Sebastian Ille, Nico Sollmann, Theresa Hauck, Stefanie Maurer, Noriko Tanigawa, Thomas Obermueller, Chiara Negwer, Doris Droese, Claus Zimmer, Bernhard Meyer, Florian Ringel and Sandro M. Krieg
Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods.
The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery.
The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%.
In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.
Chiara Negwer, Nico Sollmann, Sebastian Ille, Theresa Hauck, Stefanie Maurer, Jan S. Kirschke, Florian Ringel, Bernhard Meyer and Sandro M. Krieg
Diffusion tensor imaging (DTI) fiber tracking (FT) has been widely used in glioma surgery in recent years. It can provide helpful information about subcortical structures, especially in patients with eloquent space-occupying lesions. This study compared the newly developed navigated transcranial magnetic stimulation (nTMS)-based DTI FT of language pathways with the most reproducible protocol for language pathway tractography, using cubic regions of interest (ROIs) for the arcuate fascicle.
Thirty-seven patients with left-sided perisylvian lesions underwent language mapping by repetitive nTMS. DTI FT was performed using the cubic ROIs–based protocol and the authors' nTMS-based DTI FT approach. The same minimal fiber length and fractional anisotropy were chosen (50 mm and 0.2, respectively). Both protocols were performed with standard clinical tractography software.
Both methods visualized language-related fiber tracts (i.e., corticonuclear tract, arcuate fascicle, uncinate fascicle, superior longitudinal fascicle, inferior longitudinal fascicle, arcuate fibers, commissural fibers, corticothalamic fibers, and frontooccipital fascicle) in all 37 patients. Using the cubic ROIs-based protocol, 39.9% of these language-related fiber tracts were detected in the examined patients, as opposed to 76.0% when performing nTMS-based DTI FT. For specifically tracking the arcuate fascicle, however, the cubic ROIs-based approach showed better results (97.3% vs 75.7% with nTMS-based DTI FT).
The cubic ROIs-based protocol was designed for arcuate fascicle tractography, and this study shows that it is still useful for this intention. However, superior results were obtained using the nTMS-based DTI FT for visualization of other language-related fiber tracts.
Sebastian Ille, Nico Sollmann, Theresa Hauck, Stefanie Maurer, Noriko Tanigawa, Thomas Obermueller, Chiara Negwer, Doris Droese, Tobias Boeckh-Behrens, Bernhard Meyer, Florian Ringel and Sandro M. Krieg
Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions.
Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions.
The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%).
Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.
Nico Sollmann, Chiara Negwer, Lorena Tussis, Theresa Hauck, Sebastian Ille, Stefanie Maurer, Katrin Giglhuber, Jan S. Bauer, Florian Ringel, Bernhard Meyer and Sandro M. Krieg
Resection of brain tumors in language-eloquent areas entails the risk of postoperative aphasia. It has been demonstrated via navigated transcranial magnetic stimulation (nTMS) that language function can partially shift to the unaffected hemisphere due to tumor-induced plasticity. Therefore, this study was designed to evaluate whether interhemispheric connectivity (IC) detected by nTMS-based diffusion tensor imaging–fiber tracking (DTI-FT) can be used to predict surgery-related aphasia in patients with brain tumors.
Thirty-eight patients with left-sided perisylvian brain lesions underwent cortical language mapping of both hemispheres by nTMS prior to awake surgery. Then, nTMS-based DTI-FT was conducted with a fractional anisotropy (FA) of 0.01 and 0.2 to visualize nTMS-based IC. Receiver operating characteristics were calculated for the prediction of a postoperative (irrespective of the preoperative state) and a new surgery-related aphasia by the presence of detectable IC.
Language mapping by nTMS was possible in all patients. Seventeen patients (44.7%) suffered from surgery-related worsening of language performance (transient aphasia according to 3-month follow-up in 16 subjects [42.1%]; new permanent aphasia according to 3-month follow-up in 1 patient [2.6%]). Regarding the correlation of aphasia to nTMS-based IC, statistically significant differences were revealed for both evaluated FA values. However, better results were observed for tractography with an FA of 0.2, which led to a specificity of 93% (postoperative aphasia) and 90% (surgery-related aphasia). For postoperative aphasia, the corresponding OR was 0.1282 (95% CI 0.0143–1.1520), and for surgery-related aphasia the OR was 0.1184 (95% CI 0.0208–0.6754).
According to these results, IC detected by preoperative nTMS-based DTI-FT might be regarded as a risk factor for surgery-related aphasia, with a specificity of up to 93%. However, because the majority of enrolled patients suffered from transient aphasia postoperatively, it has to be evaluated whether this approach distinctly leads to similar results among patients with permanent language deficits. Despite this restriction, this approach might contribute to individualized patient consultation prior to tumor resection in clinical practice.