FMRI-Targeted High-Angular Resolution Diffusion MR Tractography to Identify Functional Language Tracts in Healthy Controls and Glioma Patients.

Francesco Sanvito,Paola Scifo,Marco Riva,Marco Grimaldi,Antonella Iadanza,Valeria Blasi,Eduardo Caverzasi,Sofia Allegra Crespi,Maria Luisa Gorno-Tempini,Roland G Henry,Antonella Castellano,Sara Cirillo,Lorenzo Bello,Guglielmo Puglisi,Kesshi M Jordan,Andrea Falini,Alessandra Casarotti,Antonella Leonetti

doi:10.3389/fnins.2020.00225

Abstract

BackgroundMR Tractography enables non-invasive preoperative depiction of language subcortical tracts, which is crucial for the presurgical work-up of brain tumors; however, it cannot evaluate the exact function of the fibers.PurposeA systematic pipeline was developed to combine tractography reconstruction of language fiber bundles, based on anatomical landmarks (Anatomical-T), with language fMRI cortical activations. A fMRI-targeted Tractography (fMRI-T) was thus obtained, depicting the subsets of the anatomical tracts whose endpoints are located inside a fMRI activation. We hypothesized that fMRI-T could provide additional functional information regarding the subcortical structures, better reflecting the eloquent white matter structures identified intraoperatively.MethodsBoth Anatomical-T and fMRI-T of language fiber tracts were performed on 16 controls and preoperatively on 16 patients with left-hemisphere brain tumors, using a q-ball residual bootstrap algorithm based on High Angular Resolution Diffusion Imaging (HARDI) datasets (b = 3000 s/mm2; 60 directions); fMRI ROIs were obtained using picture naming, verbal fluency, and auditory verb generation tasks. In healthy controls, normalized MNI atlases of fMRI-T and Anatomical-T were obtained. In patients, the surgical resection of the tumor was pursued by identifying eloquent structures with intraoperative direct electrical stimulation mapping and extending surgery to the functional boundaries. Post-surgical MRI allowed to identify Anatomical-T and fMRI-T non-eloquent portions removed during the procedure.ResultsMNI Atlases showed that fMRI-T is a subset of Anatomical-T, and that different task-specific fMRI-T involve both shared subsets and task-specific subsets – e.g., verbal fluency fMRI-T strongly involves dorsal frontal tracts, consistently with the phonogical-articulatory features of this task. A quantitative analysis in patients revealed that Anatomical-T removed portions of AF-SLF and IFOF were significantly greater than verbal fluency fMRI-T ones, suggesting that fMRI-T is a more specific approach. In addition, qualitative analyses showed that fMRI-T AF-SLF and IFOF predict the exact functional limits of resection with increased specificity when compared to Anatomical-T counterparts, especially the superior frontal portion of IFOF, in a subcohort of patients.ConclusionThese results suggest that performing fMRI-T in addition to the ‘classic’ Anatomical-T may be useful in a preoperative setting to identify the ‘high-risk subsets’ that should be spared during the surgical procedure.

Highlights

The accurate identification of eloquent fiber tracts, such as language bundles, is a crucial step in the surgical work-up of brain tumors
Their generation was based on a two-step pipeline: the first step consisted in obtaining a functional MRI (fMRI)-target-Region of Interest (ROI) that reflected the subject-specific task-specific activation areas; the second step consisted in generating fMRI-targeted Tractography (fMRI-T) tracts representing the subsets of the Anatomical-T tracts whose endpoints are located inside the fMRI-target-ROI
A manual extension of the fMRI-ROI was performed exclusively when the endpoints of some streamlines were located within 3 voxels outside the fMRI-ROI and in the same anatomical area – a similar ROI-extension correction is reported in other fMRI-based Tractography studies (Upadhyay et al, 2007; Zhu et al, 2014)

Summary

Introduction

The accurate identification of eloquent fiber tracts, such as language bundles, is a crucial step in the surgical work-up of brain tumors. MR Tractography enables the in vivo non-invasive depiction of subcortical fascicles and it has rapidly become fundamental in the presurgical assessment of brain tumors (Bello et al, 2010; Riva et al, 2011; Castellano et al, 2012; Ulmer et al, 2014), in order to evaluate the displacement or modifications of the eloquent bundles before performing brain surgery (Bello et al, 2008; Bizzi, 2009; Essayed et al, 2017), to predict the extent of resection (Castellano et al, 2012), and to Abbreviations: AF, Arcuate Fasciculus; Anatomical-T, Anatomical Tractography; AVG, Auditory Verb Generation; DES, Direct Electrical Stimulation; ExC, External/Extreme Capsule; FAT, Frontal Aslant Tract; fMRI-T, fMRI-targeted Tractography; IFOF, Inferior Fronto-Occipital Fasciculus; ILF, Inferior Longitudinal Fasciculus; MNI, Montreal Neurological Institute; PN, Picture Naming; ROI, Region of Interest; SLF, Superior Longitudinal Fasciculus; SLF-II, II component of SLF; SLF-III, III component of SLF; SLF-tp, temporo-parietal (or vertical) component of SLF; UF, Uncinate Fasciculus; VF, Verbal Fluency. We hypothesized that fMRI-T could provide additional functional information regarding the subcortical structures, better reflecting the eloquent white matter structures identified intraoperatively

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