Risk Assessment by Presurgical Tractography Using Navigated TMS Maps in Patients with Highly Motor- or Language-Eloquent Brain Tumors

Abstract

Patients with functionally eloquent brain lesions are at risk of functional decline in the course of resection. Given tumor-related plastic reshaping and reallocation of function, individual data are needed for patient counseling and risk assessment prior to surgery. This study evaluates the utility of mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT) for individual risk evaluation of surgery-related decline of motor or language function in the clinical setting. In total, 250 preoperative nTMS mappings (100 language and 150 motor mappings) derived from 216 patients (mean age: 57.0 ± 15.5 years, 58.8% males; glioma World Health Organization (WHO) grade I & II: 4.2%, glioma WHO grade III & IV: 83.4%, arteriovenous malformations: 1.9%, cavernoma: 2.3%, metastasis: 8.2%) were included. Deterministic tractography based on nTMS motor or language maps as seed regions was performed with 25%, 50%, and 75% of the individual fractional anisotropy threshold (FAT). Lesion-to-tract distances (LTDs) were measured between the tumor mass and the corticospinal tract (CST), arcuate fascicle (AF), or other closest language-related tracts. LTDs were compared between patients and correlated to the functional status (no/transient/permanent surgery-related paresis or aphasia). Significant differences were found between patients with no or transient surgery-related deficits and patients with permanent surgery-related deficits regarding LTDs in relation to the CST (p < 0.0001), AF (p ≤ 0.0491), or other closest language-related tracts (p ≤ 0.0435). The cut-off values for surgery-related paresis or aphasia were ≤ 12 mm (LTD—CST) and ≤ 16 mm (LTD—AF) or ≤25 mm (LTD—other closest language-related tract), respectively. Moreover, there were significant associations between the status of surgery-related deficits and the LTD when considering the CST (range r: −0.3994 to −0.3910, p < 0.0001) or AF (range r: −0.2918 to −0.2592, p = 0.0135 and p = 0.0473 for 25% and 50% FAT). In conclusion, this is the largest study evaluating the application of both preoperative functional mapping and function-based tractography for motor and language function for risk stratification in patients with functionally eloquent tumors. The LTD may qualify as a viable marker that can be seamlessly assessed in the clinical neurooncological setup.

Short-Interval Intracortical Facilitation Improves Efficacy in nTMS Motor Mapping of Lower Extremity Muscle Representations in Patients with Supra-Tentorial Brain Tumors

“…As for motor mapping, the two investigators performed nTMS-based DTI FT independently and were blinded to each other's tractography results. The motor-positive stimulation points were fused with the MRI dataset of the respective patient, followed by definition of the motor-positive stimulation points as one object, which was transferred into a region of interest (ROI) by adding rims of 2 mm to each point [8][9][10]. In the ipsilateral brain stem, a manually drawn polygonal, second ROI was generated to subsequently track fibers connecting these two ROIs [8][9][10].…”

“…The motor-positive stimulation points were fused with the MRI dataset of the respective patient, followed by definition of the motor-positive stimulation points as one object, which was transferred into a region of interest (ROI) by adding rims of 2 mm to each point [8][9][10]. In the ipsilateral brain stem, a manually drawn polygonal, second ROI was generated to subsequently track fibers connecting these two ROIs [8][9][10]. CST tracking was then achieved with predefined fractional anisotropy (FA) values of 0.1 and 0.15, combined with a minimum fiber length of 100 mm [8,40].…”

“…It has repeatedly demonstrated high accuracy, with distances between motor hotspots derived from nTMS and intraoperative direct electrical stimulation (DES)-the gold-standard method for functional mapping-ranging within the inaccuracy of the neuronavigation system [1][2][3][4]. Furthermore, the seamless combination of nTMS motor maps with diffusion tensor imaging (DTI) and intraoperative neuronavigation environments enables additional tractography of the corticospinal tract (CST) purely based on functional data [6][7][8][9][10][11]. Hence, detailed presurgical assessment of the patient's individual motor system becomes feasible and has shown potential to improve surgical outcome [12][13][14][15].…”

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.…”