Diffusion Tensor Imaging Reveals Microstructural Heterogeneity of Normal-Appearing White Matter and Related Cognitive Dysfunction in Glioma Patients

Abstract

Immunohistochemical data based on isocitrate–dehydrogenase (IDH) mutation status have redefined glioma as a whole-brain disease, while occult tumor cell invasion along white matter fibers is inapparent in conventional magnetic resonance imaging (MRI). The functional and prognostic impact of focal glioma may however relate to the extent of white matter involvement. We used diffusion tensor imaging (DTI) to investigate microstructural characteristics of whole-brain normal-appearing white matter (NAWM) in relation to cognitive functions as potential surrogates for occult white matter involvement in glioma. Twenty patients (12 IDH-mutated) and 20 individually matched controls were preoperatively examined using DTI combined with a standardized neuropsychological examination. Tumor lesions including perifocal edema were masked, and fractional anisotropy (FA) as well as mean, radial, and axial diffusivity (MD, RD, and AD, respectively) of the remaining whole-brain NAWM were determined by using Tract-Based Spatial Statistics and histogram analyses. The relationship between extratumoral white matter integrity and cognitive performance was examined using partial correlation analyses controlling for age, education, and lesion volumes. In patients, mean FA and AD were decreased as compared to controls, which agrees with the notion of microstructural impairment of NAWM in glioma patients. Patients performed worse in all cognitive domains tested, and higher anisotropy and lower MD and RD values of NAWM were associated with better cognitive performance. In additional analyses, IDH-mutated and IDH-wildtype patients were compared. Patients with IDH-mutation showed higher FA, but lower MD, AD, and RD values as compared to IDH-wildtype patients, suggesting a better preserved microstructural integrity of NAWM, which may relate to a less infiltrative nature of IDH-mutated gliomas. Diffusion-based phenotyping and monitoring microstructural integrity of extratumoral whole-brain NAWM may aid in estimating occult white matter involvement and should be considered as a complementary biomarker in glioma.

Whole-tumor histogram analysis of apparent diffusion coefficient maps in grading diagnosis of ependymoma

“…Up to now, there have been many reports on ADC histogram in grading glioma, most of which are about the application of texture analysis in heterogeneity of tumors [14][15][16][17]. However, there are few reports about the use of texture analysis in ependymoma grading [18,19].…”

Structural plasticity of the bilateral hippocampus in glioma patients

“…IDH-mutation status, which represents slower local tumor growth rates and the less-infiltrative nature of diffuse tumor cell migration, has emerged as a major prognostic molecular marker in glioma patients [36][37][38][39]. Using DTI analysis, microstructural alterations in white matter distant from the tumor location in IDHwildtype glioma patients compared with IDH-mutated glioma patients were observed, which may be attribute to tumor cell invasion with fiber compression and ensuing axonal damage [25]. In our sample, no difference in hippocampal volume was detected between IDH-wildtype and IDH-mutation glioma patients.…”

“…Volume loss in brain regions remote to the site of glioma before surgery has also been found using modern imaging methods. For instance, focal glioma in the cerebral cortex leads to volumetric and diffusion alterations in distant subcortical areas, such as the caudate nucleus, putamen, and thalamus, as well as microstructural impairment of extratumoral whole-brain normal-appearing white matter [25,26]. Recently, one study reported that the hippocampus appears to be a brain region that is less prone than other regions to tumor invasion [27].…”

Asymmetric tumor‐related alterations of network‐specific intrinsic functional connectivity in glioma patients

“…All participants underwent a standardized cognitive examination, which has been described in more detail previously (Jütten et al, 2019) and included the following tests: The Verbal Learning and Memory Test (VLMT, [Helmstaedter, Lendt, & Lux, 2001]) is a list-learning paradigm, which comprises eight trials with which verbal learning and recall are assessed. Here, we focused on VLMT scores including total learning (the sum of scores for Trials 1-5, VLMT_ P Dg1-5) and consolidation performance as number of words forgotten over time (Trial 5 score-Trial 7 score, VLMT_Dg5-Dg7).…”

“…All participants underwent MRI examination on a 3T Siemens Prisma MRI scanner equipped with a standard 32-channel head coil. The detailed scanning protocol is described in a previous study (Jütten et al, 2019), and comprised the following pulse sequences: A sagittal 3D T1 magnetization-prepared rapid acquisition gradient echo…”