Multi-modal Techniques For Language Mapping In Chinese-speakers

The scientistså'Œgovernments are focusing now more than ever on the human brain and its function. The Brain Activity Map Project is announced by the Obama administration on April2013, with the goal of mapping the activity of every neuron in the human brain. Before this, European Commission also launched the Human Brain Project (HBP), which aims to simulate the worlds of human brain.Language function is unique and important to human. All mental activities are inseparable from language. Patients with brain tumors are paying more attention on the dignity and quality of life, which is currently deemed to the highest priority in the principle of brain tumor surgery. The prediction of function through classic anatomical landmarks is insufficient because of individual variability, the mass effect of the tumors and brain plasticity. Surgery may damage language cortex or network, resulting in postoperative aphasia and cognitive impairment. Thus, it is essential, during surgical removal of lesions within language areas, to identify and preserve the language cortex and subcortical tracts. However, the vast majority of previous studies on language mapping are conducted on English or other alphabetic languages. So far, there is still a lack of systematic study on the Chinese language.The present study adopted multimodality techniques (intraoperative stimulation mapping, task-based functional MRI, resting-state functional MRI, diffusion tensor imaging, intraoperative MRI) to investigate the language function on Chinese-speakers. We confirmed the reliability of intraoperative electrical stimulation mapping (the gold standard) by the functional outcome in55patients with gliomas in Part I. In Part II, we achieved technological innovation by presenting three new technologies or methods that were validated by the gold standard. In Part III, that the Chinese language maps and language networks were established by functional MRI and intraoperative cortical stimulation is promoting to achieve a theoretical innovation.Part I:Awake language mapping and3-Tesla intraoperative MRI guided volumetric resection for gliomas in language areasBoth awake surgery and intraoperative magnetic resonance imaging (iMRI) have been reported to optimize maximal safe resection of gliomas. However, there are little experiences in combining these two demanding procedures. In this study, we reported our unique experience and methodology of performing awake surgery in a movable iMRI system and quantitatively evaluate the contribution of the combination technologies on the extent of resection (EOR) and functional outcome of patients with gliomas involving language areas. From December2010through December2012,55consecutive patients who underwent awake surgery with iMRI guidance were prospectively investigated. The EOR was assessed by volumetric analysis. Language assessment was conducted before surgery and1week,1month,3months and6months respectively after surgery using the Aphasia Battery of Chinese. Awake language mapping integrated with3.0T iMRI was safely performed in all patients. An additional resection was conducted in23of55patients (41.8%) after iMRI scanning. The median EOR significantly increased from91.6%(range,45.7-99.0%) to100%(range,74%-100%) as a result of iMRI (P<0.01). Gross total resection was finally achieved in27patients (49.1%), and in8patients (29.6%), the gross total resection could be attributed to iMRI scanning. A total of22patients (40.0%) suffered from transient language deficits; however, only2(3.6%) patients had a permanent deficit during follow-up study. This study demonstrates the potential utility of combining awake craniotomy with iMRI. In addition, the functional outcome confirmed that the intraoperative language mapping is reliable and practical.Part â…¡:Technological innovation for the localization of language areasIntraoperative language mapping by the direct cortical stimulation is currently the gold standard of localization of language areas. However, it has some disadvantages.1) It can’t be applied to presurgical planning and allow neurosurgeon to visualize the relationship to lesion.2) The mapping is limited to the exposure of craniotomy.3) It required the cooperation from the patients. It isn’t suitable for children or patients with language deficits. Hence, it is urgently required to explore novel techniques or methods for localization of language areas.In this section, we proposed three novel techniques or methods based on the three different modalities (diffusion tensor imaging, task-based fMRI, resting-state fMRI).1) The arcuate fascicle fiber tracking technique is applied to localization of primary language cortex in frontal lobe and verified by the gold standard. The sensitivity was70.0%, specificity97.6%, if the bow shaped beam around1cm as a standard, the sensitivity and specificity were90.0%and96%, respectively.2) For the first time, as the best we know, we raise the concept of the "awake" intraoperative functional MRI (ai-fMRI) for the localization of real-time eloquent areas during craniotomy. The reliability of ai-fMRI was further validated using intraoperative stimulation mapping (ISM) in two patients. Comparisons between the pre-fMRI-derived localization result and the ai-fMRI derived result showed that the former was subject to a heavy brain shift and led to incorrect localization, while the latter solved that problem.3) At first, we proposed a new method to identify language components from the group independent component analysis (ICA) output in different numbers of components. Then, we applied this method to individual volunteers and patients with tumors. Results suggested that it is feasible to extract the language components from resting-state fMRI at the individual volunteer or patient. Part III:Establishment of language maps and network in Chinese-speaking patients with gliomas:A cortical electrical stimulation and fMRI studyThe mounting evidence suggests that Chinese language processing requires brain areas distinct from those used when processing the English language. However, existing studies of Chinese language processing are limited to functional neuroimaging studies. Data gathered through intraoperative stimulation of language cortex in the brain provide a unique opportunity for mapping the distribution and topographical organization of language. In this section, first of all, we obtained three task-based fMRI imaging variability maps (picture naming, verb generation, convert recitation) from15right-handed patients and one map from10right-handed healthy subjects. Then, intraoperative language mappings were obtained from55patients with gliomas. Positive sites associated with speech arrest, anomia, and alexia were categorized and used to generate cortical language maps. At last, the positive sites during the language mappings were used as the seed regions in11patients with gliomas. Resting-state correlation maps were generated to demonstrate the Chinese language network.The results suggested that1) the ventral precentral gyrus (ventral part of BA6) and the pars opercularis (BA44) play a critical role in speech production.2) By comparing stimulation maps of Chinese and English-speakers, the left middle frontal gyrus was identified as being unique to Chinese language processing.3) The language distribution of Chinese is more widely than that of Indo-European languages.4) Using only one fMRI task to identify preoperatively language areas seems to be risky; combining the fMRI tasks may be optimal.5) It’s feasible to obtain language networks from resting-state fMRI based on the cortical electrical stimulation. Conclusions This project conducted a series of studies of translational medicine about the Chinese language mapping. The main conclusions and potential application are as follows:1. We generated language maps and networks in Chinese-speakers by multi-modal techniques and investigated their characteristics, which would provide theoretical guidance for the tumor surgery adjacent to language areas.2. We proposed several feasible and reliable novel solutions for localization of language areas.3. It’s not reliable to localize the language areas using single technique because of the complexity of language. It is suggested that combining multi-modal techniques applied to verify each other should be used.The novelty of this study1. For the first time, we demonstrated and reported the combination of awake surgery and3T movable intraoperative MRI for glioma surgery adjacent to language areas.2. For the first time, we verified the effectiveness that the arcuate fascicle fiber tracking technique is applied to localization of primary language cortex in frontal lobe.3. For the first time, we raised the concept of "awake" intraoperative functional MRI (ai-fMRI) and confirmed the feasibility and reliability.4. For the first time, we proposed a new method to identify language components from the group independent component analysis (ICA) output in different numbers of components and applied this method to individual healthy subject and patient with tumor.5. For the first time, we constructed patented language maps in Chinese-speakers based on the intraoperative language mapping. 6. For the first time, we obtained language networks from resting-state fMRI based on the cortical electrical stimulation.