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Untreated Pediatric Primitive Neuroectodermal Tumor in Vivo: Quantitation of Taurine with MR Spectroscopy¹

¹ From the Department of Radiology (A.K., A.P., N.G., M.D.N., S.B.), Division of Neurosurgery (M.D.K., J.G.M.), and Department of Neuropathology (I.G., F.H.G.), Children's Hospital Los Angeles, 4650 Sunset Blvd, MS 81, Los Angeles, CA 90027; Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, Calif (M.D.K., J.G.M.); and Rudi Schulte Research Institute, Santa Barbara, Calif (S.B.). Received May 11, 2004; revision requested July 27; revision received October 18; accepted November 26. Supported by grant 4R33CA096032-02 from the National Cancer Institute and by the Rudi Schulte Research Institute, Santa Barbara, Calif. Address correspondence to S.B. (e-mail: sbluml{at}chla.usc.edu).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To retrospectively investigate whether quantitation of taurine (Tau) concentrations with proton magnetic resonance (MR) spectroscopy in vivo improves the differentiation of primitive neuroectodermal tumors (PNET) from other common brain tumors in pediatric patients.

MATERIALS AND METHODS: The institutional review board approved this review of clinical data; it was not necessary to obtain parental consent. This study was HIPAA compliant. Single-voxel proton spectroscopy was added to the preoperative MR imaging work-up of 29 patients (12 boys and 17 girls; mean age, 6.5 years ± 3.5) with untreated brain tumors; 13 had PNETs, and 16 had other tumors. Absolute concentrations (measured in millimoles per kilogram of brain tissue) of metabolites of the proton spectrum were determined. Student t tests were used for statistical comparisons.

RESULTS: Elevated absolute Tau concentration proved to be the most significant metabolite in the differentiation of PNETs from other tumors (6.09 mmol/kg ± 2.24 vs 0.76 mmol/kg ± 0.95, P < .001). PNETs also exhibited a higher ratio of Tau relative to choline (1.21 ± 0.48 vs 0.28 ± 0.39, P < .001), a higher ratio of Tau relative to creatine (1.28 ± 0.44 vs 0.38 ± 0.67, P < .001), a reduced a ratio of N-acetyl-aspartate relative to choline (0.20 ± 0.20 vs 0.79 ± 0.56, P < .001), and an increased choline concentration (5.30 mmol/kg ± 1.64 vs 3.08 mmol/kg ± 2.53, P < .05). Tau concentrations ranged from 2.62 to 11.15 mmol/kg in individual patients with a PNET.

CONCLUSION: Single-voxel quantitative ¹H MR spectroscopy performed in patients with untreated pediatric brain tumors showed that the Tau concentration was significantly elevated in PNETs and was useful in the differentiation of PNETs from other tumors.

© RSNA, 2005

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Primitive neuroectodermal tumors (PNETs) develop from primitive or undifferentiated neuroepithelial cells from the early development of the nervous system. PNET of the posterior fossa, or medulloblastoma, is the most common brain tumor in children (1,2). On T2-weighted magnetic resonance (MR) images, signal intensity of PNETs is similar to or lower than that of the surrounding tissue. PNETs typically show homogeneous signal enhancement on T1-weighted MR images after administration of contrast material, and cystic and/or necrotic areas are observed occasionally (2). In 80% of cases, patients with PNETs develop acute hydrocephalus accompanied by severe symptoms of headache and vomiting, and they require urgent resection of the mass.

MR spectroscopy enables the noninvasive chemical analysis of normal and abnormal tissue in vivo. Proton, or hydrogen 1 (¹H), MR spectroscopy uses hardware that is identical to that used for standard MR imaging and is available on most 1.5-T clinical MR imaging instruments. The biochemical information provided by MR spectroscopy may be useful in differential diagnosis, prognosis determination, and therapeutic decision making. Indeed, the results of several studies showed that in many cases, ¹H MR spectroscopy could be used to differentiate cerebellar PNET, low-grade tumors, and ependymomas (3,4); however, most of the earlier studies focused on the prominent peaks of the ¹H spectrum N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), and only ratios of metabolite intensities were reported. On the other hand, in vitro studies with high-spectral-resolution MR spectroscopy of resected tissue samples demonstrated significantly increased taurine (Tau) concentrations in patients with a PNET (5,6). It was suggested that Tau concentrations may correlate with malignancy, and quantitation of the Tau concentration in vivo may be of prognostic value (7). However, the MR spectroscopic signal of Tau is complex, it partially overlaps with resonances of other neurochemicals, and the concentration of Tau in brain tissue is small. This has rendered in vivo quantitation of Tau concentration in tumors difficult. Recently, because of technical advances in MR technology, quantitation of Tau has become more feasible, and age-dependent normal changes in Tau concentration have been described (8,9). Wilke et al (10) demonstrated elevated Tau concentrations in one child with a medulloblastoma, but, to our knowledge, the importance of elevated Tau concentrations in the discrimination of PNET from other common tumors in pediatric patients has not been determined. Majos et al (11) also described elevated Tau concentrations in adults with PNETs.

In view of the these factors, the purpose of our study was to investigate retrospectively whether quantitation of Tau concentrations with in vivo proton MR spectroscopy improves the differentiation of PNETs from other common brain tumors in pediatric patients.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Patients
The ¹H MR spectra of 29 brain tumors, which were obtained in consecutive patients with newly diagnosed tumors who were admitted to the hospital between August 2001 and November 2003, were retrospectively evaluated. We included 13 patients with a PNET, five patients with astrocytoma or anaplastic astrocytoma, six patients with pilocytic astrocytoma, four patients with ependymoma, and one patient with germinoma (Table 1). All PNETs were located in the posterior fossa; thus, they were classified as medulloblastoma. Of the 16 remaining tumors, eight were located in the posterior fossa, and eight were located in various regions of the cerebrum. MR imaging and MR spectroscopic studies were obtained as part of the routine work-up before surgery. Patients aged 5 years or younger were anesthetized with 100–200 mg propofol per minute per kilogram of body weight throughout the MR examination. All tumors were resected within 3 days of the MR examination, and the specimens were analyzed independently by two neuropathologists with 42 and 20 years of experience. Consensus was reached in all cases.

Acquisition and Analysis of MR Spectra
MR imaging was performed with a 1.5-T clinical imager (Signa; GE Medical Systems, Milwaukee, Wis). Standard clinical examinations in three orthogonal planes were performed in accordance with established protocols and included precontrast T1-weighted, T2-weighted fast spin-echo, and fluid-attenuated inversion-recovery MR imaging. T1-weighted MR images were obtained in at least two planes after intravenous administration of 0.1 mmol/kg gadolinium-based contrast agent (either Magnevist, Schering, Berlin, Germany; or Omniscan, Nycomed, Oslo, Norway).

Single-voxel ¹H spectra of the tumors were acquired prior to contrast agent administration by using a point-resolved spectroscopy sequence (repetition time msec/echo time msec, 1500/35; 128 signals acquired). Total acquisition time, including imager adjustments, was approximately 5 minutes. The regions of interest were carefully selected by one investigator (S.B.) to exclude any partial volume with surrounding normal-appearing tissue, and voxel size varied from approximately 5 to 10 cm³.

The region between 0.2 and 4.0 ppm of the spectrum was processed by using LCModel, version 6 software (Stephen Provencher, Oakville, Ontario, Canada). This version of the software has additional simulated model spectra for macromolecules and lipid resonances, which improves quantitation of the metabolites (12,13). Peak areas of metabolites were compared with the unsuppressed water signal, which was used as an absolute internal concentration reference. The water signal of tissue with a water content of 80% (14), which is assumed for PNET and other tumors, corresponds to a concentration of 55 mol/L multiplied by 80%, which equals 44 mol/L. Use of the water signal as an absolute reference for quantitation eliminates several sources of error, such as differences in voxel size and total gain due to coil loading, receiver gains, and hardware changes.

Three additional steps were required to arrive at the unit of measure for metabolites (ie, millimole per kilogram of tissue) that is commonly used in biochemistry. Detailed discussions about quantitation strategies can be found in the literature (15–17). In brief, concentrations were corrected for the varying fractions of tissue and cerebrospinal fluid (or fluid of necrotic and/or cystic regions within lesions) of individual regions of interest. This correction is necessary since all metabolites, with the exception of lactate and—to some extent—glucose and possibly lipids, are intracellular and virtually absent in cerebrospinal or necrotic fluid. Then, concentrations were corrected for tissue density (1.047 kg/L) and the fraction of solid material of brain tissue.

Concentrations were not corrected for MR parameters such as T1 and T2 relaxation times, as those correction factors are unknown for individual metabolites in tumor spectra. However, because the reference unsuppressed water signal undergoes similar relaxation and saturation effects, T1 and T2 corrections are likely to be very small, as the correction factors cancel each other. Indeed, both the mean and the standard deviation of metabolite concentrations in normal gray matter measured with our method are virtually identical to those reported by Kreis (15) and Kreis et al (9), who used an equivalent quantitation method but also included corrections for T1 saturation and T2 relaxation. Absolute concentrations of Tau, Cr, Cho, NAA, myo-inositol (mI), and concentration ratios relative to Cr and Cho were analyzed.

Statistical Analysis
The findings in all patients with tumors other than PNET were pooled. Measured concentrations and concentration ratios were tabulated as mean ± standard deviation, and unpaired two-tailed Student t tests with unequal variance were used for statistical comparisons of PNETs with other tumors. Statistical power analysis was performed and showed that the power level for all tests was larger than 75% for the reported significance levels. Metabolite concentration versus the age of subjects was plotted, and linear-regression analysis was performed to determine the importance of age-dependent changes. A P value of less than .05 was considered to indicate a significant difference.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Taurine was detected in all PNET spectra as a complex signal at approximately 3.4 ppm, while there was no prominent Tau peak in the other tumors (Figs 1, 2). The mean Tau concentration was higher and significantly different in patients with a PNET than in patients with another type of tumor (6.09 mmol/kg ± 2.24 vs 0.76 mmol/kg ± 0.95, P < .001) and separated all of the patients in the "Other Tumor" group (with the exception of the patient with germinoma) from patients in the PNET group (Fig 3, Table 2). Both Tau/Cho (1.21 ± 0.48 vs 0.28 ± 0.39, P < .001) and Tau/Cr (1.28 ± 0.44 vs 0.38 ± 0.67, P < .005) concentration ratios were elevated in patients with PNET when compared with concentrations in patients with another type of tumor, but this difference was less statistically significant than the absolute concentration of Tau. A considerable variation of Tau concentration was observed in individual patients with PNET and ranged from 2.62 mmol/kg to 11.15 mmol/kg, which indicates biologic heterogeneity.

View larger version (68K): [in this window] [in a new window] [Download PPT slide]   Figure 1. MR spectra and MR images of medulloblastoma. Spectra of posterior fossa obtained in patients with PNET and high, medium-high, and low (A, C, and E, respectively) concentrations of Tau. Corresponding T2-weighted transverse fast spin-echo (3500/85; matrix, 256 x 192; two signals acquired, echo train length, 16; acquisition time, 2 minutes 48 seconds) MR images indicate the regions of interest (B, D, and F). Elevated Tau concentration is indicated by complex signal intensity at approximately 3.4 ppm in each case. The inserts show the spectrum of Tau acquired from a model solution scaled to the size of fitted Tau components of the spectra, respectively. PNET spectra also exhibited elevated lipid and lactate concentrations, depleted NAA concentration, and a prominent Cho signal. The unfiltered raw data (thin line) and the LCModel fit to the data (thick line) are shown.

View larger version (73K): [in this window] [in a new window] [Download PPT slide]   Figure 2. MR spectra and MR images of other pediatric brain tumors. Representative 1H spectra and T2-weighted transverse fast spin-echo MR images (3500/85; matrix, 256 x 192; two signals acquired; echo train length, 16; acquisition time, 2 minutes 48 seconds) of a posterior fossa pilocytic astrocytoma (A and B), a posterior fossa ependymoma (C and D), and a thalamic anaplastic astrocytoma (E and F) are shown. The pilocytic astrocytoma exhibited elevated lipid and lactate concentrations and a prominent Cho concentration, whereas mI was the most prominent peak in patients with ependymoma. A small residual NAA peak was detected in anaplastic astrocytomas, while the signal intensities of Cr, Cho, and mI concentrations were comparable. In none of these spectra did analysis with LCModel software result in detectable signal that resembled the pattern of Tau at 3.3 ppm.

View larger version (19K): [in this window] [in a new window] [Download PPT slide]   Figure 3. Graph shows Tau concentrations in patients with tumor. Tau concentrations were elevated in patients with PNET and separated PNET spectra from all but one (eg, germinoma) spectra of the other tumors. There was no correlation between Tau concentration and age of subjects with PNET or another type of tumor.

An example of the potential use of proton MR spectroscopy in the differential diagnosis of PNETs is shown in Figure 4. A posterior fossa tumor extending into the left cerebellopontine angle was detected at MR imaging; however, a definitive diagnosis could not be established with MR imaging alone. The ¹H spectrum of this tumor exhibits an increased Tau concentration and a prominent Cho peak consistent with PNET, which was confirmed with histopathologic analysis after resection of the mass.

View larger version (54K): [in this window] [in a new window] [Download PPT slide]   Figure 4. MR spectra and MR images that exemplify improved preoperative diagnosis of pediatric brain tumors. A, 1H MR spectra and, B, T2-weighted transverse fast spin-echo MR image (3500/85; matrix, 256 x 192; two signals acquired; echo train length, 16; acquisition time, 2 minutes 48 seconds) indicate the region of interest in a 13-year-old girl with a posterior fossa mass initially classified as inconclusive. Although the spectral resolution of the spectrum was compromised in this case, Tau signal was readily detectable as a shoulder of the prominent Cho peak. Thus, the 1H spectrum is consistent with that in patients with a PNET, and the diagnosis was confirmed with histopathologic analysis after resection of the mass.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

PNETs originate from primitive cells that are present in early development of the nervous system and show malignant behavior. Improved initial diagnosis and differentiation of PNETs from other tumors prior to surgery have important repercussions in therapeutic decisions and prognosis. Aggressive surgical resection has been shown to have an important benefit for treatment of medulloblastomas (20–23). Thus, surgical planning is dependent on preoperative diagnostic consideration. If a PNET is suspected, a spinal staging MR imaging examination would be indicated to check for the presence of leptomeningeal metastases (3). Beyond improving presurgical diagnoses of tumors, it has long been suggested that MR spectroscopy may also provide prognostic metabolic markers that correlate with cellular proliferation and tumor aggressiveness (24) and that MR spectroscopy may be used in the clinical care of individual patients. Clinical variables permit broad distinctions between different risk groups but have proved unreliable in assigning individualized therapy (25). A study that randomized standard risk medulloblastoma patients to receive reduced versus standard neuroaxis radiation therapy was closed early after an increased risk of relapse was detected among patients who underwent the reduced treatment (26). This indicates the need for additional markers to accurately assess disease risk and tumor aggressiveness and to individualize and optimize treatment. To investigate the role of MR spectroscopy, however, larger cohorts of patients must be enrolled and followed up over the course of many years; this was outside the scope of the present study.

The focus on quantitation of the Tau concentration in vivo in this study was motivated by several observations: (a) the detection of high Tau concentrations in tissue samples of patients with PNETs in vitro (5,6), (b) the detection of high Tau concentrations in a child with a PNET (10) and in adults with medulloblastoma (11), (c) and the reported elevated Tau concentration in the developing and less differentiated brain of newborns (9). Since PNETs develop from the cells of the early brain, it was speculated that the Tau concentration is elevated in this tumor.

The quantitation of Tau in vivo with MR imaging is challenging because of the complex signal pattern, low concentration, and partial overlap with other resonances in the spectrum, particularly scyllo-inositol and glucose. Thus, a single-voxel acquisition method was selected instead of chemical shift imaging to ensure that the quality of the tumor spectrum was not affected adversely by unavoidable compromises accompanying chemical shift imaging acquisitions from larger volumes where good homogeneity of the magnetic field and water suppression is not always achieved uniformly. Absolute quantitation of spectra acquired with a single-voxel technique is also straightforward, as the signal of tissue water—which then can be used as an internal reference—is acquired very quickly, thus keeping the total acquisition time low. In contrast to most previous MR spectroscopic studies of this patient population, MR spectroscopy with a short echo time (ie, 35 msec) was used to minimize signal decay due to T2 relaxation of less prominent metabolites such as Tau.

Concentration of Tau in medulloblastoma, which was detected in 13 patients in vivo, was determined to be consistent with the reported concentrations determined with in vitro high-spectral-resolution MR spectroscopy (5) and allowed differentiation of all but one of the other tumors from the PNETs. The tumor that exhibited a high Tau concentration was a pineal germ cell tumor. Since only one spectrum of a germ cell tumor was obtained, there is no information pertaining to the extent that these tumors and PNETs overlap in their metabolic profile. It has been reported that the Tau concentrations in the normal pineal gland (and in the pituitary gland and retina) are the highest of any organ (27), which may explain the high Tau concentrations in this particular tumor. The considerable variation of Tau concentration in individual patients cannot be attributed to the limited accuracy of the quantitation method, but it does indicate biologic heterogeneity. However, the importance of different Tau concentrations and its role in PNET detection is uncertain at this stage.

In the normal brain, Tau, which is an aminosulfonic acid, is one of the most abundant amino acids in the central nervous system. It immunolocalizes to the cerebellar molecular layer, Purkinje cell bodies, mossy fibers, Golgi axons, basket cell axon terminals, and glial processes (28–30). It is abundant in the developing cerebellum and isocortex (31), and it may be an inhibitory amino acid at the synapse (32). Higher Tau concentrations were observed in malignant astrocytoma than in low-grade astrocytoma, and there is speculation that increased Tau concentration is associated with increased malignancy (7).

The number of subjects studied was small, and we cannot exclude the possibility that an increased concentration of Tau may be found in pediatric brain tumors not included in this series. Partial volume effects with surrounding tissue may dilute the specificity of MR spectroscopy in patients with smaller brain masses. Inhomogeneities caused by hemorrhage or calcifications result in spectra with low spectral resolution, and quantitation of the weak signal of metabolites such as Tau is either compromised or impossible. Because few subjects were studied, all spectra from patients with tumors other then PNETs were pooled. This may explain some of the very large standard deviations observed for peak ratios and absolute concentrations. It is expected that when more subjects are examined for each tumor type, a considerable improvement in the specificity of in vivo MR spectroscopy will be achieved. Correction factors for T1 saturation and T2 relaxation were omitted when absolute concentrations were determined; however, these correction factors are likely to be very small, and the omissions do not affect the interpretation of data obtained in this study. The water content of individual tumors was unknown. For absolute quantitation, a water content of 80%, as determined with human postmortem material (eg, the entire cerebrum), was assumed (14). The water content of individual tumors may vary, which directly affects the reported concentration; however, the variation of the water content of different tissue types is small (14) in comparison with the reported variations of metabolite concentrations in this study, and it does not affect the validity of the reported findings.

In conclusion, single-voxel quantitative ¹H MR spectroscopy was performed in untreated pediatric brain tumors and showed that the Tau concentration was significantly elevated in PNETs and useful in their differentiation from other tumors. Different Tau concentrations in individual PNETs may indicate heterogeneity in metabolism.

	ACKNOWLEDGMENTS

 
We are grateful to MR imaging technologist Gena A. Nicholson, CRT, ARRT, for help in the examination of subjects.

	FOOTNOTES

 

Abbreviations: Cho = choline • Cr = creatine • mI = myo-inositol • NAA = N-acetylaspartate • PNET = primitive neuroectodermal tumor • Tau = taurine

Authors stated no financial relationship to disclose.

Author contributions: Guarantor of integrity of entire study, S.B.; study concepts, A.K., S.B., M.D.K.; study design, A.P., S.B., F.H.G., M.D.N., M.D.K., I.G.; literature research, A.K., S.B., M.D.K.; clinical studies, A.K., N.G.; data acquisition, I.G., F.H.G., N.G., S.B., A.P.; data analysis/interpretation, I.G., F.H.G., A.K., S.B., J.G.M., M.D.N., N.G.; statistical analysis, S.B., N.G.; manuscript preparation, A.K., S.B., M.D.K., F.H.G., J.G.M., N.G.; manuscript definition of intellectual content, A.K., A.P., S.B., M.D.K.; manuscript editing, A.K., S.B.; manuscript revision/review, M.D.K., F.H.G., M.D.K., J.G.M., M.D.N., N.G.; manuscript final version approval, all authors

	References

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 

1. Childhood Brain Tumor Consortium. A study of childhood brain tumors based on surgical biopsies from ten North American institutions: sample description. J Neurooncol 1988; 6:9-23.[CrossRef][Medline]
2. Packer RJ. Childhood medulloblastoma: progress and future challenges. Brain Dev 1999; 21(2):75–81.[CrossRef][Medline]
3. Wang Z, Sutton LN, Cnaan A, et al. Proton MR spectroscopy of pediatric cerebellar tumors. AJNR Am J Neuroradiol 1995; 16(9):1821–1833.[Abstract]
4. Sutton LN, Wang Z, Gusnard D, et al. Proton magnetic resonance spectroscopy of pediatric brain tumors. Neurosurgery 1992; 31(2):195–202.[Medline]
5. Sutton LN, Wehrli SL, Gennarelli L, et al. High-resolution 1H-magnetic resonance spectroscopy of pediatric posterior fossa tumors in vitro. J Neurosurg 1994; 81(3):443–448.[Medline]
6. Kinoshita Y, Yokota A. Absolute concentrations of metabolites in human brain tumors using in vitro proton magnetic resonance spectroscopy. NMR Biomed 1997;10:2–12.[CrossRef][Medline]
7. Peeling J, Sutherland G. High-resolution 1H NMR spectroscopy studies of extracts of human cerebral neoplasms. Magn Reson Med 1992;24:123–136.[Medline]
8. Pouwels PJ, Brockmann K, Kruse B, et al. Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS. Pediatr Res 1999; 46(4):474–485.[Medline]
9. Kreis R, Hofmann L, Kuhlmann B, Boesch C, Bossi E, Hueppi PS. Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 2002;48:949–958.[CrossRef][Medline]
10. Wilke M, Eidenschink A, Muller-Weihrich S, Auer DP. MR diffusion imaging and 1H spectroscopy in a child with medulloblastoma: a case report. Acta Radiol 2001; 42(1):39–42.[Medline]
11. Majos C, Alonso J, Aguilera C, et al. Adult primitive neuroectodermal tumor: proton MR spectroscopic findings with possible application for differential diagnosis. Radiology 2002; 225(2):556–566.[Abstract/Free Full Text]
12. Seeger U, Klose U, Mader I, Grodd W, Nagele T. Parameterized evaluation of macromolecules and lipids in proton MR spectroscopy of brain diseases. Magn Reson Med 2003; 49(1):19–28.[CrossRef][Medline]
13. Auer DP, Gossl C, Schirmer T, Czisch M. Improved analysis of 1H-MR spectra in the presence of mobile lipids. Magn Reson Med 2001; 46(3):615–618.[CrossRef][Medline]
14. Lentner C, ed. Geigy scientific tables. Vol 1. Basel, Switzerland: Ciba-Geigy, 1981.
15. Kreis R. Quantitative localized 1H MR spectroscopy for clinical use. Prog NMR Spectrosc 1997;31:155–195.
16. Kreis R, Ernst T, Ross BD. Absolute quantitation of water and metabolites in the human brain. II. Metabolite concentrations. J Magn Reson 1993;102:9–19.
17. Ernst T, Kreis R, Ross BD. Absolute quantitation of water and metabolites in the human brain. I. Compartments and water. J Magn Reson 1993;102:1–8.
18. Tzika AA, Vigneron DB, Dunn RS, Nelson SJ, Ball WS Jr. Intracranial tumors in children: small single-voxel proton MR spectroscopy using short- and long-echo sequences. Neuroradiology 1996;38:254–263.[Medline]
19. Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 1993; 30(6):672–679.[Medline]
20. Evans AE, Jenkin RD, Sposto R, et al. The treatment of medulloblastoma: results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. J Neurosurg 1990; 72(4):572–582.[Medline]
21. Tait DM, Thornton-Jones H, Bloom HJ, Lemerle J, Morris-Jones P. Adjuvant chemotherapy for medulloblastoma: the first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I). Eur J Cancer 1990; 26(4):464–469.
22. Gajjar A, Sanford RA, Bhargava R, et al. Medulloblastoma with brain stem involvement: the impact of gross total resection on outcome. Pediatr Neurosurg 1996; 25(4):182–187.[Medline]
23. Zeltzer PM, Boyett JM, Finlay JL, et al. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol 1999; 17(3):832–845.[Abstract/Free Full Text]
24. Negendank WG, Sauter R, Brown TR, et al. Proton magnetic resonance spectroscopy in patients with glial tumors: a multicenter study. J Neurosurg 1996;84:449–458.[Medline]
25. Gilbertson R, Wickramasinghe C, Hernan R, et al. Clinical and molecular stratification of disease risk in medulloblastoma. Br J Cancer 2001; 85(5):705–712.[CrossRef][Medline]
26. Thomas PR, Deutsch M, Kepner JL, et al. Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation. J Clin Oncol 2000; 18(16):3004–3011.[Abstract/Free Full Text]
27. Crabai F, Sitzia A, Pepeu G. Taurine concentration in the neurohypophysis of different animal species. J Neurochem 1974; 23(5):1091–1092.[CrossRef][Medline]
28. Clements JR, Magnusson KR, Beitz AJ. Ultrastructural description of glutamate-, aspartate-, taurine-, and glycine-like immunoreactive terminals from five rat brain regions. J Electron Microsc Tech 1990; 15(1):49–66.[CrossRef][Medline]
29. Magnusson KR. Changes in the localization of taurine-like immunoreactivity during development and regeneration in the rat brain. Adv Exp Med Biol 1994;359:235–243.[Medline]
30. Gragera RR, Muniz E, De Esteban G, Alonso MJ, Martinez-Rodriguez R. Immunohistochemical demonstration of taurine in the rat cerebellar cortex: evidence for its location within mossy fibers and Golgi axons. J Hirnforsch 1995; 36(2):269–276.[Medline]
31. Flint AC, Liu X, Kriegstein AR. Nonsynaptic glycine receptor activation during early neocortical development. Neuron 1998; 20(1):43–53.[CrossRef][Medline]
32. Mandel P, Pasantes-Morales H. Taurine: a putative neurotransmitter. Adv Biochem Psychopharmacol 1976;15:141–151.[Medline]

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