Lesion-Function Analysis from Multimodal Imaging and Normative Brain Atlases for Prediction of Cognitive Deficits in Glioma Patients.

Martin Kocher,Karl-Josef Langen,Gereon R Fink,Roland Goldbrunner,Christiane Jockwitz,Christian Filss,Svenja Caspers,Gabriele Stoffels,Philipp Lohmann,Felix M Mottaghy,Nadim J Shah,Norbert Galldiks,Maximilian I Ruge,Carolin Weiss Lucas

doi:10.3390/cancers13102373

Abstract

Simple SummaryThis prospective cross-sectional study utilized standard structural MR imaging and amino acid PET in conjunction with brain atlases of gray matter functional regions and white matter tracts, and elastic registration techniques to estimate the influence of the type and location of treatment-related brain damage or recurrent tumors on cognitive functioning in a group of well-doing WHO Grade III/IV glioma patients at follow-up after treatment. The negative impact of T2/FLAIR hyperintensities, supposed to be mainly caused by radiotherapy, on cognitive performance far exceeded that of surgical brain defects or recurrent tumors. The affection of functional nodes and fiber tracts of the left hemisphere and especially of the left temporal lobe by T2/FLAIR hyperintensities was highly correlated with verbal episodic memory dysfunction. These observations imply that radiotherapy for gliomas of the left hemisphere should be individually tailored by means of publicly available brain atlases and registration techniques.Cognitive deficits are common in glioma patients following multimodality therapy, but the relative impact of different types and locations of treatment-related brain damage and recurrent tumors on cognition is not well understood. In 121 WHO Grade III/IV glioma patients, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine FET-PET, and neuropsychological testing were performed at a median interval of 14 months (range, 1–214 months) after therapy initiation. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and FET-PET positive tumor sites were semi-automatically segmented and elastically registered to a normative, resting state (RS) fMRI-based functional cortical network atlas and to the JHU atlas of white matter (WM) tracts, and their influence on cognitive test scores relative to a cohort of matched healthy subjects was assessed. T2/FLAIR hyperintensities presumably caused by radiation therapy covered more extensive brain areas than the other lesion types and significantly impaired cognitive performance in many domains when affecting left-hemispheric RS-nodes and WM-tracts as opposed to brain tissue damage caused by resection or recurrent tumors. Verbal episodic memory proved to be especially vulnerable to T2/FLAIR abnormalities affecting the nodes and tracts of the left temporal lobe. In order to improve radiotherapy planning, publicly available brain atlases, in conjunction with elastic registration techniques, should be used, similar to neuronavigation in neurosurgery.

Highlights

Patients suffering from WHO Grade III/IV glioma typically undergo an extended sequence of therapeutic interventions, including repeated tumor resection, irradiation, re-irradiation, and multiple courses of chemotherapy or targeted molecular therapy [1,2,3].While tumor resection carries the risk of immediate damage to functional gray matter and the connecting tracts, radiotherapy is assumed to induce delayed damage, predominantly to the irradiated white matter [4]; chemotherapy may cause diffuse damage in widespread regions of the brain [5]
A weak influence was observed for glioma grading and molecular subtype
In the present analysis performed in WHO Grade III/IV glioma patients following multimodality therapy, T2/FLAIR abnormalities rather than brain tissue defects due to neurosurgical resection or recurrent tumors most severely correlated with cognitive outcomes

Summary

Introduction

While tumor resection carries the risk of immediate damage to functional gray matter and the connecting tracts, radiotherapy is assumed to induce delayed damage, predominantly to the irradiated white matter [4]; chemotherapy may cause diffuse damage in widespread regions of the brain [5]. According to current brain function theories, performance in higher cognitive domains depends on the specialized function of cortical regions and their interaction in multiple networks [16]. A parcellation of the cortex into functionally connected nodes belonging to specified networks of known cognitive function was derived from restingstate fMRI data [17,18]. A widely recognized atlas of the central white matter tracts was developed by the Johns Hopkins University [19]

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