"Precise and non-invasive" access to brain surgery is no longer a scene in science fiction movies.
With the development of neuroimaging, preoperative target localization has become more precise. In the process of magnetic wave knife**, the time and process of using magnetic resonance to locate the ** target is equivalent to a CT examination that can be completed in as little as half an hour for the patient. Wang Meiyun, director of the imaging department of Henan Provincial People's Hospital, described it to the first financial reporter.
The neural circuits of the brain of depressed patients have iconic biomarkers, and magnetic wave knife surgery is more like a doctor doing a "brain massage" on the nerves. Sun Bomin, director of the Center for Functional Neurosurgery at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine and former president of the Asian Society of Functional Neurosurgery, is inclined to use this metaphor to describe the patient experience of magnetic wave knife ** - *, in which the patient is always awake, and the doctor can observe the effect of ultrasound when "regulating" the different positions of the patient's nerve nuclei through magnetic resonance, and adjust the stimulation intensity according to the patient's feedback.
At the recently held "2023 'Magnetic Knife' Asian Neuroscience Innovation Scholars Summit", the latest clinical data provided by Sun Bomin to the first financial reporter showed that in the Encephalopathy Center of Shanghai International Medical Center, more than 40 patients with depression and other mental illnesses have been completed so far, of which 20 30 patients have reached complete postoperative surgery, and other patients have also improved to varying degrees.
The brain "magnetic wave knife"**, also known as "magnetic resonance-guided focused ultrasound (MRGFUS)", integrates focused ultrasound and magnetic resonance imaging, and uses the thermal effect of magnetic resonance image guidance and ultrasound focused energy to achieve biological destruction of the target and achieve a non-invasive brain-computer connection for central nervous system diseases.
In 2021, the China Medical Products Administration (NMPA) approved it for the treatment of "Magnetic Knife"** drug-refractory essential tremor and Parkinson's disease with tremor-dominated disease. At present, the application of "magnetic wave knife" in mental diseases such as refractory depression, obsessive-compulsive disorder and anorexia nervosa has also entered the clinical research stage in China.
Magnetic Wave Knife has great potential for mental illness**.
The so-called "magnetic resonance-guided focused ultrasound" is to achieve the purpose of "positioning" and "thermal adjustment". The patient only needs to lie down, and the doctor moves the mouse to find the positioning target on the nerve nucleus of the patient's brain, and the ultrasound stimulation with certain parameters is input to the target by an external device, which can be completed.
At present, the long-term dependence of mentally ill patients on medications** not only poses a heavy burden of disease and drug resistance to patients, but also means that patients will always be wobbling on a seesaw, and their symptoms will often recur.
However, as neuromodulation surgery enters the era of "precision and non-invasive", patients with a variety of refractory mental illnesses are expected to find specific neurological biomarkers and stimulation targets, and obtain the possibility of significant improvement in their symptoms and even the disease.
In Sun Bomin's view, mental illness is the most potential application field of magnetic wave knife. On the one hand, it is because of the unmet clinical needs of mental illness in ChinaOn the other hand, compared with drug control, non-invasive surgery has irreplaceable advantages in refractory depression, anorexia nervosa, sleep disorders and other diseases**.
Taking depression as an example, a research article published in China Chronic Disease Prevention and Control in September this year showed that depression is one of the most common global, disabling diseases, with an estimated global prevalence of 26.4 billion. The lifetime prevalence of depressive disorders in China is 68%, with a prevalence of 36%, of which the lifetime prevalence and 12-month prevalence of depression reached 34% and 21%。
At the same time, not all patients are able to accept the norms, and even if they do, not all of them can have good results. Approximately 50% of patients with depression receiving first-line antidepressants** do not achieve remission, and approximately 2 to 3 patients require further sequential** to achieve symptom relief.
In April this year, a study results on refractory depression in the field of brain science released by Shanghai Ruijin Hospital showed that the use of brain-computer connection to regulate nerves improved the depressive symptoms of patients with major depression by more than 60% on average.
Sun Bomin previously mentioned in an interview with ** that when the patient's symptoms begin to improve, the energy in the slow-wave frequency band of the depression circuit of the nervous system will rise, "This may be a sign of the change of depression symptoms, which is also called 'biomarker'." ”
He further told reporters that depression, anxiety and obsessive-compulsive disorder can actually be regarded as a syndrome of diseases, with multiple ** targets in the brain's neural circuits, and brain pacemakers ** (deep brain stimulation, DBS) in the past few years have shown good ** results.
After the discovery of biomarkers, there is another risk point that the industry is always concerned about when the invasive non-invasive device is used to stimulate neurons: will the disease be ** when the external stimulation is stopped?Does repeated stimulation damage nerves?
In 2021, Sun Bomin's team completed the world's first neuromodulation surgery that uses a brain pacemaker with brain-computer interface function to stimulate ** depression through multi-target combination. During the two-year postoperative follow-up, Sun Bomin found that although the patient had some hypomanic symptoms, it had significantly improved compared with the previous major depressive disorder with frequent suicidal tendencies.
But he also mentioned that the brain pacemaker is reversible and adjustable, with little trauma, but it cannot achieve the best effect, and when the external stimulation stops, the improvement of the disease may weaken over time, and long-term postoperative management is requiredAt the same time, as an invasive procedure, if the parameters of an electrode stimulation are deviated, the results are often irreversible.
Because a craniotomy is still required, DBS is similar to earlier disfigurements and inevitably carries a risk of intracranial hemorrhage. The data show that in DBS**, the rate of intracranial hemorrhage is approximately 1 200. This also means that when a hospital performs four or five hundred pacemaker surgeries a year, there is always one or two hemorrhagic patients.
Younger and mentally sensitive patients (compared to depressed patients) are more resistant to trauma**, and patients with poor coagulation are less tolerant of DBS**. Sun Bomin added.
Sun Bomin said that focused ultrasound (magnetic wave knife) can be regarded as a kind of "quasi-damage**", if it is really cured, there is no need for repeated surgery, continuous stimulation. At present, among the patients enrolled in our clinical program, for patients who do not improve significantly, they can continue to perform neuromodulation by focused ultrasound after a period of interval, which will not cause damage to the human body. Sun Bomin said.
In addition to focused ultrasound, there is another physical means that utilizes non-invasive brain-computer grafting for psychiatric disorders, namely transcranial magnetic stimulation (TMS).
Li Yongjie, director of the Neurological Center of the University of Hong Kong-Shenzhen Hospital and former director of the Beijing Institute of Functional Neurosurgery, told reporters that the effect of TMS** is not sustainable. As the electromagnetic field stimulus wears off, the patient may re** within a week or two after the end of the procedure, suggesting that TMS needs to be repeated**;In addition, transcranial magnetism has a better effect on the cerebral cortex and less effective on the deep part of the brain, while focused ultrasound can "penetrate" the skull and "reach" deep into the brain nerve nucleus, focusing on a specific target for lesion ablation. The industry expects more from the latter.
How long has the magnetic wave knife been commercially available?
Although the clinical effect is beginning to show, as a cutting-edge technology, there are still many difficulties to overcome in terms of mental illness** from clinical trials to large-scale commercialization.
The first hurdle is how to judge and select the right surgical patient. Sun Bomin said that patients with refractory mental illness who are ineffective with drugs and have a high risk of death have the need for surgery**. However, it is not neurosurgeons but psychiatrists who are qualified to diagnose mental illness, and psychiatrists still have concerns about surgical ** mental illness.
In my opinion, neurosurgery is still in the early stages of exploration. The president of a psychiatric hospital in the north told reporters. He also mentioned that although the demand for medical treatment for mental illness in China has increased significantly in recent years, the number of psychiatrists has not increased significantly. In addition, the qualification level of psychiatrists is at a lower level than that of other departments, whether it is a specialist or a general hospital. For example, different doctors may make different judgments about whether the same patient has major depressive disorder.
The patient's skull density also affects the feasibility and effectiveness of the patient. Sun Bomin mentioned a type of case, when the skull of a patient with refractory mental illness is thin, after the ultrasound penetrates his skull, scattering may occur, because the ultrasound of "running around" cannot be heated to more than 50, and finally can only take other best measures for such patients.
In addition, as a high-value product, the higher installed capacity and ** cost also affect patient accessibility.
The Magnetic Knife originated from Insightec, an innovative Israeli medical technology company, and this technology was named one of the 50 best inventions of the year by Time magazine in 2011. In 2021, the indication of "Magnetic Wave Knife" for "clinical, drug-refractory essential tremor and Parkinson's disease dominated by tremor" was approved for marketing in China. In the same year, the "magnetic wave knife" independently developed by local companies also entered the clinical stage, but the indications of related device products focused on the field of tumors. In the past 3 years since it was listed, the number of installed units in China is not much. According to the latest data from Medical TV, a total of 6 units are currently installed in Beijing, Guangdong Province, Henan Province and Shanghai. According to a previous report by Yicai, the cost of ** is more than 100,000 yuan.
Qiu Peng, general manager of MediTV China, told reporters that a high-value innovative medical device is indispensable for large-scale commercial use in China. From this point of view, the promotion of the "magnetic wave knife" method in China still needs to be more localized and imported magnetic wave knife equipment registered and listed in China, as well as the expansion of the indications of "magnetic wave knife" in the field of psychiatric, tumor and other diseases.