Associations between clinical outcome and tractography based on navigated transcranial magnetic stimulation in patients with language-eloquent brain lesions

Restricted access


Navigated transcranial magnetic stimulation (nTMS) in combination with diffusion tensor imaging fiber tracking (DTI FT) is increasingly used to locate subcortical language-related pathways. The aim of this study was to establish nTMS-based DTI FT for preoperative risk stratification by evaluating associations between lesion-to-tract distances (LTDs) and aphasia and by determining a cut-off LTD value to prevent surgery-related permanent aphasia.


Fifty patients with left-hemispheric, language-eloquent brain tumors underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by tumor resection. nTMS-based DTI FT was performed with a predefined fractional anisotropy (FA) of 0.10, 0.15, 50% of the individual FA threshold (FAT), and 75% FAT (minimum fiber length [FL]: 100 mm). The arcuate fascicle (AF), superior longitudinal fascicle (SLF), inferior longitudinal fascicle (ILF), uncinate fascicle (UC), and frontooccipital fascicle (FoF) were identified in nTMS-based tractography, and minimum LTDs were measured between the lesion and the AF and between the lesion and the closest other subcortical language-related pathway (SLF, ILF, UC, or FoF). LTDs were then associated with the level of aphasia (no/transient or permanent surgery-related aphasia, according to follow-up examinations).


A significant difference in LTDs was observed between patients with no or only surgery-related transient impairment and those who developed surgery-related permanent aphasia with regard to the AF (FA = 0.10, p = 0.0321; FA = 0.15, p = 0.0143; FA = 50% FAT, p = 0.0106) as well as the closest other subcortical language-related pathway (FA = 0.10, p = 0.0182; FA = 0.15, p = 0.0200; FA = 50% FAT, p = 0.0077). Patients with surgery-related permanent aphasia showed the lowest LTDs in relation to these tracts. Thus, LTDs of ≥ 8 mm (AF) and ≥ 11 mm (SLF, ILF, UC, or FoF) were determined as cut-off values for surgery-related permanent aphasia.


nTMS-based DTI FT of subcortical language-related pathways seems suitable for risk stratification and prediction in patients suffering from language-eloquent brain tumors. Thus, the current role of nTMS-based DTI FT might be expanded, going beyond the level of being a mere tool for surgical planning and resection guidance.

ABBREVIATIONS AF = arcuate fascicle; CST = corticospinal tract; DES = direct electrical stimulation; DTI = diffusion tensor imaging; DTI FT = diffusion tensor imaging fiber tracking; FA = fractional anisotropy; FAT = fractional anisotropy threshold; FL = fiber length; FLAIR = fluid attenuated inversion recovery; FoF = frontooccipital fascicle; ILF = inferior longitudinal fascicle; IONM = intraoperative neuromonitoring; LAD = lesion-to-activation distance; LED = lesion-to-eloquence distance; LTD = lesion-to-tract distance; MRI = magnetic resonance imaging; mRS = modified Rankin Scale; nTMS = navigated transcranial magnetic stimulation; rMT = resting motor threshold; ROI = region of interest; rs = Spearman correlation coefficient; SD = standard deviation; SLF = superior longitudinal fascicle; UC = uncinate fascicle.

Article Information

Correspondence Sandro M. Krieg: Technische Universität München, Munich, Germany.

INCLUDE WHEN CITING Published online March 15, 2019; DOI: 10.3171/2018.12.JNS182988.

N.S. and A.F. contributed equally to this work.

Disclosures NS reports receipt of honoraria from Nexstim Plc. SK reports consultant relationships with Nexstim Plc and Spineart Deutschland GmbH and receipt of honoraria from Medtronic and Carl Zeiss Meditec. SK and BM report receipt of research grants from and consultant relationships with Brainlab AG. BM reports receipt of honoraria, consulting fees, and research grants from Medtronic, Icotec ag, and Relievant Medsystems Inc.; honoraria and research grants from Ulrich Medical; honoraria and consulting fees from Spineart Deutschland GmbH and DePuy Synthes; and royalties from Spineart Deutschland GmbH. However, all authors declare that they have no conflict of interest regarding the materials used or the results presented in this study.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Measurement of the lesion-to-tract distance (LTD) in relation to the superior longitudinal fascicle (SLF). This illustrative patient case depicts LTD measurement in relation to the SLF, which was visually identified in tractography based on language maps derived from nTMS. Subcortical language-related pathways are shown in purple, the CST is highlighted in yellow. During LTD measurements, all planes were considered, with representative sagittal and coronal images of the FLAIR and contrast-enhanced T1-weighted gradient echo sequences being shown in this figure. In this case (involving a 27-year-old woman with a left-hemispheric WHO grade II glioma), the minimum LTD was 7.63 mm. Figure is available in color online only.

  • View in gallery

    Measurement of the lesion-to-tract distance (LTD) in relation to the frontooccipital fascicle (FoF). This illustrative patient case depicts LTD measurement in relation to the FoF according to visual inspection of tractography based on language maps derived from nTMS. Subcortical language-related pathways are shown in purple, the CST is highlighted in yellow. During LTD measurements, all planes were considered, with representative coronal and axial images of the contrast-enhanced T1-weighted gradient echo sequence being shown in this figure. In this illustrative case (involving a 37-year-old woman with a left-hemispheric WHO grade III glioma), the minimum LTD was 0.0 mm because the tumor borders showed direct contact to the FoF (red circle). Figure is available in color online only.


  • 1

    Abhinav KYeh FCPathak SSuski VLacomis DFriedlander RM: Advanced diffusion MRI fiber tracking in neurosurgical and neurodegenerative disorders and neuroanatomical studies: a review. Biochim Biophys Acta 1842:228622972014

  • 2

    Axer HKlingner CMPrescher A: Fiber anatomy of dorsal and ventral language streams. Brain Lang 127:1922042013

  • 3

    Bailey PDZacà DBasha MMAgarwal SGujar SKSair HI: Presurgical fMRI and DTI for the prediction of perioperative motor and language deficits in primary or metastatic brain lesions. J Neuroimaging 25:7767842015

  • 4

    Berman JIBerger MSChung SWNagarajan SSHenry RG: Accuracy of diffusion tensor magnetic resonance imaging tractography assessed using intraoperative subcortical stimulation mapping and magnetic source imaging. J Neurosurg 107:4884942007

  • 5

    Catani MThiebaut de Schotten M: A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex 44:110511322008

  • 6

    Caverzasi EHervey-Jumper SLJordan KMLobach IVLi JPanara V: Identifying preoperative language tracts and predicting postoperative functional recovery using HARDI q-ball fiber tractography in patients with gliomas. J Neurosurg 125:33452016

  • 7

    Chang EFRaygor KPBerger MS: Contemporary model of language organization: an overview for neurosurgeons. J Neurosurg 122:2502612015

  • 8

    Duffau H: Diffusion tensor imaging is a research and educational tool, but not yet a clinical tool. World Neurosurg 82:e43e452014

  • 9

    Duffau HMandonnet E: The “onco-functional balance” in surgery for diffuse low-grade glioma: integrating the extent of resection with quality of life. Acta Neurochir (Wien) 155:9519572013

  • 10

    Fraga de Abreu VHPeck KKPetrovich-Brennan NMWoo KMHolodny AI: Brain tumors: the influence of tumor type and routine MR imaging characteristics at BOLD functional MR imaging in the primary motor gyrus. Radiology 281:8768832016

  • 11

    Frey DStrack VWiener EJussen DVajkoczy PPicht T: A new approach for corticospinal tract reconstruction based on navigated transcranial stimulation and standardized fractional anisotropy values. Neuroimage 62:160016092012

  • 12

    Gierhan SM: Connections for auditory language in the human brain. Brain Lang 127:2052212013

  • 13

    Hervey-Jumper SLBerger MS: Maximizing safe resection of low- and high-grade glioma. J Neurooncol 130:2692822016

  • 14

    Hervey-Jumper SLBerger MS: Technical nuances of awake brain tumor surgery and the role of maximum safe resection. J Neurosurg Sci 59:3513602015

  • 15

    Hervey-Jumper SLLi JLau DMolinaro AMPerry DWMeng L: Awake craniotomy to maximize glioma resection: methods and technical nuances over a 27-year period. J Neurosurg 123:3253392015

  • 16

    Holodny AISchulder MLiu WCWolko JMaldjian JAKalnin AJ: The effect of brain tumors on BOLD functional MR imaging activation in the adjacent motor cortex: implications for image-guided neurosurgery. AJNR Am J Neuroradiol 21:141514222000

  • 17

    Huber WPoeck KWillmes K: The Aachen Aphasia Test. Adv Neurol 42:2913031984

  • 18

    Jiao YLin FWu JLi HWang LJin Z: A supplementary grading scale combining lesion-to-eloquence distance for predicting surgical outcomes of patients with brain arteriovenous malformations. J Neurosurg 128:5305402018

  • 19

    Krieg SMLioumis PMäkelä JPWilenius JKarhu JHannula H: Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report. Acta Neurochir (Wien) 159:118711952017

  • 20

    Krieg SMSollmann NTanigawa NFoerschler AMeyer BRingel F: Cortical distribution of speech and language errors investigated by visual object naming and navigated transcranial magnetic stimulation. Brain Struct Funct 221:225922862016

  • 21

    Kuhnt DBauer MHEgger JRichter MKapur TSommer J: Fiber tractography based on diffusion tensor imaging compared with high-angular-resolution diffusion imaging with compressed sensing: initial experience. Neurosurgery 72 (Suppl 1):1651752013

  • 22

    Langen KJGalldiks NHattingen EShah NJ: Advances in neuro-oncology imaging. Nat Rev Neurol 13:2792892017

  • 23

    Le Bihan DPoupon CAmadon ALethimonnier F: Artifacts and pitfalls in diffusion MRI. J Magn Reson Imaging 24:4784882006

  • 24

    Lioumis PZhdanov AMäkelä NLehtinen HWilenius JNeuvonen T: A novel approach for documenting naming errors induced by navigated transcranial magnetic stimulation. J Neurosci Methods 204:3493542012

  • 25

    Meyer EJGaggl WGilloon BSwan BGreenstein MVoss J: The impact of intracranial tumor proximity to white matter tracts on morbidity and mortality: a retrospective diffusion tensor imaging study. Neurosurgery 80:1932002017

  • 26

    Negwer CBeurskens ESollmann NMaurer SIlle SGiglhuber K: Loss of subcortical language pathways correlates with surgery-related aphasia in patients with brain tumor: an investigation via repetitive navigated transcranial magnetic stimulation-based diffusion tensor imaging fiber tracking. World Neurosurg 111:e806e8182018

  • 27

    Negwer CIlle SHauck TSollmann NMaurer SKirschke JS: Visualization of subcortical language pathways by diffusion tensor imaging fiber tracking based on rTMS language mapping. Brain Imaging Behav 11:8999142017

  • 28

    Ottenhausen MKrieg SMMeyer BRingel F: Functional preoperative and intraoperative mapping and monitoring: increasing safety and efficacy in glioma surgery. Neurosurg Focus 38(1):E32015

  • 29

    Picht TKrieg SMSollmann NRösler JNiraula BNeuvonen T: A comparison of language mapping by preoperative navigated transcranial magnetic stimulation and direct cortical stimulation during awake surgery. Neurosurgery 72:8088192013

  • 30

    Raffa GBährend ISchneider HFaust KGermanò AVajkoczy P: A novel technique for region and linguistic specific nTMS-based DTI fiber tracking of language pathways in brain tumor patients. Front Neurosci 10:5522016

  • 31

    Raffa GConti AScibilia ASindorio CQuattropani MCVisocchi M: Functional reconstruction of motor and language pathways based on navigated transcranial magnetic stimulation and DTI fiber tracking for the preoperative planning of low grade glioma surgery: a new tool for preservation and restoration of eloquent networks. Acta Neurochir Suppl 124:2512612017

  • 32

    Rosenstock TGrittner UAcker GSchwarzer VKulchytska NVajkoczy P: Risk stratification in motor area-related glioma surgery based on navigated transcranial magnetic stimulation data. J Neurosurg 126:122712372017

  • 33

    Ruohonen JKarhu J: Navigated transcranial magnetic stimulation. Neurophysiol Clin 40:7172010

  • 34

    Sanai NBerger MS: Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:264266753–764 2008

  • 35

    Sanai NBerger MS: Mapping the horizon: techniques to optimize tumor resection before and during surgery. Clin Neurosurg 55:14192008

  • 36

    Sollmann NGiglhuber KTussis LMeyer BRingel FKrieg SM: nTMS-based DTI fiber tracking for language pathways correlates with language function and aphasia—a case report. Clin Neurol Neurosurg 136:25282015

  • 37

    Sollmann NIlle SHauck TMaurer SNegwer CZimmer C: The impact of preoperative language mapping by repetitive navigated transcranial magnetic stimulation on the clinical course of brain tumor patients. BMC Cancer 15:2612015

  • 38

    Sollmann NKelm AIlle SSchröder AZimmer CRingel F: Setup presentation and clinical outcome analysis of treating highly language-eloquent gliomas via preoperative navigated transcranial magnetic stimulation and tractography. Neurosurg Focus 44(6):E22018

  • 39

    Sollmann NNegwer CIlle SMaurer SHauck TKirschke JS: Feasibility of nTMS-based DTI fiber tracking of language pathways in neurosurgical patients using a fractional anisotropy threshold. J Neurosci Methods 267:45542016

  • 40

    Sollmann NPicht TMäkelä JPMeyer BRingel FKrieg SM: Navigated transcranial magnetic stimulation for preoperative language mapping in a patient with a left frontoopercular glioblastoma. J Neurosurg 118:1751792013

  • 41

    Sollmann NWildschuetz NKelm AConway NMoser TBulubas L: Associations between clinical outcome and navigated transcranial magnetic stimulation characteristics in patients with motor-eloquent brain lesions: a combined navigated transcranial magnetic stimulation-diffusion tensor imaging fiber tracking approach. J Neurosurg 128:8008102018

  • 42

    Szelényi ABello LDuffau HFava EFeigl GCGalanda M: Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice. Neurosurg Focus 28(2):E72010

  • 43

    Talacchi ASantini BCasagrande FAlessandrini FZoccatelli GSquintani GM: Awake surgery between art and science. Part I: clinical and operative settings. Funct Neurol 28:2052212013

  • 44

    Talacchi ASantini BCasartelli MMonti ACapasso RMiceli G: Awake surgery between art and science. Part II: language and cognitive mapping. Funct Neurol 28:2232392013

  • 45

    Ulmer JLSalvan CVMueller WMKrouwer HGStroe GOAralasmak A: The role of diffusion tensor imaging in establishing the proximity of tumor borders to functional brain systems: implications for preoperative risk assessments and postoperative outcomes. Technol Cancer Res Treat 3:5675762004




All Time Past Year Past 30 Days
Abstract Views 514 514 131
Full Text Views 89 89 35
PDF Downloads 52 52 25
EPUB Downloads 0 0 0


Google Scholar