Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) in the analysis of possible pathways and patterns of infiltration of malignant glioma

The purpose of this study was to investigate the use of advanced MRI techniques like diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) in the detection of possible early signs of infiltrating malignant glioma cells in patients with untreated anaplastic astrocytoma (AA) and glioblastoma (GBM). They are the most common primary brain tumors are and, even in early stages, tend to excessive migration and invasion in the surrounding brain areas. In histopathological studies, malignant glioma cells were found in macroscopically normal appearing brain tissue far away from the primary lesion, even in the contralateral hemisphere. The widespread infiltration throughout the brain parenchyma is one of the main reasons for the difficulties in the treatment and the poor prognosis for patients with malignant brain tumors. Since these tumors tend to spread along horizontal nerve fibers, the corpus callosum (CC) plays a central role by consisting of the largest fiber bundle in the human brain and interconnecting both hemispheres. An approach to detect these malignant microinvasive tumor cells is provided by advanced MRI-techniques like DWI and DTI, revealing data about local diffusion on a microstructural level. It was found, that in early stages, diffuse interneural infiltration goes along with changes of the apparent diffusion coefficient (ADC) while with the progression of tumor growth and thereby destruction of fiber bundles, changes of the fractional anisotropy (FA) can be detected. In this study, 31 patients (12 female and 19 male, mean age 57.6 years) with high-grade brain tumors (8 AA WHO III°, 23 GBM WHO IV°) were examined preoperatively, by MRI at 3 Tesla, using a high-resolution DTI-sequence. ADC- and FA-values were analyzed in the tumor-associated region of the CC, which were identified by fiber tracking. In addition, ADC- and FA-values were measured in the normal appearing white matter of the hemisphere contralateral to the primary tumor. Diffusion data was quantified in the entire hemisphere as well as in the region mirrored to the primary lesion. These values were compared to age- and sex-matched healthy controls (8 female and 16 male, mean age 58.7 years). Before, patients were divided into two subgroups. One consisting of patients with macroscopical infiltration of the CC seen in conventional MRI (“pat w inf”, 9 patients) and the other with the patients without infiltration of the CC (“pat w/o inf”, 22 patients). In morphologically normal appearing CC the ADC values were elevated in the tumor patients compared to matched controls in both subgroups while the corresponding FA was reduced. Visible infiltration of the CC had no effect on ADC values, while with the affection of the CC FA values were significantly lower in “pat w inf” compared to “pat w/o inf”. The data of the analysis of the entire contralateral hemisphere revealed an increase in ADC and a decrease in FA compared to healthy controls. Analogues results were found in the region of intrerest-measurement in the area mirrored to the brain tumor. While there was no difference in FA values of the mirrored region to the entire contralateral hemisphere, ADC values were significantly higher in the brain region mirrored to the tumor. As an early indicator for transcallosal infiltration of malignant glioma, changes in diffusivity can be detected in unsuspicious regions of the CC. Being affected by multiple factors, ADC values seem not to reflect the degree of tumor progress, while lower FA values appear to go along with a higher grade of destruction. An elevation of the ADC and reduction of FA can also be found in the brain parenchyma of the hemisphere contralateral to the primary tumor. In the absence of visible MR-imaging abnormalities, this may as well be an indicator for the presence of malignant glioma cells in macroscopically normal appearing brain tissue. The invasion of the contralateral hemisphere seems to be initiated in the brain parenchyma mirrored to the primary lesion rather than being a multifocal process