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Neuroradiology |
1 From the Departments of Neuroradiology (E.G., S.P., O.V., X.Q.D., J.F., T.K., H.Z.), Neurosurgery (O.H., M.W.), and Neuropathology (C.H.), University of Hamburg, Martinistrasse 52, 20251 Hamburg, Germany. Received January 13, 2005; revision requested March 31; revision received April 8; final version accepted May 2. Address correspondence to E.G. (e-mail: goebell{at}uke.uni-hamburg.de).
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ABSTRACT |
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Materials and Methods: The study protocol was approved by the local ethics committee, and written informed consent was obtained. Diffusion-tensor MR imaging was performed in 23 patients (15 men, eight women; mean age, 47 years) with histologically confirmed brain gliomas. Eleven of the 23 tumors were low-grade gliomas (WHO grade II) and 12 were anaplastic gliomas (WHO grade III). Regions of interest were placed in the tumor center, tumor border, normal-appearing white matter (NAWM) adjacent to the tumor, and NAWM of the contralateral hemisphere. fractional anisotropy (FA) ratios were calculated for regions of interest in relation to the NAWM of the contralateral hemisphere. Pairwise comparisons were performed by using the Mann-Whitney U test.
Results: Median FA ratios for grade II versus grade III gliomas were 0.406 versus 0.405, respectively, for tumor center, 0.733 versus 0.449, respectively, for tumor border, and 0.962 versus 0.943, respectively, for NAWM adjacent to the tumor. Differences in FA ratio between low-grade and high-grade tumors were significant in the tumor border only (P = .01). Differences in FA ratio were not significant between low-grade and high-grade gliomas in the tumor center or in the NAWM adjacent to the tumor.
Conclusion: The periphery of low-grade gliomas contains a considerable amount of preserved fiber tracts. In high-grade gliomas, however, most of these tracts are disarranged. Low FA ratios in the tumor center are consistent with a high degree of disorganization of myelinated fiber tracts in the center of both low-grade and high-grade gliomas.
© RSNA, 2006
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Anaplastic gliomas are usually treated in the same way that grade IV tumors, such as glioblastoma multiforme, are treated—that is, with tumor resection and additional radiation and chemotherapy. In grade II gliomas, only surgical treatment for histologic confirmation or tumor resection is performed in most patients (4,5). In most of these grade II and grade III tumors, which lack central necrosis and/or peripheral edema, the morphologic aspect does not indicate preservation or destruction of myelinated fiber tracts within the tumor center or tumor border. Clinical impairment is slight in most patients with grade II and grade III gliomas and does not indicate whether the fiber tracts are invaded or displaced.
Diffusion-tensor MR imaging can be used to describe the direction of molecular water movement within tissues. The restriction of water diffusibility measured as fractional anisotropy (FA) is correlated with the integrity of myelinated fiber tracts (6,7). In studies that investigated white matter tract invasion by using diffusion-tensor MR imaging, researchers described substantial changes in the FA of brain tumors and the surrounding edema (3,8,9). To our knowledge, however, only a few gliomas without central necrosis and/or peripheral edema have been investigated so far.
The purpose of our study, therefore, was to prospectively evaluate whether diffusion-tensor MR imaging depicts differences in WHO grade II and III glial brain tumors on the basis of tumor architecture and peritumoral tract invasion.
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MATERIALS AND METHODS |
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MR Imaging Parameters
The examinations were performed with a 1.5-T MR imaging unit (Sonata; Siemens, Erlangen, Germany) and included transverse T2-weighted (turbo spin-echo) triple-echo MR imaging, magnetization transfer, diffusion-weighted MR imaging, diffusion-tensor MR imaging, chemical shift hydrogen spectroscopy, and transverse T1-weighted spin-echo MR imaging performed before and after intravenous administration of 0.1 mmol per kilogram body weight gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany). Technical parameters of diffusion-tensor MR imaging included a single-shot spin-echo echo-planar diffusion-tensor sequence, echo-planar factor of 96, 4900/90 (repetition time msec/echo time msec), diffusion gradient encoding in six directions, b values of 0–1500 sec/mm2, section thickness of 3 mm, no intersection gap, field of view of 230 mm, 128 x 128 matrix interpolated into a 256 x 256 matrix, and acquisition time of 5 minutes 14 seconds.
Image Analysis
FA maps.—FA maps were created by using a diffusion-tensor MR imaging task card that was implemented on the MR imaging console with the standard formula
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1, 2, and 3 are the three eigenvalues describing a diffusion tensor and is one-third times the sum of these three eigenvalues. The software that was used to perform this technique was supplied by researchers at Massachusetts General Hospital (Gregory Sorensen and Ruopeng Wang, Nuclear Magnetic Resonance Center, Massachusetts General Hospital, Boston, Mass). Coregistration of all modalities.—Distortion artifacts from the echo-planar MR imaging sequence were corrected by coregristration and resectioning with 126-msec T2-weighted spin-echo MR images by using SPM99 software (Wellcome Department of Imaging Neuroscience, University College London, England) in Matlab (MathWorks, Natick, Mass).
Region of interest determination.—For each patient, four regions of interest (ROIs) of similar size (120–180 voxels) were placed on the 126-msec T2-weighted spin-echo MR image (E.G., with 8 years of experience). ROIs were placed in the tumor center, tumor border, normal-appearing white matter (NAWM) adjacent to the tumor, and NAWM of the contralateral hemisphere by using MRIcro (Chris Roden, University of Nottingham, UK). The ROIs in the tumor center and tumor border were fully covered by tumor tissue. ROIs in the tumor border were positioned in the periphery of the tumor as close to the tumor border as possible without contacting white matter. For the NAWM adjacent to the tumor, ROIs were placed in the NAWM and were positioned close to the tumor border without contacting the tumor tissue. For the NAWM of the contralateral hemisphere, ROIs were positioned in the white matter of the contralateral hemisphere and covered the same site as the white matter near the tumor. If possible, contact with gray matter was avoided. In case of gray matter contact in the NAWM adjacent to the tumor, ROIs in the NAWM of the contralateral hemisphere were positioned in the corresponding site of the contralateral hemisphere (Fig 1).
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RESULTS |
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The degree and orientation in restriction of free water protons in the brain are predominantly influenced by the size and shape of extra- and intracellular spaces. The phenomena of diffusion-weighted MR imaging correlate well with the physiologic and pathologic factors of brain tissue, especially in patients with ischemic stroke (10). The exact biophysical correlates of diffusion restriction, however, are not fully understood and are an object of controversial discussion (11,12).
The hope that mean diffusibility in brain tumors would be a parameter for tumor classification has not been realized in previous studies (13–15). Mean diffusibility in brain tumors is influenced by tumor cellularity, intra- or extracellular edema, and tumor necrosis (16). This multifactorial influence makes mean diffusibility a rough parameter for tumor infiltration and does not give a specific perception of tumor classification. Mean diffusibility is not directly dependent on the integrity of myelinated fiber tracts.
In contrast to mean diffusibility, FA depends on the restriction of water proton movement along myelinated fiber tracts (12). Tumor cells that spread along fiber tracts cause displacement, deviation, or disruption of these tracts. A relevant reduction in the FA of brain tumors has been evaluated in previous studies (8,9,17,18). Growth of tumor cells does not necessarily result in a directional vector of proton movement because FA is reduced. On the other hand, the displacement or deviation of fiber tracts does not necessarily mean FA alteration because fiber tracts might still be unharmed. Thus, the FA in infiltrated brain tissue is dependent not only on the integrity of fiber tracts but also on the percentage of tumor tissue in relation to the preserved fiber tracts. The same phenomenon has been described for peritumoral edema in which an elevation of mean diffusibility and a reduction of FA may indicate peritumoral tract invasion (3,19–21). A distinct reduction in FA in the tumor center of WHO grade IV gliomas indicates a high degree of fiber tract disorganization and correlates with unorganized tumor growth and tumor necrosis (3).
Data regarding the tissue characterization of nonnecrotic gliomas with diffusion-tensor MR imaging are limited and inconsistent. Significant differences between grade II and III gliomas were described by Inoue et al (17), who studied 41 histologically confirmed gliomas, of which nine were grade II and six were grade III tumors. The authors found higher FA values in high-grade gliomas (suggesting higher symmetry of histologic organization) compared with low-grade gliomas. These results are somewhat contradictory to the usual understanding of the microstructure of high-grade gliomas. The histologic characteristics of high-grade gliomas compared with those of low-grade gliomas reveal pleomorphologic structures and a regressive organization rather than an increase in parallel histologic organization. Other groups found no significant difference between these two tumor groups (22,23).
In contrast to these studies, we evaluated regional differences within gliomas and did not calculate the average value of the FA covering the whole tumor. To the best of our knowledge, ours is the first study to report on the regional differences in median FA values for brain gliomas and to eliminate the bias of tumor necrosis. Our data indicate a high degree of fiber tract disorganization in the center of low- and high-grade tumors. FA values in the tumor center revealed no significant difference between grade II and III gliomas. Without correction for the extensive variance of FA values in NAWM by calculating ratios of median FA values from the tumor center and contralateral hemisphere, no differences have been noted in prior studies between grade II and III tumors (22,24). In our study, the periphery of the high-grade gliomas showed a significant difference in FA values in comparison with the periphery of low-grade tumors (P = .01). The reduction in FA values—evident in both primary absolute values and ratios that were used to eliminate physiologic inhomogeneity of the FA—indicates a considerable preservation of fiber tracts at the periphery of low-grade tumors, whereas tumor infiltration and fiber tract disorganization in the periphery of grade III tumor is more distinct.
Peritumoral fiber tract deviation or infiltration investigated with diffusion-tensor MR imaging has been noted in several previous studies (8,9,19,21,25). Most of these studies focused on peritumoral fiber tract infiltration or deviation in patients with peritumoral signal intensity changes that were visible on T2-weighted MR images. Only a few patients with low- or high-grade tumors that lacked peripheral edema have been reported. Price et al (25) found abnormalities in the FA values of NAWM on T2-weighted MR images in patients with high-grade gliomas (grade III, n = 3; grade IV, n = 10). No abnormalities, however, were found in patients with low-grade tumors (n = 3). Tropine et al (8) described no significant changes in FA values of adjacent white matter in low-grade tumors (n = 8). We similarly found no relevant change in the FA values of NAWM adjacent to the tumor (grade II and III). Our results and those of previous studies show that fiber tract destruction that is not visible on T2-weighted MR images in the vicinity of tumors without peripheral edema cannot be postulated from diffusion-tensor MR imaging data. Deviation or compression of fiber tracts might exist in the vicinity of the tumor but may not be visible on conventional MR images or be measurable with FA. Integrating FA values and color-coding diffusion-tensor MR imaging maps or spectroscopic data in future studies may give further perception of the functionality of fiber tracts in brain gliomas and make diffusion-tensor MR imaging more sensitive for treatment decisions.
Our study has limitations. The first limitation is that only a relatively small number of patients were investigated. Second, we admit that the radiation therapy applied to three patients with grade III tumors may have influenced the FA values that were measured in the gliomas or adjacent white matter. ROIs in these patients, however, were placed in tumor regions that were not visible as tumor during primary treatment, and therefore these areas were not the target of radiation therapy.
Another limitation may be the placement of ROIs. Even if the ROIs are carefully placed, some partial volume effects of brain or tumor tissue that should not be included may have an influence on the results.
In conclusion, diffusion-tensor MR imaging demonstrates that the periphery of low-grade gliomas (grade II) contains preserved fiber tracts, whereas most of these tracts are disarranged in high-grade gliomas (grade III). This might serve as a differential diagnostic criterion in the future, but more patient studies are needed for confirmation. Low FA ratios in the tumor center are consistent with a known high degree of disorganization of myelinated fiber tracts in the center of both low- and high-grade gliomas.
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FOOTNOTES |
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Abbreviations: FA = fractional anisotropy • NAWM = normal-appearing white matter • ROI = region of interest • WHO = World Health Organization
Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, E.G., H.Z.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, E.G., O.V., X.Q.D., O.H., J.F., H.Z.; clinical studies, E.G., S.P., O.H., C.H., M.W., H.Z.; experimental studies, E.G., S.P., O.V., X.Q.D., T.K.; statistical analysis, E.G., O.V., X.Q.D., J.F., T.K.; and manuscript editing, E.G., O.H., J.F., T.K., C.H., M.W., H.Z.
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References |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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