Functional neuronavigation Conventional neuronavigation technique is to apply anatomical images to precisely locate intracerebral lesions, to achieve small scalp incisions in cranio-cerebral surgery, to cause little nerve damage, and to meet the patient’s minimally invasive requirements. Functional neuronavigation is to use multi-image fusion technology to fuse the anatomical images showing the tumor, the images showing the functional cortex and the conduction bundles together, combined with navigation and positioning technology to achieve both total excision of the lesion and preservation of the functional brain structures (functional cortex and subcortical conduction bundles) and functions. Functional neural navigation can protect patients from postoperative limb movement, speech, and vision. 1. Functional brain imaging There are many functional areas on the surface of the brain that are in charge of movement, sensation, language and vision. These functional cortices do not differ from other cortices of the brain in appearance and can only be roughly localized by relying on the anatomical spatial location of the brain. This localization method is inaccurate, has a large error, and is susceptible to interference by various factors. There is a special imaging technique that can show the functional areas of the cerebral cortex called blood oxygen level dependent (BOLD) technique, which was first proposed by Japanese scientist Seiji Ogawa in 1990 [17].BOLD uses hemoglobin as an endogenous contrast agent and achieves imaging by changes in blood oxygen saturation levels. When neurons in functional areas of the cerebral cortex are activated, metabolism is active, followed by an increase in microcirculatory blood flow and an increase in the local oxyhemoglobin/deoxyhemoglobin ratio. Since deoxyhemoglobin is a powerful paramagnetic substance, whereas oxyhemoglobin is an anti-magnetic substance. Therefore, the signal intensity in the activated area of the cortex on T2WI is higher than that in the inactive area. The activated cortical function image can be obtained by superimposing the high signal of the activated area on the structural brain image in pseudo-color by computer image post-processing technique. At present, BOLD technique has been able to locate the important brain functional areas such as cortical motor areas (cortical first motor area, premotor area and supplementary motor area), sensory areas, language areas (sensory and motor) and visual areas more accurately. The functional areas of the brain are connected to the target organs they innervate and to the functional areas by conduction bundles. These conduction tracts are like computer networks that transmit or receive various important information and are essential for the execution of various functions of the human brain. These dense, more delicate subcortical conduction bundles are located in the white matter of the brain and are as indistinguishable from the functional cortex as the naked eye. Basser and Pierpaoli in 1996 [18,19] first reported diffusion tensor imaging (DTI), a technique that opened the door to imaging subcortical nerve bundles. Recent experimental and clinical studies have demonstrated that DTI technology can achieve 3D tracer imaging (Tractography) of subcortical neurotransmission pathways (e.g., white matter fiber bundles such as pyramidal, visual, auditory, and speech radiations) based on the anisotropic motion of water molecules within the white matter fibers of the brain, showing their morphology, structure, and direction of conduction. In addition to clinical applications, functional brain imaging is also widely used in various fields of research on higher brain functions. 2. The concept of functional neuronavigation surgery is proposed Lesions in or adjacent to functional areas of the brain (e.g., tumors, cerebral arteriovenous malformations, cavernous hemangiomas, etc.) often damage the functional cortex and/or subcortical conduction tracts during surgery, resulting in postoperative complications such as limb paralysis, aphasia, loss of reading, and visual field defects. Therefore, it has been a worldwide challenge to maximize the removal of lesions and maximize the preservation of functional structures and functions. Through experimental and clinical studies, the Department of Neurosurgery of Huashan Hospital, Shanghai Medical College, Fudan University, was the first in the world to propose and demonstrate the new concept of functional neuronavigation (FUNCTIONAL NEURONAVIGATION) surgery [20-24]. The basic principles (Figure 8) are: (1) to use conventional MRI to reconstruct the cranial structure model, BOLD to localize the functional cerebral cortex, and DTI to display the subcortical nerve conduction bundles as the basic material for multi-image fusion, respectively. (2) Apply the multimodal medical image fusion technique based on rigid body alignment to fuse the above brain structure and functional images with high precision. (3) Applying the fused images combined with neural navigation, the invisible functional brain structures become visible and are projected in the surgical field to guide the cranial surgical process. It helps to improve the lesion resection rate and avoid neurological function damage by precisely locating the adjacent neurological functional structures while clarifying the lesion boundary. 3. Clinical application of functional neuronavigation surgery Take the most common central nervous system tumor, glioma (accounting for 36% of all brain tumors and 81% of malignant brain tumors), as an example, because there is often no naked eye discernible boundary between the tumor and normal brain tissue. Therefore, despite the advances in microsurgical techniques, only about 60% of gliomas can achieve total resection in the imaging sense. Especially for gliomas in functional areas, it is particularly difficult to achieve the surgical strategy of “complete resection with maximum preservation of brain function”. The BOLD technique can accurately map the individualized distribution of higher neurological areas in the cerebral cortex, including motor, language, visual, and emotional-cognitive areas, and is therefore used for preoperative functional localization. Lehericy [25] and Wu [23] reported a controlled study of BOLD localization of the motor cortex with the “gold standard” intraoperative direct electrical stimulation technique, and the results were highly consistent. Rutten [26] and Lang [27] also showed good agreement between BOLD and electrical stimulation techniques for localizing the speech cortex. The application of BOLD images to functional neuronavigation surgery enriches the amount of information in the navigation images, enabling individualized, real-time, and precise intraoperative localization of anatomical structures and functional cortex to guide the resection of tumors, improve the rate of complete surgical resection, and reduce the rate of postoperative disability [21,28]. Similarly, the application of multi-image fusion techniques to fuse DTI nerve conduction bundle images with MRI brain structure images can clearly show the adjacent relationship between the lesion and the functional neural conduction pathways. DTI-based functional neuronavigation helps to improve the resection rate of brain tumors adjacent to the pyramidal tract, visual radiation, or speech radiation, and enables the quantitative intraoperative protection of the above important neurological conduction pathways on imaging (Figure 9), reducing the postoperative disability rate, prolonging the postoperative survival time of patients, and improving the quality of life. Since 2001, over a period of 5 years, the Department of Neurosurgery at Huashan Hospital, Shanghai Medical College of Fudan University, was the first in the world to complete a large-scale prospective randomized controlled clinical trial study (n=238) of functional navigation surgery for the treatment of glioma (brain cancer) in the motor area. The results confirmed with Class I evidence-based medical evidence that: (1) the use of the new technique can increase the surgical total resection rate of functional area glioma from 51.7% to 72.0% (close to the total resection rate of non-functional area navigation surgery). (2) The immediate postoperative disability rate was reduced from 32.8% to 15.3%. (3) The patient’s long-term neurological function score increased from 74 to 86. (4) This clinical study also confirmed the significant independent survival advantage of the new functional neuronavigation technique. That is, the new technique can reduce the risk of postoperative death by 43.0% in patients with functional malignant glioma (WHO grade 3-4) compared to conventional navigation surgery. The research results were published in the international authoritative neurosurgery journal NEUROSURGERY [24] and were highly evaluated by international colleagues, including Professor Black, President of the World Federation of Neurosurgery, Harvard Medical School, USA – “This is a landmark study that could significantly improve The results symbolize the gradual rise of Chinese neurosurgical power”. A-C, preoperative 3D reconstruction of the individualized cranial digital model of the case, with the tumor in green, the motor cortex in yellow, and the subcortical motor conduction pathway, the pyramidal bundle, in blue. d, postoperative image showing complete resection of the tumor with the motor cortex and subcortical pyramidal bundle intact.