellular density of these neoplasms. METHODS: The study used 27 patients with gliomas, including 18 patients with high-grade tumors and nine patients with low-grade neoplasms. Amino acid transport rate was determined using IMT and the triple-headed SPECT camera. Proliferative activity was immunohistochemically assessed as the relative number of cells expressing the Ki-67 nuclear antigen; cellular density was evaluated using light microscopy. RESULTS: Relative IMT uptake correlated significantly with the proliferative fraction of tumor cells (r = 0.6, p < 0.001). There was no significant correlation between IMT uptake and cellular density (r = 0.25, p > 0.05). CONCLUSION: The uptake of the SPECT radiopharmaceutical IMT is related to proliferative activity rather than to the cellular density of gliomas.

Non-invasive grading of primary brain tumours: results of a comparative study between SPET with 123I-alpha-methyl tyrosine and PET with 18F-deoxyglucose.

Use of iodine-123-alpha-methyl tyrosine (123I-IMT) allows investigation of the amino acid transport rate in gliomas. It was the aim of this study to compare the value of measurement of glucose metabolism with that of measurement of 123I-IMT uptake for the non-invasive grading of brain tumours. The study population comprised 23 patients with histopathologically proven primary brain tumours; 14 had high-grade gliomas, and nine low-grade brain neoplasms. Glucose metabolism was studied using an ECAT EXACT 47 positron emission tomography (PET) camera and fluorine-18 fluorodeoxyglucose (18F-FDG); 123I-IMT uptake was measured with the triple-headed single-photon emission tomography (SPET) camera, MULTISPECT 3. 18F-FDG and 123I-IMT uptake was quantified as ratios between the uptake by the tumour and contralateral regions of reference. Glucose metabolism and amino acid uptake of the brain tumours correlated significantly (r=0.71, P <0.001). Assuming discrimination thresholds between high-grade and low-grade tumours of 0.8 for 18F-FDG uptake and 1.8 for 123I-IMT uptake, the accuracy values of 18F-FDG PET and 123I-IMT SPET for differentiating between high-grade and low-grade tumours were 21/23 (91%) and 19/23 (83%), respectively. The difference in diagnostic performance was not significant on receiver operating characteristic analysis (P >0.4). It is concluded that there is no major difference between the PET investigation of glucose metabolism and the less expensive SPET measurement of amino acid uptake in terms of their accuracy in evaluating the malignancy grade of primary brain tumours. This encourages the performance of further studies to analyse the potential impact of 123I-IMT SPET on the therapeutic management of patients with brain tumours.

Shifts of cortical d.c. potential induced by application of gamma-aminobutyric acid in rats in vivo.

Generally, increases in cortical activity go in parallel with negative shifts and decreases with positive shifts of cortical d.c. potentials. The aim of the present investigation was to test the effects of the inhibitory transmitter gamma-aminobutyric acid (GABA) and of GABA receptor agonists on cortical d.c. potentials. Concomitant changes of local pH were measured to get first insights as to the mechanisms of the evoked d.c. changes. The experiments were carried out on anesthetized and artificially ventilated rats. d.c. potentials were recorded at a cortical depth of about 1000 microm by glass microelectrodes. Extracellular pH was measured by ion-selective microelectrodes. GABA (0.1 mol/l), the GABA(A) receptor agonist muscimol (0.1 mmol/l) and the GABA(B) receptor agonist baclofen (0.1 mmol/l) were microejected by pressure pulses at a distance of 20-40 microm from the recording electrode. GABA evoked positive d.c. shifts with low pressure ejection and long application times. With increasing pressure the positive d.c. shifts were initially superimposed by negative ones. The GABA(A) receptor agonist muscimol elicited negative and the GABA(B) receptor agonist baclofen positive displacements of the d.c. potential independent of application time or pressure. The negative d.c. shifts induced by GABA and muscimol were associated with an extracellular alkalization of up to 0.1 pH units. The findings led one to assume (1) that the negative d.c. shift after GABA application was due to a neuronal depolarization and to an increase in excitation via local alkalization and (2) that the positive d.c. shift mirrored neuronal hyperpolarization.

Uptake of iodine-123-alpha-methyl tyrosine by gliomas and non-neoplastic brain lesions.

Using single-photon emission tomography (SPET), the radiopharmaceutical l-3-iodine-123-alpha-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.

Repetitive hypoxic exposure of brain slices and electrophysiological responses as an experimental model for investigation of cerebroprotective measurements.

An in vitro hippocampal (CA 1 region, guinea pig) slice technique using repeated hypoxia was employed to model electrophysiological changes (DC-potentials and evoked potentials (EP) by stimulation of Schaffer-collaterals) occurring in the hypoxic CA1 pyramidal layer. A standardized neuronal response under repeated hypoxic conditions was observed in this model, consisting of disappearance of EP and a trend towards partially reversible, but progressive synaptic failure subsequent anoxic depolarisation (AD). Slices treated with the calcium antagonist nimodipine showed a prolongation of AD latency between the first and following hypoxias. So it seems possible to simulate hypoxic lesions of the brain tissue by using this in vitro slice model.

Influence of size of regions of interest on the measurement of uptake of 123I-alpha-methyl tyrosine by brain tumours.

The aim of this study was to assess the influence of variations in the size of regions of interest (ROIs) on uptake values in brain tumours of L-3-iodine-123-alpha-methyl tyrosine (IMT). In addition, we attempted to establish the influence of size of ROIs on levels of significance assessing differences in mean IMT uptake between high-grade and low-grade tumours. Relative IMT uptake was determined in 19 patients with brain tumours using a MULTISPECT 3 triple-headed camera. Reconstructed image resolution was 14 mm at FWHM. Ten of the subjects suffered from high-grade gliomas (WHO grade III or IV) and nine from benign brain tumours, including eight patients with low-grade gliomas (WHO grade II). ROIs were defined by selecting those pixels within the tumour that exhibited uptake values above predefined threshold values. Using threshold values of 100, 95, 90, 85 and 80% of the mean, transaxial ROI size was approximately 0.1, 2.8, 4.3, 6.2 and 8.8 cm2, respectively. Over this range, mean, IMT uptake values decreased significantly from 2.4 to 1.9. High-grade tumours exhibited significantly higher IMT uptake than low-grade tumours at each of the threshold values. The corresponding levels of significance calculated using the Mann-Whitney U-test were between 0.01 and 0.02. Although IMT uptake values in brain tumours are significantly dependent on ROI size, levels of significance assessing differences in IMT uptake between high-grade and low-grade tumours are relatively insensitive to variations in this parameter.