What are the characteristics of MEG? In which fields can it be used? This article will analyze from dimensions such as technological development, application value, and industry players to unlock this cutting-edge technology that reverses brain function.
01Brain imaging technology has developed in multiple dimensions, advancing brain function research to new depths.
The study of brain activity patterns relies on various instruments for observing the brain and imaging technologies. Currently, the main brain imaging technologies can be divided into two categories: structural imaging techniques and functional imaging techniques.
Architecture is like technology:Imaging techniques that directly visualize brain structures and reflect their anatomical makeup. The main structural imaging techniques include computed tomography (CT), magnetic resonance imaging (MRI), etc.
Features are like technology:A technology that indirectly observes brain function by measuring information such as brain electrical/magnetic activity, blood flow, oxygen consumption, neurotransmitters, etc. Functional imaging techniques include electroencephalogram (EEG), magnetoencephalogram (MEG), positron emission tomography (PET), photon emission computed tomography (SPET), functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), and more.
02 Brain imaging technologies each have their own advantages and clinical applications have their own focuses
Different brain imaging techniques have their own characteristics. Structural imaging techniques such as CT and MRI are mostly used for diagnosing diseases where there are changes in brain structures, such as tumors and cerebrovascular diseases; functional imaging techniques such as EEG play an important role in the field of neurological diseases like epilepsy. PET can keenly identify non-palpable malignant tumors, while fMRI and fNIRS are mostly applied in fields such as brain function localization and cognitive psychology.
MEG, as a functional technology, identifies and locates the visual, auditory, somatosensory, and motor cortical regions of the brain by detecting magnetic field signals outside the skull. It can determine the strength and pattern of functional connections between different brain regions. MEG combines high temporal resolution (0.001s) and spatial resolution (2-5 mm), and is non-invasive and radiation-free to the human body. It is one of the most advanced technologies in the field of brain imaging at present.
Figure: Overview of the characteristics of different brain imaging techniques
Source: Public information, Frost & Sullivan analysis
Brain MRI complements other brain imaging techniques to improve the accuracy of disease diagnosis.
As an emerging brain imaging technology, MEG is mainly used in clinical applications for neurological diseases and mental disorders. With its excellent temporal and spatial resolution, MEG has irreplaceable unique advantages in these clinical scenarios. It can also be used in conjunction with other brain imaging technologies to further enhance the accuracy of diagnosis and treatment.
1) Applications of MEG in the field of neurological diseases
MEG, with its imaging characteristics, has significant application value in the fields of neurological diseases such as epilepsy, brain tumors, and stroke, especially in the localization of epileptic foci. The 'Chinese Expert Consensus on Preoperative Assessment for Epilepsy Surgery (2022 Edition)' indicates that the prevalence of epilepsy in China is about 0.7%, with a large patient population of approximately 9 million, of which about 2 to 3 million are drug-resistant epilepsy patients. Currently, treatment methods for drug-resistant epilepsy include surgical procedures, ketogenic diets, neuroregulation, etc., and 5%-10% of drug-resistant epilepsy patients can achieve epileptic remission or even termination of seizures through surgical procedures.
Intracranial electroencephalogram (iEEG) is currently an effective method for efficiently locating epileptogenic areas and assessing the relationship between epileptogenic and functional areas, but it has invasive limitations. MEG can accurately detect and locate epileptic foci without trauma, and is of great significance for localization before surgical treatment for epilepsy and determination of neuroregulatory targets. Velmurugan[1]A study published in the Brain journal indicates that the coincidence rate between MEG and high-frequency oscillators (80-200Hz) with the presumed epileptogenic regions and resected cortexes is 75.0% and 78.8%, respectively, which is superior to other frequency bands and standard dipole fitting methods. Cao[2]A paper published in Nature Communications indicates that using MEG combined with a novel dynamic network model can reconstruct clinically widely accepted virtual intracranial electrode signals. In the future, this approach is expected to reduce or even replace invasive intracranial electrode implantation for the evaluation of epileptic foci.
The 'Chinese Expert Consensus on Preoperative Assessment for Epilepsy Surgery (2022 Edition)' indicates that MEG has excellent temporal and spatial resolution. It can be used through inverse operation to determine the location, intensity, and direction of point activity sources. It can locate functions such as language, movement, sensation, vision, and hearing, and can be integrated with MRI to form magnetogenic imaging, serving as a meaningful supplement to complex epileptogenic zone localization examination techniques.
2) Applications of MEG in the field of mental illness
MEG can also be used as an adjunctive diagnostic tool for mental illnesses such as depression, schizophrenia, and autism spectrum disorder. With the help of MEG, the severity of depression can be determined by identifying signal changes in the prefrontal region and limbic grid area of patients. Nugent[3]The study involved using MEG to assess the resting state of patients with severe depression before and after ketamine use, in order to evaluate the effectiveness of treatment for depression. In addition, MEG can assist in the diagnosis of schizophrenia by identifying abnormal signals in the neural networks and regions of patients with schizophrenia; MEG can reveal brain activity during abnormal auditory, visual, and emotional events, which is used for autism diagnosis and classification.
02 Deciphering Brain Function: MRI Facilitates Brain Science Research and Development
1) Applications of MEG in cognitive science research
The time resolution of MEG is at the millisecond level, capable of tracking rapid neural activities, making it an important tool for cognitive neuroscience research such as language and perception. Team led by Professor Gao Jiahong from Peking University[4]Based on previous research on brain neural activity, combining MEG with unique language stimulation paradigms to distinguish the sites and combinations of cortical processing of words, phrases, and sentences, it was found that the superior temporal gyrus is involved in processing at three language levels. Other brain regions participate in encoding each language level through different combinations. Specifically, the neural activity of the right motor cortex only follows the rhythm of monosyllabic words with clear acoustic boundaries, while the left anterior temporal lobe and left inferior frontal gyrus selectively participate in the processing of phrases or sentences. This study successfully constructed a language structure processing atlas using MEG, providing an important tool for further research on human cognitive functions.
2) Applications of MEG in the field of brain-computer interfaces
MEG boasts excellent signal-to-noise ratio and traceability positioning capabilities. Peking University[5]Utilizing the decodable nature of brain magnetic signals to track human visual processing, it was found that different types of images exhibit a clear trend of large-scale separation in their brain representations by decoding only the brain magnetic data from half a second before seeing the image. This demonstrates the significance of MEG for constructing high-performance brain-computer interfaces. The performance of the new generation of atomic magnetometry (OPM-MEG) technology is close to that of implantable brain-computer interfaces and is expected to become the main supporting technology for future brain-computer interfaces.
The market demand for brain MRI is vast, and the new generation of brain MRI leads the trend
Currently, MEG has been preliminarily explored and applied in clinical and research fields, but its clinical application is mainly focused on epilepsy auxiliary diagnosis. MEG can be widely used in clinical areas such as cerebrovascular diseases, post-traumatic brain function assessment, mental illnesses, and psychological disorders, and also holds significant value for cognitive science. After the emergence of OPM technology, the detection performance of MEG has improved, installation and use have become more flexible, and costs have been significantly reduced. It will be promoted and used in more medical and research institutions, providing diagnostic support for patients with various types of neurological and psychiatric system diseases, technical support for cutting-edge fields such as deeper cognitive studies and brain-computer interfaces, and has broad application prospects.
01 The evolution of brain magnetic technology continues, and OPM technology is highly sought-after
The propagation of brain neural currents generates magnetic fields, and the magnetic permeability of different brain tissues is almost identical, making brain magnetic fields an ideal signal for detecting brain function. However, the intensity of brain magnetic fields outside the skull is only on the order of 10^-100 fT, about one billionth of the Earth's magnetic field, making it difficult to detect. In 1968, American physicist Cohen used multi-turn induction coils to detect human brain alpha wave signals for the first time in a specially constructed magnetic shielded room. In 1972, Josephson junction superconducting quantum interference devices (SQUIDs) technology was born and could efficiently detect brain magnetic signals, marking the commercialization of magnetoencephalography (MEG). In 2002, the Romalis team at Princeton University first achieved atomic spin-free exchange relaxation (SERF) states and built an atomic magnetometer (OPM) system capable of measuring fT-level sensitivity in 2003, making room temperature brain magnetic detection a reality.
Figure: Key events in the development of brain magnetic technology
Source: Literature search[6 - 10]Frost & Sullivan analysis
02 The superconducting quantum interference device (SQUID) has been successfully commercialized, but its popularization is limited.
The Superconducting Quantum Interferometer SQUID, based on the superconducting Josephson effect and flux quantization technology, is a highly sensitive flux detector capable of converting magnetic flux into voltage. Under ideal laboratory conditions, the sensitivity of SQUID-MEG can reach 1 fT/√Hz, while commercial SQUID-MEGs typically have a sensitivity of 2-3 fT/√Hz. Currently, SQUID-MEG has been applied in clinical and research fields, mostly used by medical institutions for epilepsy diagnosis. However, domestically, SQUID-MEGs rely on imports, with about 20 units in use, mainly located in domestic universities, research institutions, or top-tier hospitals, resulting in a low penetration rate. This is due to issues such as the high cost (about 30 million per unit), large size, need for liquid helium to maintain superconducting state, high operating costs, expensive shielding rooms and large floor space requirements, and poor flexibility of SQUID-MEG products.
Figure: SQUID-MEG Promotion Challenge
Source: Literature search[6]Frost & Sullivan analysis
The new generation of brain MRI has significant advantages and will accelerate the popularization of MEG.
OPM-MEG is a technology that uses the interaction between light and atoms to detect magnetic fields. Based on SERF theory, when a beam of circularly polarized pump light irradiates alkali metal atoms, the atoms undergo energy level transitions, generating spin polarization; under the influence of an external weak magnetic field, the alkali metal atoms undergo Raman pumping and produce an inelasticity polarization angle, whose magnitude is proportional to the magnetic field strength within a certain range; when another beam of polarizing detection light is perpendicular to the pump light, the polarization direction of the alkali metal atoms undergoes a slight deflection, and by detecting changes in the polarization angle, the magnitude of the magnetic field can be directly reflected. Theoretical calculations show that the sensitivity of an atomic magnetometer without spin exchange relaxation can reach 0.01fT/√Hz or even lower; in laboratories, a sensitivity of 0.16fT/√Hz has been achieved, which is currently the most sensitive magnetic detection physical technology mastered by humanity.
Figure: Comparison between SQUID and OPM technologies
Source: Literature search[6]Frost & Sullivan analysis
Supported by the SERF theory, OPM-MEG technology has developed rapidly. In 2010, Johnson et al. used SERF magnetometers based on Rb alkali metal atoms to detect brain magnetic fields and compared them with commercial SQUID-based brain magnetic systems, proving the effectiveness of OPM-MEG. In 2017, the Sir Peter Mansfield Imaging Centre at the University of Nottingham in the UK successfully recorded brain magnetic signals and spatial localization using room-temperature atomic magnetometers for the first time. As research on OPM-MEG continues to deepen, scientists have developed smaller detectors through methods such as reducing the volume of atomic vapor chambers, adopting microelectromechanical technology, and integrating component devices. Currently, the cross-sectional area of OPM-MEG detectors has been reduced to the size of a coin. The reduction in detector volume has further promoted the development of multi-channel integrated OPM-MEGs, with over a hundred-channel products already developed. However, there are currently no commercially available clinical brain magnetic imaging systems based on OPM technology globally. In China, there are already approved clinical products for cardiac magnetic mapping due to the heart magnetic field strength being in the range of 1,000-10,000 fT, making it less difficult to detect than brain magnetic fields.
Figure: OPM-MEG Advantage Analysis
Source: Public information, Frost & Sullivan analysis
The research on OPM-MEG continues to heat up, with foreign institutions such as Princeton University and the University of Nottingham, as well as domestic universities and research institutions like Peking University, the Chinese Academy of Sciences, and Beihang University, actively engaging in this field. OPM-MEG not only features highly technical detectors, but also related technologies such as magnetic shielding devices and magnetic inversion pose challenges that must be overcome in the development of OPM-MEG products. Additionally, since product research is different from laboratory research, industrialization bottlenecks are high, and research teams that combine detector, magnetic shielding device, and magnetic inversion technologies have an advantage in the commercialization process of products.
01 The country has included brain magnetic technology in key development areas and encouraged the establishment of imaging centers
As an important tool for brain function research, MEG has received high attention from the state. Led by the Ministry of Industry and Information Technology, the '14th Five-Year Plan' for the development of medical equipment industry jointly issued by ten national departments includes brain magnetic measurement as a key development area and high-precision magnetic field sensors as the core component of industrial basic research efforts; the '14th Five-Year Plan' for the development of the pharmaceutical industry proposes to vigorously promote innovative product research and development, focusing on developing new medical imaging, wearable monitoring, and other medical devices in the field of medical devices; the General Office of the State Council has issued the '14th Five-Year Plan' for National Health to guide and promote the standardized development of independent medical imaging center institutions. In an environment favorable to policies, brain magnetic technology will achieve rapid development, with accelerated research and development and market access for clinical brain MRI, and expanded application scenarios driven by the standardized development of medical imaging centers, increasing market penetration rates.
02 Brain MRI upgrades, with better performance in the future
Public information shows that there are approximately 150 to 200 MEG devices globally. China has successively introduced multiple MEG devices after 2000, but domestic MEGs have been used for too long and are outdated. For example, the MEG at Guangdong Sanjiu Brain Hospital has been in use for over 20 years, and the MEG equipment at Nanjing Brain Hospital has been in use for nearly 20 years. It is generally recommended that large medical equipment be replaced after 10 years of service. Currently, the main type of MEG in use in China is the SQUID-MEG, but in recent years, China has already launched self-developed OPM-MEG research machines on the market. In the future, as OPM-MEG technology further matures, MEG will develop towards miniaturization, individualization, wearable devices, and flexible venues, with installation and maintenance costs continuously decreasing; OPM-MEG will achieve higher sensitivity and provide higher-quality data. The new generation of brain MRI, with its advantages, will open up a new era of brain magnetic measurement.
01 SQUID-MEG Competitive Landscape
The SQUID-MEG technology is mature, with 306-channel products already available, capable of achieving full brain coverage. Foreign companies that have deployed SQUID-MEG mainly include MEGIN, Compumedics, CTF MEG, etc., each with its own unique features.
Figure: Analysis of Major SQUID-MEG Products
Data source: Company official website, Frost & Sullivan analysis
MEGIN:MEGIN has rich experience in the field of magnetic resonance imaging (MRI) technology. The company targets the epilepsy market, with its product TRIUX™ neo which can non-invasively locate epileptic activity areas within the brain. When used in conjunction with other brain imaging techniques, it can be used in neurosurgery. The company's product Elekta Neuromag TRIUX is the only MRI product in China with a NMPA registration certificate (registration number: Guoyan Zhujin 20162210041). MEGIN was acquired by Elekta and then split and sold to Croton Healthcare in 2018.
TRIUX™ neo
Compumedics:Compumedics was established in 1985 and is a global leader in electromagnetic source localization, multimodal neuroimaging, high-density EEG, and fMRI technologies. The core patented technology of the company's SQUID-MEG product Orion LifeSpan™ MEG is the dual-relaxation oscillating superconducting quantum interference detector (DROS SQUID), which has a signal-to-noise ratio superior to traditional SQUID detectors and has been approved by the FDA and KFDA for clinical use.
Orion LifeSpan™ MEG
CTF MEG:CTF MEG was established in 1970. In 2009, CTF MEG acquired 4D Neuroimaging. In 2014, it developed the 275-channel SQUID-MEG product cMEG, which was launched as a clinically friendly version in 2019. cMEG operates stably, with high detector density, electronic components featuring high bandwidth, high conversion rate, high sampling rate, and fast data storage speed.
CMEG
02 OPM-MEG Competitive Landscape
According to public information, several domestic and international companies have deployed in the OPM-MEG field, including Cerca, FieldLine, Kunmai Medical, Magnetic Wave Intelligence, and Zhongke Zhiying. At the same time, American company QuSpin, as an OPM detector R&D enterprise, has a new generation of OPM technology detector product QZFM Gen-3 with superior performance. It has a sensitivity of 7-10 fT/√Hz and is about 2 cm² in size, and is used by OPM-MEG R&D companies such as Cerca and Magnetic Wave Intelligence. As a cutting-edge magnetic field detection technology, OPM can be used in sensitive fields such as military and aviation. Over-reliance on detectors developed abroad poses a risk of sanctions. Currently, Chinese enterprises have already adopted self-developed OPM detectors for MEG R&D. The full equipment self-development model is self-controllable and can effectively avoid risks.
Cerca:Cerca, incubated by the University of Nottingham and a spin-off of the Nobel Prize-winning laboratory Peter Mansfield Imaging Centre, uses QuSpin's detectors to develop the world's first commercial, fully integrated, head-mounted MEG research machine based on OPM technology. The device can measure the magnetic field at 50 locations around the scalp, achieving full coverage of the brain and detecting changes as subjects move. It is suitable for adults and children but still requires use in a 1.3m*1.3m magnetic shielded room.
Cerca OPM-MEG
FieldLine:The FieldLine's marketed product, the HEDscan™ system, is a non-invasive, wearable MEG device based on OPM detector technology. The device utilizes a self-developed small quantum detector placed on the head (sensitivity 15fT/√Hz, cross-section about 2cm²), capable of recording and mapping neural activity with high fidelity; it can be used in any room of any medical institution with only the aid of a magnetic shielding cylinder; the helmet is lightweight and highly wearable, suitable for people of all ages and head sizes.
HEDscan™
Kunmai Medical:Kunmai Medical is a medical technology company centered on quantum manipulation and detection technology, dedicated to developing biofunctional magnetic imaging devices. The company has participated in the construction of several major national scientific and technological infrastructure projects and has completed the first domestic scientific research installation, earning the title of 'Domestic High-End Equipment Scientific Research Demonstration Application'. The core product OPM-MEG, independently developed, has broken through a series of technologies including high-sensitivity magnetic sensing (12-15fT/√Hz), open magnetic shielding, and high-precision magnetic inversion, with a detector cross-sectional area of about 3cm². Kunmai Medical is the first and currently only company in China to have passed the innovative medical device review for OPM-MEG. The clinical machine is under medical device registration approval and is expected to become the world's first commercially available clinical OPM-MEG.
Kunmai Medical OPM-MEG*
*: The figure on the right shows the Beijing Huairou Multimodal Cross-Scale Biomedical Imaging Facility co-built by Kunmai Medical.
Magnetic Wave Intelligence:Magnetic Wave Intelligence is a technology company dedicated to the research and development of magnetic wave diagnosis and treatment technology. Its team members have rich experience in quantum sensing, human weak signal detection, and other fields. The company uses its self-developed ultra-sensitive magnetic sensor MagneticWave or QuSpin detector products, paired with high-performance magnetic shielding cylinders, to provide customized scientific research services. At the same time, the company also distributes magnetic sensors from QuSpin, FieldLine, and Twinleaf.
Magnetic wave intelligent self-developed magnetic shielding equipment
Zhongke Zhiying:Zhongke Zhiyin was established in 2019 and incubated by the Institute of Biophysics, Chinese Academy of Sciences. Zhongke Zhiyin is committed to the research, development, production, and service of new types of bio-magnetic detection equipment such as magnetic resonance imaging (MRI). The company has obtained multiple domestic and international invention patents in the field of MRI and zero-field weak magnetic detection technology, and has set up a North American technology R&D center.
Zhongke Zhiying OPM-MEG
03 Domestic MRI Procurement
In the past, China's magnetic resonance imaging (MRI) highly relied on imports. According to data from the China Government Procurement Network and China International Bidding Network, since 2014, Chinese universities, research institutions, and medical institutions have purchased a total of 18 MRI machines, including 12 SQUID-MEG machines and 6 OPM-MEG machines. Among them, 3 are from Kunmai Medical, while the procurement price of OPM-MEG is much lower than that of SQUID-MEG. It is not difficult to find that currently, the Chinese brain MRI market is mainly dominated by SQUID-MEG, while the commercialization process of OPM-MEG in China is accelerating. According to current public information, Kunmai Medical and Magnetic Wave Intelligence have already launched research machine products, and Kunmai Medical's clinical machines are under registration. It is expected that OPM-MEG products will be approved for market launch soon.
Figure: Analysis of Domestic MEG Procurement (2014-2023)
Source: Government official website, Frost & Sullivan analysis
In the future, with the further commercialization of OPM-MEG research machines and their launch on the market for clinical use, OPM-MEG will be used by more medical institutions and brain research organizations. It will bring better diagnostic options and more affordable prices to patients with neurological and mental diseases, accelerating humanity's understanding of the brain. OPM-MEG will occupy an important position in the brain imaging market with its technological and application advantages.
