ImagingFractional anisotropy value by diffusion tensor magnetic resonance imaging as a predictor of cell density and proliferation activity of glioblastomas
Introduction
Essentially, the diffusion of water molecules displays microscopic random (Brownian) translational motion, and under these conditions, the molecular mobility of water is the same in all directions. In vivo, water diffusion takes on an abnormal motion due to hindrance by the presence of complex microstructural barriers in tissue, such as white matter tracts, cell membranes, and/or capillary vessels, and consequently the change in magnitude and directionality of water diffusion arises in a 3-dimensional space [2]. This directional variation is termed diffusion anisotropy. Diffusion tensor magnetic resonance imaging (DTI) provides quantitative information about the magnitude and directionality of water diffusion along a vector in a 3-dimensional space [4], [6], [17], [26]. Evaluation of directionality of water diffusion using DTI has recently become available for visualization of cerebral fiber tracts [26] and demonstration of substantial differences among the various lesions of multiple sclerosis [1], [7], [8], [24]. In DTI, a set of orthogonal vectors known as eigenvectors, which define the orientation of the principal axes of a diffusion ellipsoid in space, are calculated from the diffusion tensor. The length of each vector is represented by corresponding eigenvalues. The fractional anisotropy (FA) is derived from eigenvectors for quantification of anisotropy. A FA value is calculated using the following formula based on eigenvalues in the diffusion tensor [2], [18]:where λ1, λ2, and λ3 are the largest, intermediate, and smallest eigenvalues, respectively, of the diffusion tensor. The FA is expressed as a numerical value between 0 and 1 without a unit. A higher FA value implies a greater degree of anisotropic motion of water molecules.
Presurgical knowledge of the cell density and proliferation potential of the tumor tissue would have prognostic significance and help to elucidate the histologic characteristics in individual patients with astrocytic tumors. Water diffusion has been suggested to be affected by tumor cellularity in gliomas [22]. Our preliminary study suggested a correlation between the FA value and the tumor cell density or malignancy grades in astrocytic tumors [3], which led to the presumption that FA values also correlate with the cell proliferation activity of astrocytic tumors. To date, whether FA can act as an indicator of cell proliferation in astrocytic tumors is unknown. The quantitative estimation of cell density or proliferation is largely complicated by widely distributed values of differently graded astrocytic tumors when a study involves a group of mixed, differently graded tumors. To confirm whether FA values indicate cell density and proliferation activity of an astrocytic tumor group limited to 1 type, we examined the relationship among FA value, tumor cell density, and MIB-1 index, which is widely used as a quantitative information of cell proliferation [10], [12], [19], [25] in glioblastomas alone.
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Patient population
The study protocol was approved by the Ethics Committee of Iwate Medical University (Morioka, Japan). The patients recruited to this study were admitted to the Department of Neurosurgery, Iwate Medical University, between September 2000 and December 2002. Entry criteria for this study were as follows: (A) adult patients who were diagnosed with supratentorial glioblastoma; (B) patients whose tumor was primarily in the cerebral white matter, except for the basal ganglia, corpus callosum,
Results
The mean FA values of the corpus callosum (the genu in 9 patients and the splenium in 10 patients), subcortical white matter (the frontal lobe in 9 patients and the occipital lobe in 10 patients), and glioblastoma lesion were 0.70 ± 0.05, 0.32 ± 0.04, and 0.24 ± 0.05, respectively. The mean FA values were significant different among the corpus callosum, subcortical white matter, and glioblastoma tissue (P < 0.05; Fig. 2).
In glioblastoma lesions, the mean values of cell density and MIB-1 index
Discussion
Normal white matter shows strong directionality of water diffusion and, consequently, a high FA value, because the water diffusion parallel to the white matter tracts is less restricted than the water diffusion perpendicular to them [26]. Although limited information is available for the subcortical NWM and corpus callosum, FA values are 0.2 to 0.6 in the frontal lobe [7], [8], [21], [24], [28] and 0.6 to 0.8 in the corpus callosum [1], [7], [8], [16], [21]. The FA values in the present study
Acknowledgments
This study was supported in part by a grant-in-aid for Advanced Medical Science Research from the Ministry of Science, Education, Sports and Culture, Japan.
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