|Year : 2016 | Volume
| Issue : 1 | Page : 136-140
The role of proton magnetic resonance spectroscopy in grading of brain gliomas
Hala Hafez, Basma Abd Elmoneim, Tarek Fawzy, Suzan F Omar
Department of Radiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||30-Jun-2014|
|Date of Acceptance||29-Sep-2014|
|Date of Web Publication||18-Mar-2016|
Suzan F Omar
MBBCh, MSc, Radiology Department, Faculty of Medicine, Menoufia University, Menoufia
Source of Support: None, Conflict of Interest: None
This study aimed to evaluate the role of proton magnetic resonance spectroscopy ( 1 H-MRS) in grading of brain gliomas.
Noninvasive and accurate grading of brain gliomas is important for determining the correct treatment plane and in some cases to avoid unnecessary aggressive surgical treatment. 1 H-MRS has a potential for providing metabolic information about tumor tissues without surgical tissue sampling.
Patients and methods
This prospective study included 70 patients with brain gliomas. Single voxel spectroscopy was obtained using PRESS sequence with TE 136 ms.
The number of male and female patients was 38 and 32, respectively; their ages ranged from 11 to 58 years with a mean age of 49.9 years. The mean Cho/Cr ratio was 1.46 in low-grade gliomas and 3.9 in high-grade gliomas. The mean Cho/N-acetylaspartate was 1.17 in low-grade gliomas and 3.7 in high-grade gliomas. Lipid/lactate peak was present only in high-grade gliomas.
1 H-MRS is a noninvasive method that provides greater information concerning tumor activity and characterization of the tumor tissue than is possible with standard MRI technique alone.
Keywords: Brain gliomas, grading, MRI, magnetic resonance spectroscopy
|How to cite this article:|
Hafez H, Elmoneim BA, Fawzy T, Omar SF. The role of proton magnetic resonance spectroscopy in grading of brain gliomas. Menoufia Med J 2016;29:136-40
|How to cite this URL:|
Hafez H, Elmoneim BA, Fawzy T, Omar SF. The role of proton magnetic resonance spectroscopy in grading of brain gliomas. Menoufia Med J [serial online] 2016 [cited 2019 Sep 21];29:136-40. Available from: http://www.mmj.eg.net/text.asp?2016/29/1/136/179004
| Introduction|| |
Gliomas are the most common primary tumors of the central nervous system. These tumors are classified into low-grade astrocytoma (grade I/II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (GBM) (grade IV). There is, however, significant variation in the clinical course of these lesions and in approach to therapy .
Noninvasive and accurate grading of brain gliomas is important for determining the correct treatment plan and in some cases to avoid unnecessary aggressive surgical treatment .
MRI in particular has emerged as the imaging modality most frequently used to evaluate intracranial tumors . MRI is an excellent method for anatomical and structural diagnosis of the brain; however, it does not provide information on tumoral vascularity, metabolism, and cellularity, which are important in grading the tumor .
Proton magnetic resonance spectroscopy ( 1 H-MRS) is a noninvasive technique used to obtain a biochemical profile of brain tissue and can provide biomarkers of neuronal integrity, cell proliferation or degradation, energy metabolism, and necrotic transformation of tissues that complement the anatomical information available from conventional MRI  [Figure 1],[Figure 2],[Figure 3] and [Figure 4].
|Figure 1: Case no. 1: Axial T1WI, axial FLAIR, postcontrast (axial, sagittal), and magnetic resonance spectroscopy spectrum of anaplastic astrocytoma (grade III) .|
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|Figure 2: Case no. 2: Axial T1WI, axial FLAIR, postcontrast (axial, coronal), and magnetic resonance spectroscopy spectrum of low-grade glioma (grade II) .|
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|Figure 3: Case no. 3: Axial T1WI, axial T2WI, postcontrast (axial, sagittal), and magnetic resonance spectroscopy spectrum of glioblastoma multiforme (grade IV) .|
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|Figure 4: Case no. 4: Axial T1WI, axial T2WI, coronal T2WI, axial postcontrast, and magnetic resonance spectroscopy spectrum of low-grade glioma (grade II) .|
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Various metabolites in brain tissue, such as N-acetylaspartate (NAA), choline compounds (Cho), creatine and phosphocreatine (Cr), lactate, and lipid can be measured using 1 H-MRS .
1 H-MRS can improve the diagnostic accuracy preoperatively in brain tumors, even obviating stereotactic biopsies in some cases (especially the inoperable tumors) and helping in the monitoring of treatment response and the evaluation of tumor recurrence, as metabolic changes are often detectable before structural changes become evident on MRI .
This study aimed to evaluate the role of 1 H-MRS in grading of brain gliomas.
| Patients and methods|| |
This prospective study was conducted on 70 patients with brain gliomas presenting by various symptoms; it included 38 male and 32 female patients with age ranging between 11 and 85 years. All patients underwent MRS. MRS was performed using single voxel point-resolved spectroscopy (PRESS) with a volume of interest 1 × 1 × 1 cm and presaturation bands placed around volume of interest. We have positioned the possible voxel within the solid tumoral tissue avoiding areas of cysts, normal appearing brain parenchyma, scalp, or bone. Automatic shimming of the linear X, Y, Z channels was used to optimize field homogeneity; water resonance and water suppression pulses were optimized for the consistent water saturation.
Proton spectrum was recorded with TR 2000 ms, TE 136 ms, slice thickness 20 mm, matrix 128 × 256, FOV 20 mm, number of acquisition 128, and duration of scan was 4 min 16 s. The peak amplitude of NAA, Cr, Cho, lactate, and lipids was obtained and the ratios of Cho/Cr, Cho/NAA, and NAA/Cr were calculated and correlated to the pathological findings.
| Results|| |
This study included 70 patients, 38 male and 32 female patients. Their ages ranged from 11 to 58 years with mean age of 49.9 years. The most affected age group was between 40 and 50 years. The patients presented by wide range of neurological symptoms; headache was the most presenting symptom (57.1%). The most affected region of the brain was the parietal lobe. After verification of conventional MRI and MRS findings against histopathological data, the examined patients were subdivided into two groups: low-grade glioma (45.71%) and high-grade glioma (54.29%). In low-grade gliomas, 68.75% were surrounded with grade I vasogenic edema. No enhancement and homogenous enhancement were the most encountered enhancement pattern (31.25%). MRS data analysis revealed mean Cho/Cr ratio ranging from 1.1 to 1.85 with mean ratio 1.46, Cho/NAA ratio ranging from 1 to 3.2 with mean ratio 1.17, and NAA/Cr ratio ranging from 0.74 to 2.2 with mean ratio 1.36 [Table 1]. Lactate peak was detected in nine cystic lesions. In high-grade gliomas, 50% were surrounded with grade III vasogenic edema. Heterogeneous enhancement was the most encountered enhancement pattern (42.11%). MRS data analysis revealed Cho/Cr ratio ranging from 1.9 to 11.87 with mean ratio 3.9, Cho/NAA ratio ranging from 2.01 to 10.8 with mean ratio 3.7, and NAA/Cr ratio ranging from 0.49 to 1.8 with mean ratio 1.2 [Table 1]. Lactate/lipid peak was detected in 20 cases. Inverted lipid peak was detected in 10 cases. Conventional MRI gave false results in 78.5% of low-grade gliomas and in 94.7% of high-grade gliomas; however, MRS results and histopathological results were identical [Table 2].
| Discussion|| |
Conventional MRI provides important information regarding contrast material enhancement, perifocal edema, border definition, hemorrhage, necrosis, and mass effects, which are helpful in characterizing tumor aggressiveness and apparent histological grade of glioma. However, sensitivity and specificity for predicting tumor grade have been considered insufficient and unsatisfactory .
Hartmann et al.  pointed that, despite optimization of sequences and protocols, the classification and grading of gliomas with conventional MRI is sometimes unreliable, with the sensitivity for glioma grading ranging from 55.1 to 83.3%.
In histopathological grading of gliomas, tumor cellularity and vascularity are the major factors to be determined. Providing reliable information about these factors on conventional MRI is not possible .
Law et al.  stated that accurate tumor grading has important implications for treatment planning. Patients with an erroneous diagnosis of high-grade gliomas will undergo unnecessary adjuvant therapy; patients with an erroneous diagnosis of low-grade gliomas will be treated conservatively, with concomitant morbidity and mortality.
MRS is a method for analyzing the metabolism of organs and cells, biochemical changes, and quantitative analysis of compounds in humans. Various metabolites in brain tissue, such as NAA, Cho, Cr, lactate, and lipid, can be measured using 1 H-MRS .
The MRS characteristic of glioma includes a significant reduction in NAA and in Cr and an elevation of Cho. Reduction of NAA reflects loss of neuronal elements, as they are destroyed and/or replaced by malignant cells. Reduced Cr is probably related to an altered metabolism. Elevation of Cho reflects increased membrane synthesis and cellularity .
Gliomas commonly have distinct imaging features by which low-grade growths can be differentiated from high-grade types. Low-grade gliomas are generally characterized by a relatively high concentration of NAA, low level of Cho, and absence of lactate and lipids. The increase in Cr concentration indicates low-grade gliomas .
Murphy et al.  pointed that, regarding MRS, elevation in Cho with decrease in NAA is a reliable indicator of tumor. There is extensive literature demonstrating the metabolite ratios of Cho/Cr, NAA/Cr, and the presence of lipids and lactate to be useful in grading tumors and predicting tumor malignancy.
Yang et al.  found that tumor grades can be differentiated with a high degree of precision and that Cho/NAA and Cho/Cr ratios are highly correlated with tumor grade. In the current study, high-grade gliomas tend to display higher mean Cho/NAA and Cho/Cr ratios compared with low-grade gliomas, although the study population was only small. This suggests that histological results generally correlate with the findings from preoperative 1 H-MRS.
Law et al.  pointed that the quantitative method is much more informative when used in grading of cerebral gliomas. Their study was performed on 160 patients who were diagnosed as gliomas on the basis of conventional MRI and yielded that significant difference was noted in Cho/Cr, Cho/NAA, and NAA/Cr ratios between low-grade and high-grade gliomas.
Although this study was performed on less number of patients than the study by Law et al. , most of our values were more or less close to their study. However, the main difference was seen in the mean Cho/Cr ratio for high-grade glioma, which was 3.9 in our study and 2.5 in theirs, and this is mostly probably due to the large difference in the number of patients.
NAA is present mainly in normal neurons and is recognized as an internal neuronal marker. In normal brain, NAA produces the highest peak on 1 H-MRS examination. Izumiyama et al.  reported that glioma malignancy tends to increase with decreases in NAA. In the present study, the decreases in NAA in all the gliomas reflected the fact that the neurons had been encroached upon and replaced by neoplasm, leading to decreased numbers of neurons and decline in signal strength.
In contrast to NAA, Cho signal intensity is always high in gliomas and increases at a higher rate with more rapid development of the neoplasm. Cho is one of the components of metabolites of the membrane and reflects membrane turnover. Elevation of the Cho peak found in the present study is likely due to rapid cellular proliferation, as a result of increased mitosis, leading to abnormal increase in membrane metabolism and subsequent cellular destruction. Researchers have thus identified the Cho peak as a marker of tumor cell proliferation .
Another peak that has been observed in brain tumors is lactate with prominent peaks at 0.9 and 1.3 ppm. Lactate is the end product of the nonoxidative glycolysis, and therefore its presence may be attributed to rapid tumor growth, with subsequent hypoxia and necrosis in the tumor tissue and indicates high tumoral grade .
According to Li et al. , lipid peaks are mostly observed in high-grade tumors, particularly in GBM, and indicate necrosis and disruption of the myelin sheath. The lipid has a peak at 0.8-1.3 ppm. Li et al.  pointed in their study that none of the diagnosed low-grade gliomas had a lipid peak, whereas most high-grade gliomas (80% of the high-grade gliomas) had elevated lipid peaks.
This is in agreement with our study in which 20 (52.6%) of the high-grade gliomas showed elevated lactate/lipid peak and 10 (26.3%) lesions showed lactate peak. These findings show that the presence or elevation of lactate and lipid peaks is detected in patients with higher tumor malignancy.
In our study, nine (28.1%) cases of low-grade gliomas showed lactate peak, especially lesions that have a cystic component. This is in agreement with the study by Herholz et al.  who stated that lactate tends to accumulate in tumor cysts. This was also consistent with results of studies conducted by Elshafey et al.  and Lai et al.  who stated that all cystic tumors and abscesses in their study showed findings of increased lactate, which is a nonspecific metabolite that results from anaerobic glycolysis.
Some reports have shown the usefulness of several metabolite ratios to distinguish between low-grade and high-grade gliomas, including Cho/NAA and Cho/Cr. Yang et al.  found that tumor grades can be differentiated with a high degree of precision and that Cho/NAA and Cho/Cr ratios correlate well with tumor grades. In the current study, GBM tended to display high mean Cho/NAA and Cho/Cr ratios compared with low-grade gliomas, although the study population was small. This suggests that histological results generally correlate with the findings from preoperative 1 H-MRS.
Zonari et al.  and Di Costanzo et al.  stated in their studies that combining MRS and perfusion-weighted imaging can improve the discrimination accuracy between high-grade and low-grade gliomas up to 100%. In this current study, combining MRS and conventional MRI improved the accuracy of the discrimination between low-grade and high-grade gliomas.
| Conclusion|| |
1 H-MRS can help identify the grade of brain tumor, which has important implications for clinical management. A brain lesion with high Cho/NAA and Cho/Cr and low NAA/Cr ratios is most likely to be high-grade malignancy, and lipid/lactate peaks were also frequently seen in more malignant lesions.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jeuna SS, Kima MC, Kim BS, Lee JM, Chung ST, Hyun CO, et al.
Assessment of malignancy in gliomas by 3T 1H MR spectroscopy. Clin Imaging 2005; 29
Chang HJ, Burke AE, Glass RM. Gliomas. JAMA 2012; 303:1000-2.
Al-Okaili RN, Krejza j, Wang S. Advanced MR imaging techniques in the diagnosis of intraaxial brain tumors in adults. Radiographics 2006; 26
Hourani R, Brant LJ, Rizk T. Can proton MR spectroscopic and perfusion imaging differentiate between neoplastic and nonneoplastic brain lesions in adults? Am J Neuroradiol 2008; 29
Nagar VA, Ye J, Xu M. Multivoxel MR spectroscopic imaging - distinguishing intracranial tumors from non-neoplastic disease. Ann Acad Med 2007; 36
Aydin H, Sipahioglu S, Oktay NA, Altin E, Kizilgoz V, Hekimoglu B. The value of proton MR-spectroscopy in the differentiation of brain tumors from non-neoplastic brain lesions. JBR-BTR 2011; 94
Kumar A, Kaushik S, Tripathi RP. Role of in vivo proton MR spectroscopy in the evaluation of adult brain lesions: our preliminary experience. Neuroradiol India 2003; 51
Fayed N, Morales H, Modrego PJ, Pina MA. Contrast/noise ratio on conventional MRI and choline/creatine ratio on proton MRI spectroscopy accurately discriminated low-grade from high-grade cerebral gliomas. Acad Radiol 2006; 13
Hartmann M, Jansen O, Heiland S, Sommer C, Munkel K, Sartor K. Restricted diffusion within ring enhancement is not pathognomonic for brain abscess. Am J Neuroradiol 2001; 22
Oshiro S, Tsugu H, Komatsu F, Abe H, Onishi H, Ohmura T, et al.
Quantitative assessment of gliomas by proton magnetic resonance spectroscopy. Anticancer Res 2007; 27
Law M, Yang S, Babb JS, Knopp EA, Golfinos JG, Zagzag D, et al.
Comparison of cerebral blood volume and vascular permeability from dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade. Am J Neuroradiol 2004; 25
Burtscher IM, Holtas S. Proton magnetic resonance spectroscopy in brain tumors: clinical applications. Neuroradiology 2001; 43
Bulik M, Jancalek R, Vanicek J. Potential of MR spectroscopy for assessment of glioma grading. Clin Neurol Neurosurg 2013; 115
Murphy PS, Viviers L, Abson C, Rowland IJ, Brada M, Leach MO, et al.
Monitoring temozolomide treatment of low-grade glioma with proton magnetic resonance spectroscopy. Br J Cancer 2004; 90
Yang D, Korogi Y, Sugahara T, Kitajima M, Shigematsu Y, Liang L, et al.
Cerebral gliomas: prospective comparison of multivoxel 2D chemical-shift imaging proton MR spectroscopy, echoplanar perfusion and diffusion weighted MRI. Neuroradiology 2002; 44
Izumiyama H, Abe T, Tanioka D, Fukuda A, Kunii N. Clinicopathological examination of glioma by proton magnetic resonance spectroscopy background. Brain Tumor Pathol 2004; 21
Fountas KN, Kapsalaki EZ, Vogel RL, Fezoulidis I, Robinson JS, Gotsis ED. Noninvasive histologic grading of solid astrocytomas using proton magnetic resonance spectroscopy. Stereotact Funct Neurosurg 2004; 82
Catalaa I, Henry R, Dillon WP, Graves EE, Mcknight TR, Lu Y, et al.
Perfusion, diffusion and spectroscopy values in newly diagnosed cerebral gliomas. NMR Biomed 2006; 19
Li X, Vigneron DB, Cha S, Graves EE, Crawford F, Chang SM, et al.
Relationship of MR-derived lactate, mobile lipids, and relative blood volume for gliomas in vivo. Am J Neuroradiol 2005; 26
Herholz k, Heindel W, Luyten PR. In vivo imaging of glucose consumption and lactate concentration in human gliomas. Ann Neurol 1992; 31
Elshafey R, Hassanein O, Shakal A, Mokbel E. H proton MR spectroscopy and diffusion-weighted imaging in discrimination between pyogenic brain abscesses and necrotic brain tumors. Egypt J Radiol Nucl Med 2013; 77
Lai PH, Ho JT, Chen WL. Brain abscess and necrotic brain tumor: discrimination with proton MR spectroscopy and diffusion-weighted imaging. Am J Neuroradiol 2002; 23
Zonari P, Baraldi P, Crisi G. Multimodal MRI in characterization of glial neoplasm: combined role of single-voxel MR spectroscopy, diffusion imaging and echo-planer perfusion imaging. Neuroradiology 2007; 49
Di Costanzo A, Scarabino T, Trojsi F, Giannatempo GM, Popolizio T, Catapano D. Multiparametric 3T MR approach to the assessment of cerebral gliomas: tumor extent and malignancy. Neuroradiology 2006; 4:622-631.
[Table 1], [Figure 1], [Figure 2], [Figure 3], [Figure 4]