I. Background The diagnosis and treatment of human tumors is still a challenge, and when it occurs in the still unknown central nervous system (CNS), it undoubtedly adds to the confusion and complexity. Nevertheless, the development of medical theory and technology, the intersection and integration of different disciplines, the pioneering work of pioneers and the efforts of medical colleagues have made the diagnosis and treatment of CNS tumors a highlight of modern medicine. Starting from the systematic classification of CNS tumors by Cushing and Bailey (1926) based on the embryonic residual theory, the WHO-led classification of CNS tumor pathology has been updated to the fourth edition (2007), which not only precisely annotates the histopathological features of CNS tumors, but also summarizes the geneticprofile of brain tumor occurrence and development. Starting from Dandy’s invention of pneumoencephalography (1918) and Moniz’s cerebral angiography (1927), which inferred brain tumors from indirect images, today’s diagnostic imaging has advanced from the identification of tumor types to the attempt to diagnose tumor subtypes and characterize tumor biology, and to visualize the relationship between tumors and white matter conduction tracts, the localization of cortical functional areas, and the molecular and metabolic information of tumors. Since Macewen successfully performed brain tumor surgery with the naked eye in Glasgow, England (1897), today’s microsurgery, neuroendoscopy, and image-guided techniques have broken through the confines of naked eye surgery and promoted the concept of “maximum tumor resection with neurological protection”. In the clinical management of CNS tumors, the question of whether there is still an opportunity for aggressive surgical intervention is the first question to be answered, especially in malignant tumors, where surgical resection is often the initial and main step of comprehensive treatment. The literature reports that in patients with untreated or recurrent glioblastoma, removal of 98% or more of the tumor tissue is a significant predictor of survival; removal of at least 78% of the tumor load is required to improve the patient’s surgical outcome. When we describe how much tumor to remove to benefit patient survival, we focus more on the structural relationship between the tumor and the brain and the anatomical resection of the tumor. Based on the anatomical details of the tumor itself and with the brain structures as revealed by conventional images such as cranial CT and MRI, the surgical goal of maximum tumor resection can be basically achieved with the help of microsurgical techniques. However, malignant CNS tumors often diffusely and infiltratively involve functional areas and deep structures of the brain, and intraoperative “neurological protection” is highly uncertain based on the above-mentioned techniques and the surgeon’s personal experience alone. Therefore, reducing the extent of tumor resection in order to maintain postoperative neurological function has become a “compromise” for neurosurgeons. Broadly speaking, eloquentareas are all cortical areas (including language, motor, visual, and sensory areas), thalamus and basal ganglia, brainstem, and deep cerebellar nuclei that are essential to maintain overall human function. There are three main difficulties in the protection of brain function during CNS tumor surgery: the still unknown domain of brain function, the existence of individual physiological differences in functional brain areas, and the pathological interference of CNS tumors with the location of functional brain areas. Let us take language function as an example and analyze why we do not yet fully understand brain function. In fact, the word “eloquent” is borrowed from the Latin word “eloquens”, the English equivalent of which is “fluent”, i.e., the fluency of language. fluent. In a narrow sense, “eloquentareas” refers to the brain areas that allow for fluent language expression. Classical theory suggests that language centers are located in Broca’s area, Wernicke’s area, and the angular and supramarginal gyri of the dominant hemisphere. The coordination of these brain areas in the network between auditory and semantic correspondence, language comprehension, lexical expression and articulatory control constitutes the Wernicke-Lichtheim-Geschwind model. However, this model cannot explain a part of the complex aphasia, and the elaboration of syntax, phonology and semantics is insufficient. It has been found that Broca’s area and Wernicke’s area are not single-function brain areas, in which there may be a finer division of functions; other brain areas such as the basal ganglia and even the right hemisphere are involved in language processing; the superior temporal gyrus is a functionally active area, and the right temporal lobe has an important role at least in speech comprehension. Thus, there are still many unknowns to be answered in our understanding of human language function. In addition to physiological individual differences in functional brain areas, in pathological situations, tumors can distort, displace, or destroy functional brain structures or remodel neurological functions. Therefore, intraoperative reliance on traditional anatomical landmarks to locate the functional cortex is not reliable, and precise spatial localization of deep brain lesions and their relationship to white matter fibers is difficult, which affects the outcome of surgical resection of tumors involving functional brain areas and deep brain areas. The advent of image-guided and neurofunctional-guided neurosurgery supports a shift in the concept of CNS tumor surgery from “operating on tumors in brain tissue” to “operating on brain tissue with tumorigenic lesions”. “The above expressions are not at all sequential. The above statement is not a game of sequences at all, but requires solving the following technical challenges: How to assess the function of the brain area with tumor growth? How to trace the white matter conduction bundle alignment around the tumor and the nerve fiber connections between the functional brain regions? How to achieve real-time intraoperative guidance? In the clinical practice of CNS tumor surgical treatment, the neurosurgery department of the hospital has taken the lead in practicing the concept of transformation surgery. Preoperative functional assessment of tumor-involved brain regions: (1) task-based functional MRI (task-based functional MRI) is based on the magnetic susceptibility effect of deoxygenated hemoglobin, and during MRI examination, subjects complete corresponding functional tasks (motor, sensory, emotional and cognitive brain activation tests), which is similar to bloodoxygenleveldependent functional MRI (bloodoxygenleveldependent functional MRI). The baseline signal of bloodoxygenleveldependentfunctionalMRI (BOLD-fMRI) is compared with the baseline signal of bloodoxygenleveldependentfunctionalMRI (BOLD-fMRI), and the functions of motor, sensory, language and visual cortical areas are analyzed and identified on the MRI image. (2) Resting-state fMRI is to measure the spontaneous low-frequency fluctuations of BOLD signal in the resting state without stimulation or task activation, to capture the spontaneous neuronal activity of the brain, and to study the synchronous activation of different brain regions to reflect the functional architecture of the brain. Resting-state fMRI can be used for localization of cortical functional areas in patients who cannot cooperate with task-state MRI, such as pediatric patients, patients with psychiatric symptoms or pharmacological sedation, and patients with neurological deficits such as limbic palsy or aphasia. Preliminary studies of clinical applications have confirmed that resting-state fMRI acquires motor cortices with similar results to task-state fMRI and direct electrical cortical stimulation. (3) Transcranial magnetic stimulation (transcranialmagneticstimulation): a non-invasive method for preoperative functional localization of the motor cortex in parietal tumors. The navigated transcranial magnetic stimulation technique incorporates the principles of transcranial magnetic stimulation, electromyography and neuronavigation. With the help of neuronavigation, the exact cortical location that is subjected to transcranial magnetic stimulation and triggers an electromyographic response in the limb can be recorded and used to guide the safe resection of tumors in the motor area for surgery. Preoperative fiber bundle tracer imaging relies on anisotropy to measure the directionality of water diffusion along the white matter fiber bundles and produces a three-dimensional image to visualize key fiber bundles in the white matter such as the corticospinal tract, arcuate tract, and/or optic radiations, which can reflect tumor compression, nudging, or destruction of the fiber bundles and is a more reliable method to assess tumor involvement of the white matter fiber bundles. Fiber bundle tracer imaging can also help to analyze the nerve fiber connections between the brain regions we are interested in, as well as the subcortical nerve fiber pathways along the surgical pathway. Intraoperative imaging and real-time guidance of neurological functions (1) 3D fusion of multimodal medical images: the preoperative obtained CNS tumor and brain structure and function images can be fused and reconstructed to show the CNS tumor images, the intracranial arterial and venous vascular system, the location of functional brain areas, the alignment of white matter fiber bundles and the adjacent relationship with the tumor in a 3D visualization. The MRI information can also be synchronized with the metabolic images suggested by PET-CT for fusion. The 3D virtual reality environment created by the computer can help the neurosurgeon to plan the surgery preoperatively, visualize the tumor target to be resected in 3D and select the most suitable resection method. The multimodal 3D neuronavigation technology can also provide interactive dynamic information feedback during CNS tumor surgery and guide the surgeon to realize the minimally invasive concept of brain tumor surgery under 3D image guidance. However, it should be noted that since the 3D image guided images are based on preoperative imaging data, the interactive information feedback does not reflect the intraoperative real-time images. Brain drift due to the opening of the dura, loss of cerebrospinal fluid, and resection of the lesion will affect the reliability of this technique. (2) Arousal surgery with direct electrical stimulation: In arousal surgery, the patient receives cortical electrical stimulation in the awake state, and the localization of brain functions is completed according to the excitatory effect in sensory and motor areas and the inhibitory effect in language and memory, marking the brainmapping, which is the gold standard of brain function area localization technique. Arousal surgery combined with direct electrical stimulation can also identify intraoperative fiber bundle alignment and subcortical nerve fiber connections in functional areas to achieve precise localization and real-time protection of functional cortical and subcortical functional pathways in the brain during glioma resection. (3) Intraoperative magnetic resonance imaging (iMRI) overcomes the shortcomings of using preoperative imaging data for neurological navigation because it allows the patient to be scanned intraoperatively, which is prone to brain drift. It allows the surgeon to analyze the extent of tumor resection and potential neurological impact intraoperatively and determine whether further resection is needed. iMRI also allows early detection of intraoperative complications such as hemorrhage, ventricular obstruction and cerebral ischemia, and timely management. (4) Intraoperative ultrasound: In CNS tumor surgery, intraoperative ultrasound integrated with neuronavigation system can better localize and present the tumor, adjacent ventricles and tumor peripheral vasculature, display real-time images of brain tumor and guide surgical resection. Compared with iMRI, intraoperative ultrasound also has the advantages of low equipment cost, dexterity and convenience in use, short examination time and less chance of contamination. (5) Fluorescence-mediated CNS tumor surgery: Patients are orally administered 5-aminolevulinicacid (5-ALA), which is metabolized to fluorescent protoporphyrin IX through the heme synthesis pathway. With the use of a blue light surgical microscope emitting 400nm wavelength, red tumor tissue can be identified against a blue brain tissue background, which, when combined with other imaging and neurological real-time guidance techniques, facilitates the identification and removal of tumors and the protection of neurological function. Medicine is a dynamic developmental discipline, which is also fully reflected by the development of technologies related to CNS tumor surgery. Clinicians are the practitioners of CNS tumor diagnosis and treatment. We can only improve the diagnosis and treatment of CNS tumor to a new level and ultimately benefit patients if we always pay attention to the progress of CNS tumor research and translational medicine, constantly update our theoretical and technical knowledge about CNS tumor diagnosis and treatment, and carefully grasp the principles of CNS tumor diagnosis and treatment.