A Novel Technique for Region and Linguistic Specific nTMS-based DTI Fiber Tracking of Language Pathways in Brain Tumor Patients

Abstract

Navigated transcranial magnetic stimulation (nTMS) has recently been introduced as a non-invasive tool for functional mapping of cortical language areas prior to surgery. It correlates well with intraoperative neurophysiological monitoring (IONM) findings, allowing defining the best surgical strategy to preserve cortical language areas during surgery for language-eloquent tumors. Nevertheless, nTMS allows only for cortical mapping and postoperative language deficits are often caused by injury to subcortical language pathways. Nowadays, the only way to preoperatively visualize language subcortical white matter tracts consists in DTI fiber tracking (DTI-FT). However, standard DTI-FT is based on anatomical landmarks that vary interindividually and can be obscured by the presence of the tumor itself. It has been demonstrated that combining nTMS with DTI-FT allows for a more reliable visualization of the motor pathway in brain tumor patients. Nevertheless, no description about such a combination has been reported for the language network. The aim of the present study is to describe and assess the feasibility and reliability of using cortical seeding areas defined by error type-specific nTMS language mapping (nTMS-positive spots) to perform DTI-FT in patients affected by language-eloquent brain tumors. We describe a novel technique for a nTMS-based DTI-FT to visualize the complex cortico-subcortical connections of the language network. We analyzed quantitative findings, such as fractional anisotropy values and ratios, and the number of visualized connections of nTMS-positive spots with subcortical pathways, and we compared them with results obtained by using the standard DTI-FT technique. We also analyzed the functional concordance between connected cortical nTMS-positive spots and subcortical pathways, and the likelihood of connection for nTMS-positive vs. nTMS-negative cortical spots. We demonstrated, that the nTMS-based approach, especially what we call the “single-spot” strategy, is able to provide a reliable and more detailed reconstruction of the complex cortico-subcortical language network as compared to the standard DTI-FT. We believe this technique represents a beneficial new strategy for customized preoperative planning in patients affected by tumors in presumed language eloquent location, providing anatomo-functional information to plan language-preserving surgery.

Function-Based Tractography of the Language Network Correlates with Aphasia in Patients with Language-Eloquent Glioblastoma

“…The technique of nTMS has lately been used to conduct language mappings in patients suffering from language-eloquent glioma or other entities of brain tumors [13][14][15][16]. Furthermore, it has been combined with diffusion tensor imaging (DTI) derived from preoperative magnetic resonance imaging (MRI) to provide spatially resolved maps that visualize language-related structures [17][18][19][20][21][22][23][24][25]. Integration into clinical routine and the perioperative workflow is seamless, and the approach is currently regarded as a valuable adjunct to intraoperative DES [14,15].…”

“…The mere additional use of nTMS-based DTI fiber tracking (DTI FT) did not improve the identification of DES-positive language areas during awake surgery [24]. Nevertheless, the visualization of the subcortical language network becomes possible purely based on functional data by using nTMS-based DTI FT, which has shown high potential for surgical planning, resection guidance, and risk assessment in patients with language-eloquent lesions [17][18][19][20][21][22][23][24][25]. However, explorations of the differences between language-positive and language-negative nTMS mappings are still largely missing, which is one reason contributing to the lack of understanding of the comparatively low specificity of nTMS language mapping in relation to intraoperative DES.…”

Manual for clinical language tractography

“…Publications on language tractography have focused on consensus protocols in normalized space or on the functionality of the white matter tracts [ 7 , 11 , 15 , 25 , 34 , 38 ]. However, those publications have not provided standard approaches on how to obtain reliable clinical language tractography results, i.e., in pathological brains, guided by cerebral structures or without the need for normalization [ 4 , 36 , 43 ]. Studies proposing the use of noninvasive cortical mapping results to place ROIs, which are linked with language function, suffer from the limited validation of the applied technology [ 9 , 32 , 33 ].…”

Current status and potential application of navigated transcranial magnetic stimulation in neurosurgery: a literature review

“…It can visualize and calculate the electric field with its dose and orientation, as well as optimize the coil positioning continuously. The resolution of En-TMS reaches 2 mm [11,16]. At present, only the En-TMS system could be used for tumor-patient diagnostics [11][12][13][19][20][21].…”

“…In recent years, nTMS has been widely used in motor mapping, and more evidence shows that it is beneficial for patients with brain tumor. Many studies observed better outcomes and higher survival rates in brain tumor patients who use nTMS before surgery, thus expanding the initial role of nTMS as a mere preoperative planning tool [15,16].…”