Abstract

Primary brain tumors comprise 28% of all tumors and 80% of malignant tumors. Pathophysiology of high-grade gliomas includes significant distortion of white matter architecture, necrosis, the breakdown of the blood brain barrier, and increased intracranial pressure. Diffusion tensor imaging (DTI), a diffusion weighted imaging technique, can be used to assess white matter architecture. Use of DTI as a non-invasive pathophysiological tool to analyze glioma impact on white matter microstructure has yet to be fully explored.Preliminary assessment of DTI tractography was done as a measure of intracranial tumor impact on white matter architecture. Specifically, we addressed three questions: 1) whether glioma differentially affects local white matter structure compared to metastasis, 2) whether glioma affects tract integrity of major white matter bundles, 3) whether glioma lobe localization affects tract integrity of different white matter bundles.In this study, we retrospectively investigated preoperative DTI scans from 24 patients undergoing tumor resection. Fiber tractography was estimated using a deterministic fiber tracking algorithm in DSI (diffusion spectrum imaging) Studio. The automatic anatomical labeling (AAL) atlas was used to define the left and right (L/R) hemisphere regions of interest (ROI). In addition, the John Hopkins University (JHU) White Matter Atlas was used to auto-segment major white matter bundle ROIs. For all tracts derived from ROI seed targets, we computed the following parameters: tract number, tract length, fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD).The DTI tractography analysis revealed that white matter integrity in the hemisphere ipsilateral to intracranial tumor was significantly compromised compared to the control contralateral hemisphere. No differences were observed between high vs low-grade gliomas, however, gliomas induced significantly greater white matter degradation than metastases. In addition, targeted analysis of major white matter bundles important for sensory/motor function (i.e., corticospinal tract and superior longitudinal fasciculus) revealed tract-parameter specific susceptibility due to the presence of the tumor. Finally, major tract bundles were differentially affected based on lobar localization of the glioma.These DTI-based tractographic analyses complement findings from gross histopathological examination of glioma impact on neural tissue. Global and focal white matter architecture, ipsilateral to glioma, shows higher rates of degradation or edema – based on DTI tractographic metrics – in comparison to normal brain or metastases. Gliomas, which arise in the parietal lobe, also have a higher negative impact (potentially due to increased edema) on white matter integrity of the superior longitudinal fasciculus(SLF) than those which arise in the frontal lobe. Future studies will focus on using preoperative and postoperative tractography to predict functional deficits following resective surgery.

Highlights

  • Gliomas are tumors which arise from glial cells, astrocytes, oligodendrocytes, and/or ependymal cells [1]

  • Four major measures of tract integrity can be derived from estimation of the diffusion coefficient: fractional anisotropy (FA), which shows the degree of anisotropy in a given diffusion area, mean diffusivity (MD) which measures the diffusion of water molecules within a given voxel, independent of anisotropy, axial diffusivity (AD) which refers to the water diffusion parallel to white matter fibers and is proportional to axonal damage, and radial diffusivity (RD) which refers to the water diffusion perpendicular to white matter fibers and is indirectly proportional to demyelination [7]

  • This study demonstrates the use of Diffusion tensor imaging (DTI) as an anatomical and pathophysiological tool to better understand the impact gliomas have on the brain by addressing several objectives: 1) assess differences in track number and diffusivity parameters between tumor and non-tumor hemispheres: separate comparisons assessed differences between grade III/IV or grade II glioma and glioma or metastasis, 2) assess glioma impact on targeted major white matter bundles, 3) evaluate the degree to which lobe localization of the glioma effects tract integrity of targeted major sensory-motor related white matter tracts

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Summary

Introduction

Gliomas are tumors which arise from glial cells, astrocytes, oligodendrocytes, and/or ependymal cells [1]. Location, and rate of expansion, gliomas can cause damage to surrounding tissue through necrosis and hypoxia [3]. The impact of a glioma on white matter architecture and integrity is poorly understood. Diffusion tensor imaging (DTI) has been widely accepted as a preoperative neurosurgical imaging tool to assist with the demarcation of gliomas and aid in the preservation of major white matter tract function during intracranial tumor resection [5]. Studies have begun to utilize this technology to answer how gliomas affect surrounding white matter microstructure [8]

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