Download Free Medical Imaging Brain Tumors in Newborns and Early Childhood: Utility of Combining MR Techniques PowerPoint Presentation

Imaging Brain Tumors in Newborns and Early Childhood: Utility of Combining MR Techniques PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on astrocytoma in childhood, which is titled "Imaging Brain Tumors in Newborns and Early Childhood: Utility of Combining MR Techniques", to know about the childhood CNS tumors and imaging techniques.

Tags : astrocytoma, childhood, Imaging, Brain Tumors, Newborns, Early Childhood, MR Techniques, CNS tumors, techniques

Published on : May 10, 2021 | Views : 1424 | Downloads : 5

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

IMAGING BRAIN TUMORS IN NEWBORNS AND EARLY CHILDHOOD: UTILITY OF COMBINING MR TECHNIQUES M. MORTILLA, M. ANTONELLO, C. CESARINI, L. TASCIOTTI, C. FONDA UNIVERSITY CHILDREN’S HOSPITAL A. MEYER FIRENZE, ITALY
Slide 2-

INTRODUCTION In the childhood CNS tumors are the leading cause of cancer-related death. In the last 20 years the advances in neuroimaging, neurosurgery, radiation therapy and chemotherapy have considerably improved the long term survival of children with brain tumors. Conventional MR images show definite details of brain tumor location, extension and morphological characteristics. Therefore MR imaging is widely used in the diagnosis and follow-up of pediatric patients with brain tumors.
Slide 3-

Since conventional MRI does not provide information about tissue chemistry and the interpretation of these images may lead to poor estimation of the extent of active tumor, non conventional techniques, such as diffusion images and proton spectroscopy, may be used contributing to more accurate diagnosis, prognostication and treatment planning. Tissue diagnosis remains the gold standard. The purpose of the study is to find a role of Diffusion-weighted Imaging (DWI) and proton Spectroscopy in characterizing intracerebral masses and finding a correlation between these techniques and histologic analysis of tumors.
Slide 4-

PATIENTS & METHODS 62 patients affected with brain tumors aged 1 month-6 years, were studied with a 1.5T MR scanner (Eclipse, Philips) operating at 27mT/m gradient strenght and 40 mT/m/ms slew rate. A quadrature head coil was used. T2w SE images, FLAIR, T1w SE pre and post Gadolinium injection and sometimes GE T2* were obtained. Proton Spectroscopy studies included single voxel studies (PRESS TE 40/135/270ms, STEAM TE 20ms) and/or CSI (PRESS TE 135/270.
Slide 5-

Spectroscopy acquisition were performed before the injection of the contrast media. Eight children were able to undergo to the MR without need of sedation despite the long duration of the exam (50-60 minutes). The other children were sedated with different modalities regarding weight, age and critical conditions: patients up to 18 months of age (if the weight was below 10Kg) were sedated with chlorale hydrate (50-100 mg/Kg), while from 18mo. to 6yrs. patients were sedated using Sevoflurane through laringeal mask or, rarely, with barbiturates i.v.
Slide 6-

Echo planar Imaging of Diffusion were obtained with sensitization along the slice select, read out and phase encoding axes (b- value of 800/1000/1200) with Echo Planar Single Shot sequences (TR 6450ms, TE 145.8ms, FA 90°, 5mm/1mm slice thickness/gap, 81x81 > 128x 128 reconstruction matrix, 1 NEX, chemical saturation at FA 180°, FAT saturation) with a total acquisition time of 32 seconds/15 slices.
Slide 7-

In all patients a set of 3 images along the long orthogonal axes of gradient sensitization were obtained and the DWI TRACE images were post-processed. Apparent Diffusion Coefficient (ADC) images along the same orthogonal axes were also obtained and synthetic ADC map was produced (ADC TRACE. ADC values are expressed as a number x 10-3mm2/sec.
Slide 8-

Multivoxel (CSI) were acquired with PRESS sequence, TR 1500ms, TE 135ms, FA 90°, thickness 1-1.5 cm, FOV 15 to 20cm. Chemical shift imaging matrix size 16x16, signal averages 1/2 with 1 slice per batch. Single voxel were acquired with PRESS sequence, TR 1500/2000ms, TE 270/135/40ms and with STEAM TE 20ms, FA 90°; acquisition volume from 20x20x20mm, signal averages 128 and reference averages 8.
Slide 9-

Most of the tumors underwent to surgery excision and the specimens were analyzed by an expertise in pathology in order to make diagnosis following the WHO classification and to determine cell counting expressed as mean value (m.v.) over an are of 0.083mm2. Some tumors were biopsied only, such as germinoma because they are highly responsive to therapy. Biopsy or surgical excision was not performed when the tumor arised from non resectable regions (hypotalamus, brainstem,..)
Slide 10-

OUR CASES Craniopharingioma 5 Low grade glioma (WHO I) 11 Glioma WHO II 2 High grade glioma 1 Pylocitic astrocytoma 10 Medulloblastoma (MB-PNET) 11 Germinoma 1 Subependimal gigantic astrocytoma 2 Ganglioblastoma 1 Ganglioglioma 1 Dysplasia 3 DNET 2 Teratoma 1 Metastasi 1 Altri 10
Slide 11-

Diffusion-weighted Imaging It has been reported that the ADC characterizes the biophysical characteristics of tissue microstructure and microdynamics and that it provides information (based on pathophysiologic characteristics) that differs from that obtained with contrast-enhancing imaging. It has been suggested that the minimum ADC value of high-grade gliomas is significantly higher than that of low-grade gliomas and that low ADC values were found in areas of increased cellularity.
Slide 12-

Others have suggested that the ADC may assist in the early detection of responses to anticancer therapy, because an increase in ADC values has been noted after treatment. DWI measures the molecular mobility of extracellular water,alterations in water mobility appear to reflect treatment-induced changes in tissue structure. Current understanding is that water diffusion increases acutely in tumor responsive to therapy. This precede changes in tumor volume.
Slide 13-

1H-MRS (proton magnetic resonance spectroscopy) 1H-MRS (Magnetic Resonance Spectroscopy) provides a qualitative and quantitative evaluation of brain chemistry In a proton spectrum at 1.5T the metabolites are spread out between 63 and 64 MHz, and near 300 MHz at 7T The resonant frequencies are expressed in part per million (ppm), and are read from right to left
Slide 14-

1H-MRS Fat and water are eliminated, because their peaks are to high and in spectrum scaling the brain metabolites would be invisible The water suppression is obtained with CHESS (Chemical Shift Selective) or IR (Inversion Recovery) techniques The peaks are separated into the individual frequencies through a Fourier Transform The magnetic field felt by the Protons in different molecules depends on electron clouds related to their different molecular position -> different chemical shift -> spread of single peaks over the ppm or hertz scale
Slide 15-

Sequences in 1H-MRS STEAM (Stimulated Echo Acquisition Mode): 90o refocusing pulse, short echo time, less signal-to-noise ratio PRESS (Point Resolved Spectroscopy): 180o refocusing pulse, short and long echo time With short echo time (TE 20-40 ms) metabolites of both short and long T2 are visualized With long echo time (TE 270 ms) only metabolites with long T2 are seen . Echo Time of 135 ms allows the separation of lactate doublet from lipids peaks with phase inversion. TE 65 ms increases sensitivity in lipid detection nulling lactate
Slide 16-

voxel MR Spectra may be acquired with a single voxel localized in region of interest (normal or pathological) with variable volume (usually of 2x2x2 cm or more). Small volume are characterized by less signal to noise ratio. Large volumes experience higher averaging and are not indicated for higher resolution data collection, but only for mean value in a defined area
Slide 17-

multivoxel MR Spectra may be acquired within a brain slice in 2D acquisition or more slices in 3D acquisition) with variable matrix and variable volume (usually of 1x1x1 cm or more) Small volume of voxels experience lower averaging than single voxel with larger volume. Chemical Shift Imaging (CSI) may create the metabolite maps with direct visualization of peak concentration Magnetic field inhomogeneity, insufficient shimming and lipids contamination frequently alter the quality of multivoxel spectra.
Slide 18-

Many metabolites may be identified in the proton magnetic resonance at 1.5 tesla, NAA, Cho, Cr, Lactate, myo-Inositol, Lipids are currently evaluated In the following slides there is a list brain peaks:
Slide 19-

List of metabolites that can be individualized by 1H-MRS N-acetyl methylgroups (NAA –N-acetylaspartate and NAAG – N-acetylaspartylglutamate) Methyl and Methylene protons of total creatine (Cr +PCr) Trimethylammonium groups –Choline containing (Cho) Myo-Inositol (mI) Glycine co-resonating with main mI peak (Gly) Glutamate & Glutamine with a and b-/g- protons (Glu/Gln) Glucose Scyllo-inositol Lactate GABA Glutathione Taurine Homo-carnosine Phospho-ethanolamine Macromolecules Lipids
Slide 20-

Resonance intensities expressed in ppm at 1.5T Lactate/lipids 1.33 NAA 2.02 Glx 2.2-2.4 Cr/PCr 3.02 Cho 3.22 mI 3.56
Slide 21-

Control 5 yrs old: CSI PRESS TE 135ms
Slide 22-

NAA(N-acetyl aspartate): free aminoacid, high CNS concentration (just less to glutamate) in adults in neural tissue, axons and dendrites in brain maturation also in oligodendrocytes type 2 and in non neuronal cells (mast cells) used as neuronal marker
Slide 23-

Cho (choline - N(CH3)3 GPC,PC) cellular membrane turnover marker High in tumors, demyelinating processes, inflammation Cr ( creatine - Cr + PCr = k), reference internal due to its stability, marker of byproducts of energy chains >ATP Lac (Lactate) expresses the anaerobic metabolism
Slide 24-

mI (myo inositol) glial pool marker. Small amounts from glycine Glu or Glx (glutamate) neurotransmitter, intermediate in aminoacid catabolism Gln (glutamine) metabolism of glutamate glial marker
Slide 25-

PRESS TE 135ms STEAM TE 20ms a b c 4 years old girl: pilocytic astrocytoma Lactate in solid nodule High choline peak In P.A. the Choline Levels are usually below 3.0, while in MB-PNET are usually higher  Cho  Lac  NAA
Slide 26-

DWI TRACE ADC TRACE Nr. of cell: 0.083mm2 215 m.v. 185 m.v. Mean ADC value 1.68 10-3 mm2 /sec 4y.o. girl: pilocytic astrocytoma. Histologic surgical specimen and cell density counting over mixoid (185 cells) and more compact (215 cells) portion of the tumor.
Slide 27-

Boy, 13 months BRAINSTEM GLIOMA Cho/Cr NAA/Cr Lac : MRS data indicates that it could be a pilocytic astrocytoma PRESS TE 135ms PRESS TE 270ms
Slide 28-

1st MRI: diagnosis (WHO I) 2nd:after chemo High Cho 3rd:6mo. after Stop Therapy Higher Cho, low NAA, high lac PRESS TE 270ms 6 years old boy: Brainstem glioma FLAIR C.E. FSE T1 ADC TRACE
Slide 29-

DWI TRACE ADC TRACE At diagnosis b = 800 DWI ADC DWI TRACE ADC TRACE After chemotherapy
Slide 30-

6 years old girl: glioma of the midbrain (WHO I) PRESS TE 40ms Mild reduction of NAA/Cr and mI/Cr
Slide 31-

Boy, 4 years old: Astrocytoma WHO II-III Important reduction of NAA/Cr and moderate increase of Cho/Cr
Slide 32-

CSI PRESS TE 270 ms VOXEL 8 STEAM TE 20 ms CSI PRESS TE 270ms: high choline peak (Cho/Cr 4.09), low NAA intensity signal. Small amount of lactate. STEAM TE 20ms: evident lipids peak. a b 6 years old boy: medulloblastoma
Slide 33-

Medulloblastoma. a Nr. of cell: 0.083mm2 750 m.v. Mean ADC value 1.2 10-3 mm2 /sec DWI TRACE ADC TRACE
Slide 34-

PRESS TE 135ms STEAM TE 20ms 6 years old girl.: PNET-MB a b .. STEAM 20: evident mI, lipids and Glx peaks PRESS TE 135ms: high choline peak (Cho/Cr 12.4) and low NAA intensity signal.
Slide 35-

PRESS TE 135ms STEAM TE 20ms PRESS 135: high choline peak (Cho/Cr 2.6), low NAA signal intensity. Presence of lactate. STEAM 20: evident lipids and mI peaks. 11 months old girl: pinealoblastoma.
Slide 36-

Pinealoblastoma DWI TRACE ADC TRACE Mean ADC value 0.4 x 10-3 mm2 /sec Nr. of cell: 0.083mm2 900 m.v.
Slide 37-

PRESS TE 135ms 6 years old girl: choroid plexus carcinoma. Mean ADC value 1.0 10-3 mm2 /sec reduced Cr All metabolites, included Creatine, but Choline are reduced Cho/Cr 31.5 neoplasm do not produce NAA
Slide 38-

5 years old girl: germinoma. high lipids signal. PRESS TE 135ms 320 m.v. Nr. of cell: 0.083mm2 Mean ADC value 0.57 10-3 mm2 /sec
Slide 39-

PRESS TE 270ms CSI PRESS TE 135ms Girl, 23 months metastasis from rabdomyosarcoma Cho/Cr 6.1 Lac/Cr 6.8 NAA/Cr
Slide 40-

STEAM TE 20ms Cortical Dysplasia TAYLOR TYPE Increased mI/Cr ratio
Slide 41-

Boy, 20 months: Tuberous sclerosis Increased mI/Cr ratio PRESS TE 40ms STEAM TE 20ms
Slide 42-

Germinoma JDGG Pinealoblastoma PNET MB-PNET Pylocitic Astrocytoma (solid portion) ADC vs.Cells number correlation more highly cellular > smaller intercellular spaces > lower ADC
Slide 43-

BRAIN ABSCESS vs. TUMOR DWI is able to discriminate between abscesses and tumors: a) brain abscess; b) supratentorial ependymoma a b DWI ADC
Slide 44-

Boy, 6 years old: brain abscess Most of the metabolites are reduced. Lipids and lactate are present
Slide 45-

Conclusions Brain tumors in children are highly heterogeneous for histology, prognosis and therapeutic response. Diagnosis and therapy of those, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures that limits biopsy. The utility of combining data from biologically important intracellular molecules, obtained with proton MR spectroscopy and from water mobility, obtained with diffusion imaging, is clearly addressed to increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors.
Slide 46-

DWI enable to better differenciate between low- grade and high-grade tumor: high-grade gliomas have lower ADC values than low-grade gliomas. ADC maps are easily generated from routine fast diffusion-weighted imaging by use of software available on many MR systems. ADC may be a more direct indicator of changes in the brain than are other physical parameters. The degree of diffusion is strongly affected by microscopic biological structures such as the number, type and spatial arrangement of cells. These structures create barriers to the free diffusion of water so changes in diffusion may more directly reflect changes occurring within and between cells.
Slide 47-

It still debating if ADC measurement can be used to determine the extent of tumor infiltration and to differentiate infiltration from peritumoral edema. It has been suggested that tumor infiltration is characterized by lower ADC values than edema. In our experience we found that quite often this is true but we always prefer to be cautious adding spectroscopy data when is possible to perform CSI. We also utilize high-b-value DWI that increase the anisotropy so is more accurate in the assessment of infiltration. Since infiltration occurs within and along white matter tracts, diffusion tensor imaging may yield more useful information.
Slide 48-

Proton MR Spectroscopy enables the measurements of multiple chemical metabolites in normal and abnormal brain parenchyma. Cho/Cr or Cho/NAA in a lesion correlate with higher cellular proliferation rate and reflect the presence of a more malignant and rapidly growing tumor. It is necessary to correlate MRI data since pilocytic astrocytoma has high Choline and lactate despite it is considered benign: usually Cho/Cr ratio is less than 3. NAA is considered a neuronal marker, which decreases with replacement of neurons by tumor (or other non-neuronal tissue, including necrosis). In choroid plexus carcinoma a very low NAA/Cr is characteristic since the tumor does not produce NAA.
Slide 49-

MRS can be used to follow tumors over time, since patients can serve as their own control after obtaining a baseline scan. CSI may be useful in monitoring the surgical scar: elevation of Cho/Cr ratio is index of a relapse. We have found this index reliable mostly in anaplastic ependymoma. It has been suggested that children with higher total creatine levels are more responsive to radiation or chemotherapy. In our experience children with low-grade gliomas that have significantly higher baseline Cho/Cr ratio have more chance to have tumor that progress over 2 years than those that have stable tumors. Lactate is no more considered an indicator of malignancy since it is found in benign tumors such as pilocytic astrocytoma.
Slide 50-

Lipids may be detected in enhancing and non enhancing tumor regions. For a reliable detection of lipid peak it would be better to use acquisition protocols with a TE 65ms that null lactate peak. Lipids represent microscopic tumor cell necrosis or membrane breakdown that may precede necrosis. Lipids may be present in viable tumor, presumably because of poor perfusion and hypoxia and they undergo major intensity changes during apoptosis. They are found also in radiation necrosis. Because glial tumors are grade according to their cellularity, proliferative activity and degree of necrosis, Cho mapping (increased cellularity and proliferative activity) may added value to MRI in childrens with brain tumors, especially when it is combined with lipid mapping (necrosis and/or apoptosis).
Slide 51-

Arnold DL, De Stefano N. Magnetic resonance spectroscopy in vivo: applications in neurological disorders. Ital J Neurol Sci 1997; 18: 321-329 Ashwal S, Holshouser B, Tong K, Serna T, Osterdock R, Gross M, Kido D. Proton spectroscopy detected myoinositol in children with traumatic brain injury. Pediatric Research 2004; 56:630-638 Astrakas LG, Zurakowski D, Tzika AA, Zarifi MK, Anthony DC, De Girolami U, Tarbell NJ, Black PM. Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors. Clin Cancer Res. 2004 Dec 15;10(24):8220-8. Barkovich AJ, Good WV, Koch TK, et al. Mitochondrial disorders: analysis of their linical and imaging characteristics. AJNR 1993; 14: 1119-1137 Bottomley PA. Spatial localization in NMR spectroscopy in vivo. Ann NY Acad Sci 1987; 508: 333–348 Bottomley PA. Spatial localization in NMR spectroscopy in vivo. Ann NY Acad Sci 1987; 508: 333-348 Brooks WM, Friedman SD, Gasparovic C. Magnetic resonance spectroscopy in traumatic brain injury. J Head Trauma Rehabil 2001; 16:146–164 Castillo M, Kwock L, Scatliff J, Mukherji SK. Proton MR spectroscopy in neoplastic and non-neoplastic brain disorders. Magn Reson Imaging Clin N Am. 1998; 6(1):1-20 Cecil KM, Jones BV. Magnetic resonance spectroscopy of the pediatric brain. Top Magn Reson Imaging 2001;12:435–452 Cendes F, Andermann F, Preul MC, et al. Lateralization of temporal lobe epilepsy based on regional metabolic abnormalities in proton magnetic resonance spectroscopic imaging. Ann Neurol 1994; 35: 211-216 Frahm J, Hanefeld F. Localized proton magnetic resonance spectroscopy of cerebral metabolites. Neuropediatrics 1996; 27: 64-69 Grodd W, Krageloh-Mann I, Klose U, et al. Metabolic and destructive brain disorders n children: findings with localized proton MR spectroscopy. Radiology 1991; 81: 173-181 Howe FA, Maxwell RJ, Saunders DE, et al. Proton spectroscopy in vivo. Magn Reson Q 1993; 9: 31-59 Hunter JV, Wang ZJ. MR spectroscopy in pediatric neuroradiology. Magn Reson Imaging Clin N Am. 2001; 9(1):165-89 Hwang JH, Egnaczyk GF, Ballard E, Dunn RS, Holland SK, Ball WS Jr. Proton MR spectroscopic characteristics of pediatric pilocytic astrocytomas. AJNR Am J Neuroradiol. 1998; 19(3):535-40 Kadota T, Horinouchi T, Kuroda C. Development and aging of the cerebrum: assessment with proton MR spectroscopy. AJNR Am J Neuroradiol 2001;22:128–135 Kreis R, Ernst T, Ross BD. Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magn Reson Med; 1993 30: 424–437 Kruse B, Hanefeld F, Christen HJ, et al. Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance spectroscopy in vivo. J Neurol 1993; 241: 68-74 Selected References
Slide 52-

Leonard JC, Younkin DP, Chance B, Subramanian VH, Leigh JS Jr, Alavi A, Kressel HY, Zimmerman R, Delivoria-Papadopoulos M. Nuclear magnetic resonance: an overview of its spectroscopic and imaging applications in pediatric patients. J Pediatr. 1985; 106(5):756-61. Moore GJ. Proton magnetic resonance spectroscopy in pediatric neuroradiology. Pediatr Radiol. 1998 Nov;28(11):805-14. Norfray JF, Tomita T, Byrd SE, Ross BD, Berger PA, Miller RS. Clinical impact of MR spectroscopy when MR imaging is indeterminate for pediatric brain tumors. AJR Am J Roentgenol 1999; 173 :119 –125 Norfray JF, Tomita T, Byrd SE, Ross BD, Berger PA, Miller RS. Clinical impact of MR spectroscopy when MR imaging is indeterminate for pediatric brain tumors. AJR Am J Roentgenol. 1999; 173(1):119-25 Novotny E, Ashwal S, Shevell M. Proton magnetic resonance spectroscopy: an emerging technology in pediatric neurology research. Pediatr Res. 1998; 44(1):1-10 Penrice J, Cady EB, Lorek A, Wyelinska M, Amess P, Aldridge R, Stewart A, Wyatt J. Proton magnetic resonance spectroscopy of the brain in normal preterm and term infants and early changes after perinatal hypoxia-ischemia. Pediatr Res 1996; 40: 6–14 Pietz J, Kreis R, Schmidt H, Meyding-Lamadé UK, Rupp A, Boesch C. Phenylketonuria: findings at MR imaging and localized in vivo H-1 MR spectroscopy of the brain in patients with early treatment. Radiology 1996; 413–420 Pouwels PJ, Frahm J. Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS. Magn Reson Med 1998;39:53–60 Rand SD, Prost R, Li SJ. Proton MR spectroscopy of the brain. Neuroimaging Clin N Am. 1999; 9(2):379-9 Robertson NJ, Lewis RH, Cowan FM, Allsop JM, Counsell SJ, Edwards AD, Cox IJ. Early increases in brain myo-inositol measured by proton magnetic resonance spectroscopy in term infants with neonatal encephalopathy. Pediatr Res. 2001; 50(6):692-700. Ross BD. Biochemical considerations in 1H spectroscopy. Glutamate and glutamine: myo-inositol and related metabolites. NMR Biomed 1991; 4: 59–63 Ross BD. Biochemical considerations in 1H spectroscopy. Glutamate and glutamine; myo-inositol and related metabolites. NMR 1991; Biomed 4: 59-63 Rutherford MA, Pennock JM, Counsell SJ, Mercuri E, Cowan FM, Dubowitz LMS, Edwards AD. Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy. Pediatrics 1998; 102: 323–328 Saunders DE, Howe FA, van den Boogaart A, Griffiths JR, Brown MM. Discrimination of metabolite from lipid and macromolecule resonances in cerebral infarction in humans using short echo proton spectroscopy. J Magn Reson Imaging 1997 ; 7: 1116–1121 Thompson JE, Castillo M, Kwock L. MR spectroscopy in the evaluation of epilepsy. Magn Reson Imaging Clin N Am. 1998; 6(1):21-9. Tzika A, Astrakas L, Kieran M, Zurakowski D, Zarifi M, Poussaint T Choline to n-acetylaspartate ratio is predictive of pediatric brain tumor progression. Radiology 2001; 221(Suppl):488 Tzika AA, Ball WS Jr, Vigneron DB, et al.Childhood adrenoleukodystrophy: assessment with proton MR spectroscopy. Radiology 1993; 189: 467-480 Tzika AA, Zarifi MK, Goumnerova L, Astrakas LG, Zurakowski D, Young-Poussaint T, Anthony DC, Scott RM, Black PM. Neuroimaging in pediatric brain tumors: Gd-DTPA-enhanced, hemodynamic, and diffusion MR imaging compared with MR spectroscopic imaging. AJNR Am J Neuroradiol. 2002;23(2):322-33 Warren KE. NMR spectroscopy and pediatric brain tumors. Oncologist 2004; 9(3):312-8. Zimmerman RA, Wang ZJ. The value of proton MR spectroscopy in pediatric metabolic brain disease. AJNR 1997; 18: 1872-1879