Apparatus and methods for cooling the brain through the cistema magna and diagnosing and treating glioblastoma

Abstract

A method and apparatus for preventing brain death by using rapid and safe cooling of the brain is disclosed. The fourth ventricle is accessed through the patient's neck by using a specially designed needle / cannula that enters the cistema magna with an entry through the patient's neck, allowing the cooled artificial cerebral spinal fluid (aCSF) to flow around the brain. The aCSF exits from an opening in the skull where temperature / pressure sensors are placed. Data is sent to a computer controlled motorized system that pumps the cooled aCSF to the needle / cannula placed in the cistema magna. The pumping of the aCSF is controlled to maintain a predetermined temperature and / or pressure of the outlet aCSF.

Description

[0001] This application claims priority under 35 USC 119 to U.S. Provisional Patent Application Serial No. 62 / 905,996, filed September 25, 2019, which is incorporated herein by reference. TECHNICAL FIELD

[0002] The illustrated embodiments are directed to a unique approach to safely and rapidly cool the brain to deep hypothermia (20 to 25 degrees Celsius using artificial cerebrospinal fluid (aCSF) cooled to 1-10°C) for the prevention of brain death in the absence of blood circulation to the brain, including diseases such as cardiac arrest due to myocardial infarction, stroke, and exsanguination. BACKGROUND

[0003] Fifty years ago, Professor Robert White proved that cooling a monkey’s brain to 15 degrees Celsius, with all major blood vessels bound at the neck, would protect the structure and function of the brain in the absence of blood circulation to the brain for one hour. When the tourniquet around all the neck blood vessels was released after one hour, the monkey was given time to return to room temperature, after which tests showed no deterioration in memory, problem solving, and motor activity.

[0004] Now, the results of Professor White’s new work are currently being successfully used by cardiothoracic surgeons who repair the aortic arch with aortic prostheses, such as in the case of Marfan syndrome with aortic dissection as depicted in FIG. 4. With almost no blood to the brain, they can get 30 minutes of operating time if they pre-cool the brain to 10 degrees Celsius. By directing extremely cold saline into the subclavian artery, they can achieve this temperature in the brain. This is quite successful, with the result being the prevention of brain damage without loss of memory or function. FIG. 4 highlights the importance of the extensive medical literature outside of neurology and neurosurgery. In 1975, Griepp et al. first reported in the cardiothoracic literature of lowering brain temperature to deep hypothermia with cardiopulmonary bypass. They successfully preserved brain function with replacement of the aortic arch, despite cardiac arrest in their patients. For such surgeries, common medical practice is to include deep hypothermia to place the brain in “suspended animation” for 30 minutes or more without blood to the brain.

[0005] By lowering the temperature of the brain to extreme hypothermia, the brain can be placed in a suspended animation state, despite the absence of blood flow. In The Lancet (355 (9201) 375-376) reported a 29-year-old radiologist, Anna Bågenholm, who had been accidentally submerged and frozen to 13.7 degrees Celsius with a flat electrocardiogram. After being revived and returned to normal temperature, she fully recovered all mental capabilities. In November 2019, Samuel Tisherman, MD, was reported to treat severely injured patients by using chilled saline to enter the brain blood vessels circulation, and by cooling the brain to extreme hypothermia. Two hours after the low temperature, he was able to complete the surgical repair, and then revive the patient.

[0006] It has been reported that children who fell into a freezing lake survived without apparent brain damage after being submerged in extreme hypothermia for 1 hour or more - in similarly challenging situations, adults would not survive in freezing water, as children can have open fontanelles and thinner skulls allowing rapid cooling of the brain. Today, infants and children at risk of ischemic brain injury are treated with moderate to mild hypothermia, with increased survival and less brain damage compared to children who do not lower their body temperature.

[0007] Many reports have investigated the use of mild to moderate hypothermia in the case of a heart attack, lowering the body temperature to only 33 degrees Celsius, with different success reports in the analysis of the results. Lowering the body temperature to less than 33 degrees Celsius can cause arrhythmia (due to harmful effects on the ventricles) and bleeding problems (due to the interruption of platelet aggregation leading to bleeding).

[0008] In the presence of a blood interruption to the brain, we can have only a few minutes before there is irreversible brain damage. While cardiopulmonary resuscitation (CPR) has been the standard treatment for cardiac arrest, even successful cases can result in a stroke with significant brain tissue disability. In addition to cardiac arrest, major strokes and blood loss are major life-threatening problems that need to be treated within the first few minutes of brain blood circulation deficiency. Ways to extend brain survival for an hour or more in the case of circulatory arrest are needed. This search for ways to extend the "golden hour" will give the treating physician the opportunity to deal with the urgent problem and its cause. If the brain can be placed in suspended animation for an hour or more, it will cause a shift in the pattern of patient medical care. If the brain can be protected from ischemic damage by quickly and effectively using deep hypothermia, the restoration of circulation and repair of injured organs and tissues will be possible. Giving an hour instead of just five minutes, the treating physician will have the opportunity to save the patient. SUMMARY

[0009] In the deep hypothermia ( < 14 degrees Celsius) range, such hypothermia can be achieved using techniques that cool the brain with artificial cerebrospinal fluid (aCSF). While undergoing clinical improvements, for the purposes of this patent, the target temperature range using "deep" hypothermia is consistent with the surgical technique of "deep hypothermic circulatory arrest" (DHCA). A review of the historical transition of this mode at near deep hypothermia of the brain, current work, and rationale is presented.

[0010] Illustrative embodiments of the present invention provide apparatus and methods for preventing brain death due to interruption of blood circulation to the brain due to cardiac arrest, stroke, loss of blood due to blood letting, and other causes. By selectively cooling the brain, the brain can be placed in "suspended animation" for an hour or more without circulating blood flow. Instead of only 5 minutes to save a patient from impending brain death, the treating physician will have an hour or more to save the patient's life. By directly cooling the cerebrospinal fluid, it is possible to cool the brain without using direct access to the cerebral vascular circulation by intubating the aorta or large vessels that lead to the brain. The time required for circulatory intubation makes it difficult to perform quickly, and the problems of systemic cooling can lead to arrhythmias and hemorrhage.

[0011] Accordingly, the mode shift of rapidly cooling the brain requires new ways. The apparatus of the illustrative embodiments is required to safely, accurately, and atraumatically quickly access the cistema magna. Because the first person available to insert a needle into the brain can be a caregiver, the procedure must be well-documented, easy to use, and quickly administered. Once in place, the needle must be secured to a stable anatomical site, and the sharp cutting tip of the needle must be changed in shape to prevent damage to brain tissue in the cistema magna and brain stem. In a battlefield situation, when used by a caregiver, the design of a similar needle system for accessing large vessels such as the femoral artery must be accomplished safely and quickly.

[0012] Method for cooling the brain through the cistema magna

[0013] Safety, accuracy, and speed are the hallmarks of the illustrated embodiments to quickly prevent brain death in emergency situations that have a patient with an acute interruption of blood circulation to the brain that will result in brain death. Clinically, during surgery, the brain can be placed in suspended animation to pump chilled saline into the brain through a bypass to the subclavian artery to replace a dissecting aortic aneurysm. This is done quite successfully in humans around the world.

[0014] Our laboratory research has proven that the brain in experimental animals can be rapidly cooled to deep hypothermia, or even lowered to extreme hypothermia. By circulating cooled artificial cooling substance (aCSF) around the brain to rapidly cool the cerebrospinal fluid (CSF), the central nervous system (CNS) will also be cooled by the vasoconstriction in the floor of the cistern and the brain within the subarachnoid space. We have found that access to the subarachnoid space can be rapidly and safely achieved by accessing the cisterna magna through a lateral approach from behind the head and neck junction or from under the mastoid process. Because the needle access is close to the brain stem and vertebral arteries, this must be done with direct visualization using ultrasound direction through the needle and around the needle. The drain must be placed in the forehead (near the hairline) to evacuate the aCSF from the head and allow convective cooling. This drain is a new design for a trephine that is rapidly inserted, stable, free from injury to the brain, accurately placed, and performed by a single person semi-autonomously. The outlet fluid is warmer near the frontal lobe than the colder fluid near the occiput when the patient is supine. The subarachnoid space is relatively larger in older patients, and a larger volume of aCSF provides greater cooling effect.

[0015] A different configuration allows the aCSF to exit the trephine and be recirculated into the cisterna magna. The drain opening is connected to a sterile drain system or to a pump system to recirculate the aCSF, which is information controlled via tubing from the forehead for temperature and pressure measurements. The temperature of the outlet aCSF is monitored as well as the temperature entering at the cisterna magna. The cooling system integrates a refrigeration unit and a peristaltic pump. If a closed system is used, a filter system is in line with the closed system to remove debris and contaminants and infectious agents from the path of fluid exiting the front of the brain; thus, convective cooling will occur, causing the brain to cool rapidly better. The virtual "pump" created by the convective cooling will act as an additional "motor" within the skull to facilitate rapid cooling.

[0016] In effect, the recirculated cooled aCSF is in a closed and sterile system that will cool the structures of the brain within the cisterna magna and subarachnoid space. The initial cooling is provided to the blood vessels at the base of the brain, thus circulating cooled blood through the brain tissue. The cooled aCSF will cool the base of the brain and important structures including memory directly. From there the cooled aCSF will pass around the brain within the subarachnoid space. In the supine position, there is a temperature difference between the cooled fluid near the occiput and the warm fluid at the front of the brain where the outlet fluid is, thus, convective cooling will occur to cause the brain to cool rapidly better. The virtual pump created by the convective cooling will act as an additional pump within the skull to facilitate rapid cooling.

[0017] While the devices and methods have been or will be described in the context of functional explanations with respect to grammatical flow, it should be appreciated that the claims should not be construed as necessarily limited by the construction of "means" or "steps" for performing the described functions, unless such construction of claim limitations is explicitly recited by the claims according to 35 USC 112, but rather should be given the full scope of equivalents, implicit recitations and permutations of claim limitations as provided under the judicial doctrine of equivalents to the definition provided in the claims as per 35 USC 112, and to the full extent indicated, if a claim is expressly drafted under 35 USC 112. The disclosure can be better visualized by now referring to the following drawings in which like elements are referred to by like reference numerals. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 Simplified side cutaway schematic of a human head showing the elements of a cooling system with a pump and chiller that administers artificial cerebrospinal fluid (aCSF) through a fixed needle in the cistema magna, the cooled aCSF circulates through the subarachnoid space around the skull, and drains into a sterile container.

[0019] Figure 2 Simplified side cutaway schematic of a human head showing the recirculation of aCSF from an exit port in the skull to the pump, filter, and cooling system, and then back into the subarachnoid space through a fixed needle in the cistema magna.

[0020] Figure 3 Simplified side cutaway schematic of a human head showing a specially designed unit, a semi-automated trephine, placed in the skull and in the subarachnoid space for the egress of aCSF after it has circulated through the subarachnoid space. It also includes a temperature sensor and pressure monitor.

[0021] Figure 4 is a schematic of a prosthesis used in the surgical repair of a dissecting aortic aneurysm in Marfan's Syndrome using current technology that requires the use of deep hypothermia to prevent brain death, proving that "life pause" by cooling the brain has been successfully used worldwide since 1975.

[0022] Figure 5 Simplified side cutaway schematic of a human head showing a new technology for accessing the cistema magna from a lateral approach, first reported in 2018 using a different approach, that has the advantage of being adjacent to the mastoid bone for positioning and fixation of the needle to the bony anatomy.

[0023] Figure 6This diagram illustrates a simplified lateral cross-section of a human body used for cooling the spinal cord via a lumbar puncture, inserting a needle through the subarachnoid space of the cerebellomedullary cistern and spinal canal. A pump / cooling system guides the cooled aCSF down the spinal canal by circulating it into the cerebellomedullary cistern and guiding it out of the lumbar puncture. Depending on the situation, the cooled aCSF may be guided into the lumbar puncture needle and exit through the cerebellomedullary cistern.

[0024] Figure 7 A simplified lateral sectional view of the human body is shown, illustrating a method of cooling both the brain and spinal cord by using cooled aCSF at the entry point of the cerebellomedullary cistern and at the exit port of the skull and below the lumbar puncture.

[0025] Figure 8 A simplified side cross-sectional diagram of the human head is shown, illustrating the advantages of using convection cooling to cool the brain more rapidly when the patient is supine, with the colder CSF below and the warmer CSF above, producing an additional "motion" effect that causes the brain to cool even faster.

[0026] Figure 9 This is a schematic diagram of the components of a phased array ultrasound device inside a 2mm diameter cannula (within a 17-gauge needle), which includes the needle, an electronic interface unit, and a portable handheld monitor.

[0027] Figure 10 for Figure 9 A schematic diagram of the transmission and reception ends of an ultrasound device, showing the use of 64 or more elements in phased array imaging, a field of view of up to 30 degrees or more, and a penetration of up to 2.5 cm.

[0028] Figure 11 This image illustrates a stereoscopic view of the tip of an ultrasonic needle using a concept based on a temperature-sensitive alloy such as nitinol at different times. After the needle penetrates into the cerebellomedullary cistern, the cooled aCSF entering the needle causes a shape change, blunting the cutting edge, particularly the tip. Furthermore, the temperature-sensitive alloy allows the tip to be reshaped to allow aCSF flow with less turbulence and more direct flow over the nerve tissue.

[0029] Figure 12 This is a simplified side sectional view of the human head, showing a "cranial cap" that will be fitted like an exoskeleton to provide fixation and stability for the ultrasonic needle unit.

[0030] Figure 13 A simplified side sectional view of the human head shows a band extending from the forehead to the upper cervical spine, providing support and fixation for the needle using semi-rigid units. It is strong enough to allow attachment to... Figure 14The servo motor system described in the middle. The anterior fixation provided by the screw in the burr is fixed in the frontal bone. The posterior fixation point acts as a firm fitting exoskeleton like a "skull cap" or similar device over the head and upper neck to give stability and precision to the ultrasound needle into the neck and into the cistema magna.

[0031] Figure 14 To enable semi-autonomous or robotic insertion of the phased array ultrasound needle into the cistema magna or femoral artery Figure 15 Schematic of the system in the cistema magna or femoral artery described in the middle. Once the needle is in place, the information from the phased array ultrasound needle is sent to the microprocessor / artificial intelligence unit and then to the servo motor that controls the needle insertion to the target site. This requires a firm and stable fixation unit, like Figure 13 shown.

[0032] Figure 15 Simplified anterior cross-sectional schematic of the femoral artery target site for needle entry and associated anatomy.

[0033] Figure 16 Schematic of the aorta showing the trajectory when the phased array ultrasound cannula enters the aorta from the femoral artery. Balloon tamponade of the aorta becomes more precise and is performed quickly with a 30-degree field of view and up to 2.5 cm of penetration.

[0034] Figure 17 A series of side plan and two side cross-sectional views of a hollow burr screw with a central trocar that will leave a conical channel when the central trocar is removed for safe, precise, and good fixation of the ultrasound probe into the subarachnoid space. Once in place, the burr screw allows for the removal of cerebrospinal fluid from the subarachnoid space.

[0035] Figure 18 An enlarged view showing the burr device unit that houses four or more transducers to provide ultrasound information to a microcontroller that semi-autonomously controls a servo motor to guide the screw through the skull to firmly fix the screw to the bone and stop the screw once it enters the subarachnoid space.

[0036] Figure 19 Simplified side cross-sectional schematic of the human head showing Figure 10Device, i.e., an ultrasound needle including a 2 mm inner diameter needle with 64 or more elements that can characterize tumor tissue properties in contrast to normal tissue. Instrumented ultrasound needle provides information to the image to guide semi-autonomous or robotic insertion of the needle and to treat glioblastoma tumors. The ultrasound transducer generates energy at the tip of the needle near the tumor. After tumor pretreatment, the same needle allows microliter administration of various treatment modalities. After administration of the drug, the ultrasound needle tip images the tissue to determine the location of the treatment effect relative to normal brain tissue.

[0037] Figure 20 Sagittal view of the insertion site in a human skull for a combination of devices including a trephine unit with an ultrasound needle unit to carefully guide the needle into the subarachnoid space and secure the needle in place for tissue diagnosis, to map brain tissue, and to create a trajectory for the ultrasound needle into the brain. Figure 14 Figure 18 Sagittal view of the insertion site in a human skull for a combination of devices including a trephine unit with an ultrasound needle unit to carefully guide the needle into the subarachnoid space and secure the needle in place for tissue diagnosis, to map brain tissue, and to create a trajectory for the ultrasound needle into the brain.

[0038] Figure 21 Sagittal view of an ultrasound needle with a 2 mm diameter and fitting within a 3 mm to 4 mm hollow conical space within a surrounding screw providing sufficient degrees of freedom to precisely place the ultrasound needle using a high precision semi-autonomous or robotic system.

[0039] Figure 22 Schematic of a perspective view of a human body showing how an exoskeleton can be used to treat solid tumors elsewhere in the body. From laser scan data or from other imaging data such as MRI or CT scans, a three-dimensional print of the exoskeleton can be rapidly produced to fit securely and precisely with minimal movement. This will give a solid infrastructure for securing a trephine and / or ultrasound needle unit to precisely access the body and target a tumor to within 1 mm of the tumor for diagnosis and treatment with ultrasound energy and to administer therapeutic drugs with high precision to the tumor and to monitor the effects on the tumor and surrounding normal tissue.

[0040] Figure 23 Schematic of a sagittal view of a pig's decapitated head and neck used in animal research. This CT scan confirms the location of the cerebellopontine angle needle and the location of the thermistor indicated by the white arrow.

[0041] Figure 24 Sagittal view of a pig's decapitated head and neck used in animal research. This CT scan confirms the location of the cerebellopontine angle needle and the location of the thermistor indicated by the white arrow.

[0042] Figure 25 Sagittal view of a pig's decapitated head and neck used in animal research. This CT scan confirms the location of the cerebellopontine angle needle and the location of the thermistor indicated by the white arrow. Figure 24 ​Temperature versus time plot measured in the depicted pig experiment.

[0043] The present disclosure and its various embodiments can now be better understood by turning to the following detailed description of the preferred embodiments, which are presented as illustrative examples of the embodiments defined in the claims. It is expressly understood that the embodiments defined in the claims can be broader than the illustrative embodiments described below. DETAILED DESCRIPTION

[0044] Animal study:

[0045] Due to previous unsuccessful attempts to cool the brain via lumbar puncture, the cistema magna, located at the base of the brain, was chosen as the entry point for the cooling device. Due to the warm circulation of blood vessels in the spinal canal, entry through the spinal canal results in an increase in temperature of the aCSF. By entering the largest pool, the cistema magna, a 17 gauge needle can be placed in the subarachnoid space and used to circulate cooled saline out through a drain in the forehead. Using this method, initial work performed on over 50 recently deceased pigs provided promising results and encouraged in vivo testing.

[0046] For in vivo testing, our approach was to combine thermistors placed at different depths (5 mm increments) in the brain to monitor the temperature of the tissue and, thus, the effect of circulating cooled aCSF as depicted in the CT scan of Figure 24 The brain temperatures collected during the in vivo experiment prove that it is possible to cool the brain in a large animal model under general anesthesia with the inflow of warm blood into the brain. Furthermore, the brain temperature was monitored without blood flow once the sample was terminated with euthasol at 15:35. Figure 25 The graph of Figure 3 demonstrates that termination of the inflow from the heart's warm blood results in additional cooling of the brain. These results are in line with our hypothesis that it is necessary to take into account the warm gradient of incoming blood when trying to cool the brain with cooled aCSF. Figure 25 Figure 4 is a graph of data collected from four implanted thermistors monitoring the brain temperature of a pig model under general anesthesia and our proposed methodology to induce hypothermia. Each thermistor was placed in the cortex at four different depths from the surface of the brain in 5 mm increments. The horizontal bars indicate the pump speed in mL / min. The temperature dropped to 15°C within the first 10 minutes. After termination of the sample at 15:35, the temperature continued to decrease until the end of the experiment.

[0047] In contrast, this entirely new system is designed for the extreme case of an emergency situation, specifically for patients who are experiencing shock or have very little blood flow to the brain. These cases would be more advantageous because the heat from the circulating blood would be minimized, making it even easier to cool the brain and thus maximizing the time of the intervention.

[0048] The results from our in-vivo studies give us support for a way to cool the brain directly through cooling the CSF and allow for convective cooling to enhance the cooling effect in the subarachnoid space near the cortex where the neurons are located. Furthermore, since the CSF flow from the cistema magna starts at the base of the brain, the cooling of the memory loops is early. Since the circulation of the vertebrobasilar arteries is adjacent to the cistema magna, there will be cooling of the circulating blood without any vascular cannulation, causing additional cooling of the deep structures.

[0049] We have demonstrated the efficacy of the cooling system as shown in Figure 1 The most important warning is that once the needle is inserted, it must be immediately secured so as to prevent the ultrasound needle 3 from being repositioned outside the cistema magna 1. The aCSF is chilled in the cooler 7 to a temperature in the range of 1 °C to 10 °C, carried by the pump 8, through the filter 9 and into the needle 3 in the cistema magna 1. The flow of the cooled aCSF throughout the subarachnoid space 2 is very effective for cooling the brain at different levels, especially at the cortical surface where the more vulnerable neurons of the gray matter reside. In elderly patients, the subarachnoid space 2 is larger because of the natural shrinkage of the brain with age, causing the brain to be more rapidly exposed to the cooling effect, with a larger volume of aCSF in circulation. The cooled aCSF in the cistema magna 1 is in close proximity to the circulation of the basilar and Circle of Willis arteries, which will have an additional cooling effect on the central structures, especially on the brain areas that facilitate memory. Note that the cooling system can initially be chemical cooling, which is a more simplified and effective method in an emergency situation. Furthermore, if the treatment is not necessarily to cool the brain, but to change the temperature to a warmer state, then a cooler and / or warmer can be utilized in a similar system to produce the appropriate temperature for the lavage. Thermistors are provided to monitor the temperature within the subarachnoid space 2 at the exit of the aCSF 5 through the trephine 4 in the front of the skull, as well as at the entrance into the cistema magna 1. An intracranial pressure gauge monitors the intracranial pressure.

[0050] The disclosed apparatus and method provides a successful and safe way to rapidly cool the brain by using deep hypothermia to prevent brain death. The needle 3 is safely, quickly and accurately placed into the cistema magna 1 to circulate cold artificial cerebral spinal fluid (or other isotonic solution) into the intracranial and subarachnoid space 2. By lowering the temperature of the artificial cerebral spinal fluid (aCSF) and circulating it around the basilar vessels, the circulation of the brain will be cooled. Once the cooled aCSF reaches the subarachnoid space 2 through a computer controlled peristaltic pump, convection cooling will begin, especially in the posterior part of the brain, as an outlet will be made through the frontal bone for the warmer fluid to exit. As shown in Figure 1 the outlet aCSF will then be collected aseptically.

[0051] Alternatively, it will be cooled and filtered outside the body and recirculated back into the inserted needle 3 as shown in Figure 2 which will be firmly placed into the cistema magna 1. In Figure 2 the aCSF 10 is recirculated from the outlet port in the skull to the pump requires a filtration system 9 to remove infectious agents and debris from the aCSF before it re-enters the cistema magna 1. Recirculating the aCSF 10 in a sterile environment has many advantages: easier to maintain a sterile environment; more effective cooling; less aCSF required in an emergency; can create efficiencies in space and supply. The inserted needle 3 will be secured to the head and neck to a stabilizing structure as described in Figure 12 and Figure 13 to prevent the needle tip from moving within the cistema magna 1.

[0052] Figure 12 One configuration of a method to secure the needle tip after entering the cistema magna 1 is shown, including the use of an exoskeleton 24 placed on the back of the head and neck to give the ultrasound needle the proper insertion into the cistema magna 1 the security, stability and precision. The mastoid bone and / or the external ear canal will be the fixed posterior point, while a trephine screw in the frontal bone will be the fixed anterior point. A "skull cap" will be fitted like the exoskeleton 24 to give the ultrasound needle security and stability.

[0053] Figure 13 A second embodiment of securing the needle after entering into the cistema magna 1 is shown. It includes the use of a secure band placed around the forehead at the trephine, which is screwed firmly into the frontal bone 25 and the secure band travels around the upper cervical spine without causing compression injuries to the ears. The external ear canal will be used as a reference point to locate the band in the proper plane. When the needle enters the cistema magna 1, it gives the needle a stable security. Furthermore, if a servo motor system is used to semi- autonomously or automatically guide and move the needle into the cistema magna 1, it will require a stable and secure base from which it will guide the needle, such as the "skull cap" exoskeleton 24 described in Figure 12 .

[0054] The circulation of cooled aCSF in the subarachnoid space rapidly cools the entire brain, including structures at the base of the brain and gray matter on the outer surface of the brain.

[0055] exist Figure 3 In this case, a single opening is planned in the skull to allow the aCSF circulating from the subarachnoid space 2 to exit, and if the patient is supine, the opening is preferably positioned towards the frontal lobe to utilize... Figure 8 The convection cooling is shown. A semi-autonomous or robotic trephine 4 with a hollow screw is used for evacuation. Figure 18 The fluid within the cerebellomedullary cistern 1. Temperature sensor 11 provides feedback on cooling depth, cooling efficiency, and cooling rate through the same opening. A pressure sensor (not shown) will also be necessary to prevent brain damage from excessive pressure during aCSF administration. Knowing the temperature and flow rate of the fluid entering the cerebellomedullary cistern 1 and exiting the outlet point 4 will provide information on the cooling rate and cooling efficiency. Figure 8 This explains the cumulative effect of convective cooling 13 on the pumping action on the aCSF after it enters the cerebellomedullary cistern 1 and settles in the occipital region of the head while the patient is supine. Convective cooling occurs because the cold CSF is in the lower occipital region and the relatively warm CSF is facing the upper frontal lobe, in which the warmer fluid is evacuated to drain.

[0056] Therefore, the disclosed device and method successfully and safely generate deep hypothermia in the brain. Furthermore, the method also effectively, rapidly, and safely cools the brain, such as… Figure 6 The spinal cord is used to prevent post-traumatic spinal cord swelling or to protect the spinal cord from ischemic injury; the flow of cooled aCSF is diverted downwards from the cerebellomedullary cistern 1 to the lumbar region via the discharge through the lumbar puncture needle 14, thereby causing cooling of the spinal cord.

[0057] Cardiac arrest, stroke, and bloodletting can lead to brain death within 5 minutes unless the brain can be rapidly placed in a state of suspended life, giving the treating physician up to an hour or more to save the patient's life, as provided by the devices and methods disclosed herein.

[0058] The disclosed equipment includes, for example: Figure 9 and Figure 10 The described ultrasound-guided needle 3 has multiple elements configured to provide a three-dimensional ultrasound image anterior to the needle. The image and ultrasound feedback are displayed on a video monitor similar in size to a mobile phone, enabling caregivers to quickly and safely access the cerebellomedullary cistern 1 of the brain. Furthermore, the tip of the needle 3 includes, for example, […]. Figure 11The temperature-sensitive alloy shown is reshaped to prevent cutting brain tissue and to facilitate the smooth flow of aCSF through needle 3. A similarly designed needle 3 allows for semi-autonomous entry into arteries and other blood vessels, such as the femoral artery, into the body when rapid and safe access is required in an emergency.

[0059] In order to prevent brain death by rapidly cooling the brain using deep hypothermia, it is crucial to design the needle 3 to be placed safely, quickly, and accurately in the cerebellomedullary cistern 1 so that cooled artificial cerebrospinal fluid or other isotonic solutions circulate into the intracranial space and subarachnoid space 2.

[0060] Figure 5 A novel approach from the side of the neck, just below the mastoid bone 12, is shown. Gong et al. (Journal of Neurosurgery 129: 146-152, 2018) described 1008 lateral atlanto-occipital interstitial punctures, with a success rate of 98.3%. This approach offers advantages such as rapid insertion, proximity to the mastoid bone for fixation, and a high insertion success rate. Currently, this procedure is performed by neurosurgeons and neuroradiologists using fluorescein endoscopy, which is not always available in the field, emergency room, or operating room. Furthermore, errors can occur under the pressure of emergency situations, and prolonged exposure of the sharp needle tip to the cerebellomedullary cistern can cause brain damage. Therefore, a new technique for accessing the cerebellomedullary cistern 1 is clearly needed. This is addressed in this disclosure.

[0061] For caregivers or nurses, the lateral neck below the mastoid bone can be more easily located and approached. It is easily identified as... Figure 5 The bony protrusion behind the ear shown in the image does not usually require shaving the hair; it serves as a stable point for fixation, and the fixing of pin 3 can be done quickly and easily. (As shown) Figure 9 As shown, the insertion of the ultrasonic guide needle 3 provides a directional image on a handheld unit (such as a mobile phone), where visual and audio information is displayed in real time. Semi-autonomous or robotic insertion is also described. Data obtained from the tip of the ultrasonic needle 3 guides the tip of the unit to its trajectory.

[0062] Spinal cooling

[0063] Figure 6This demonstrates a novel approach to treating and / or preserving the spinal cord during direct trauma, blunt force trauma, concussion injury, ischemic trauma, explosive exposure, and surgical procedures that may compromise the blood circulation of the spinal cord. Cooled aCSF is delivered to the cerebellomedullary cistern 1, and the flow 15 of the aCSF is guided downwards along the spinal canal to induce discharge via a lumbar puncture needle 14. Similar to cooling the brain, cooling the spinal cord can be accomplished by pumping aCSF into the cerebellomedullary cistern 1 and discharging it into an outlet bottle. A technique for cooling the brain is simulated by recirculating the aCSF from the lumbar puncture needle 14 back into the cerebellomedullary cistern 1 using a series of pumps, filters, and coolers. Cooling can be initiated via the lumbar puncture needle 14 and discharged upwards through the cerebellomedullary cistern 1, depending on the hydrodynamics and the location of the spinal cord requiring cooling.

[0064] Figure 7 This involves situations where both the brain and spinal cord require simultaneous cooling. Such situations can include extensive anatomical involvement of aortic aneurysms, blast and shock trauma, and other exposures to trauma such as radiation exposure. By cooling the cerebellomedullary cistern 1, the brain and spinal cord can be cooled while the cooled aCSF is drained through drains from puncture sites in the head and lumbar region.

[0065] Prevent sharp needles from cutting the brain

[0066] To prevent the sharp tip of needle 3 from piercing or damaging the cerebellomedullary cistern 1 or other neural tissues in the brainstem, spinal cord, and cerebrum, the tip of needle 3 is made of a shape memory alloy, which changes shape with temperature as described above. Figure 11 The shape is changed within the predetermined range shown. In addition to removing the sharpness of the needle tip, the outlet can be reshaped to maximize the outflow of cooled aCSF while improving the flow pattern that could potentially damage adjacent nerve tissue. Nitinol is a deformable alloy developed by the U.S. Navy and represents a nickel-titanium alloy; it also possesses thermal memory.

[0067] Figure 11 This illustrates the concept of using a temperature-sensitive alloy such as nitinol at the cutting tip of the needle. After the sharp needle 21 penetrates into the cerebellomedullary cistern 1, the needle axis must be firmly fixed in that defined position. Removing the cannula and applying cooled aCSF through the needle axis causes the cutting tip to reform into a blunt tip 22 without a sharp edge. If the pump is rapidly applied to a higher volume, it is important to design a new shape for the tip of the needle axis to produce a gentle dispersion of aCSF as it enters the cerebellomedullary cistern 1. This could require an open tip 23 or other shapes determined by computer simulation and modeling.

[0068] When using a similarly designed needle 3 to rapidly enter large blood vessels such as the femoral artery, the phased array cannula 19 within the tip of the needle 3 delineates various tissues until the needle 3 enters the artery, while the nurse uses... Figure 9 The handheld video and audio unit shown is used to quickly guide the tip and needle 3 into the blood vessel. Figure 15 The target site of the femoral artery 28 is shown, along with various tissues and vessels that may cause confusion during insertion. A semi-autonomous unit 26 is fixed to an anatomical structure that provides stability and fixation for needle insertion into the femoral artery 28. Doppler signals inform the difference if confusion arises regarding the distinction between arteries and veins. Once the needle tip 3 is in the artery, if any prolonged time is required, the temperature-sensitive alloy tip 3 changes shape at the higher temperature of the arterial blood to blunt any sharp surfaces, thus preventing damage to the artery. Figure 11 As shown. The phased array cannula 16 extends upward along the aorta to identify the blood circulation of the surrounding abdominal tissues and the vessels leading to structures such as the kidneys, spleen, pancreas, liver, heart, and other organs, as shown. Figure 16 As shown. The phased array element has a 30-degree field of view, can penetrate forward up to 2.5 cm, and has the following characteristics: Figure 10 The real-time 3D imaging shown. Figure 16 The trajectory of the phased-array ultrasound cannula as it enters the aorta from the femoral artery 28 is shown. The cannula has a 30-degree field of view and a penetration depth of up to 2.5 cm, providing real-time three-dimensional images of its detachment from the aortic vascular branches. In the event of life-threatening bleeding, aortic balloon tamponade 29 can be performed more precisely and rapidly.

[0069] Figure 10 This demonstrates the effective three-dimensional space in front of 64 or larger elements within a 2 mm inner diameter cannula configured for phased array imaging. Ultrasound data covers a 30-degree field of view and a penetration depth of up to 2.5 cm². Phased array imaging using multiple ultrasound elements is used throughout the medical industry. Volcano's system with a catheter-based ultrasound system features Angio+™ quantitative coronary artery analysis, which automatically calculates lumen size and stenosis in real time. Interson has commercially produced small transducer systems with commercially available hardware, using their built-in electronics for applications in cardiac disease.

[0070] Motorized insertion of needles

[0071] Semi-autonomous or robotic technologies have been widely practiced for decades and are used for navigation in vehicles such as self-driving cars. Based on radar, camera data, and GPS information, "self-driving" cars use artificial intelligence to program the vehicle to safely navigate its route from home to work. Similarly, we utilize three-dimensional ultrasound information from the needle tip and use artificial intelligence to program servo motors to guide the needle safely through the skin, fat, muscle, tendons, and blood vessels to reach the cerebellomedullary cistern. Once in the cerebellomedullary cistern, the needle automatically locks in place to prevent damage to nerve tissue. This requires specialized software development, all of which has been done in other industries. The novelty of this invention lies in the application of custom-developed software to enable semi-autonomous or robotic needle insertion with several orders of magnitude greater precision than that of self-driving cars (approximately a fraction of a millimeter within the target area).

[0072] As disclosed in Mathiassen et al.'s "Visual Servoing of a Medical Ultrasound Probe for Needle Insertion," presented at the 2016 IEEE International Conference on Robotics and Automation (May 16-21, 2016), ultrasound-guided transdermal needle insertion is routinely performed in hospitals. Automating these procedures increases placement accuracy and reduces the time spent by healthcare professionals. A crucial step in automation is estimating needle orientation and positioning in the ultrasound image. One way to estimate needle orientation and positioning is to align the needle with the image plane of the ultrasound probe. Even with precise measurements and calibrations of both the needle and probe, alignment with the plane is challenging. Using a robot to perform visual servoing to move the ultrasound probe and align the probe's image plane with the needle solves this alignment problem. This method segments the needle and updates a set of visual features based on a model of the needle. A state machine is used to keep track of the alignment process, and different visual features are used to control the probe in different states.

[0073] Methods, algorithms, and devices exist in the art that use images acquired from cameras to guide the steering, braking, and acceleration of a vehicle. For example, see U.S. Patent Application 15 / 413568, “Autonomous Driving Control Device,” and U.S. Patent 9566983, “Control Arrangement Arranged To Control An Autonomous Vehicle, Autonomous Drive Arrangement, Vehicle and Method,” both of which are incorporated herein by reference. In our technology, instead of using images from a camera, we use images from our ultrasound probe. Instead of controlling the movement of the vehicle, we control the movement of the probe. Generally, the concepts and methods are similar. The algorithms will be different to adapt to the use of different types of images and the control of different types of actuation mechanisms. The methods for making these adjustments are within the scope of ordinary art. Numerous patents have been published concerning the use of ultrasound images as feedback to control medical devices. Specifically, U.S. Patent 8,343,050, "Feedback in Medical Ultrasound Imaging for High Intensity Focused Ultrasound" (incorporated herein by reference), describes the use of ultrasound imaging to detect and monitor small changes in tumor tissue caused by the application of high-intensity focused ultrasound (HIFU) to the tissue. The image is used as feedback to control the focus, intensity, and duration of the HIFU. In our case, we use the same ultrasound imaging technique as feedback to control probe movement. The algorithm is adapted to control a servo motor instead of the HIFU. The basic principles and methods are the same.

[0074] The motorized inserter used for the needle 3 to enter the cerebellomedullary cistern 1 requires a microcontroller 38 with artificial intelligence to control a servo motor 39. The servo motor 39 is a rotary or linear actuator that allows for precise control of angular or linear position, speed, and acceleration. Figure 14 As shown, it includes a suitable motor coupled to a sensor for positioning feedback. Figure 14System 26 is depicted, which semi-autonomously or robotically inserts a needle 3 equipped with a phased-array ultrasound cannula, the phased-array ultrasound cannula having an ultrasound data feedback unit 37 connected to a microcontroller 38 and a microcontroller-guided servo motor 39. Once the medical expert sets the trajectory of the needle 3 on its path to the target (cerebellomedullary cistern 1), the ultrasound data feedback unit 37 guides the servo motor 39 in real time to insert the needle 3. It is securely attached to a fixation device at the site, such as a "cranial cap" shaped like an exoskeleton 24 or similar. Figure 12 and Figure 13 The described similar device, and it depends on, for example, Figure 9 and Figure 10 The phased array ultrasound system 16 described herein receives information from the ultrasound data feedback unit 37. The servo motor inserter 26 facilitates the rapid, accurate, and safe insertion of the needle 3 into the cerebellomedullary cistern 1 in emergency situations. Figure 9 A device is shown for guiding a needle through the skin to reach the cerebellomedullary cistern 1 using a unique adapter at the tip of the needle via known techniques. This is achieved by using a 2mm diameter cannula within a cutting needle (17 gauge) 16. Figure 10 The 64 or more ultrasound elements 19 shown are used to generate a phased array ultrasound image field 20. A three-dimensional image is displayed in real time on a handheld portable monitor 18 using raster graphics. An interface unit 17 converts the ultrasound data into imaging information to be displayed. Visual and auditory feedback provided by the monitor 18 assists in inserting the needle into the cerebellomedullary cistern 1. Furthermore, the shape of the cerebellomedullary cistern 1 can be delineated for easier and more precise insertion. (See below for more details.) Figure 12 and Figure 13 In more detail, once the needle 3 is secured to a stable site, the cannula 16 is removed from the cerebellomedullary cistern 1 to allow for the administration of cooled aCSF. In the case of a phased array needle inserted into the femoral artery, the cannula 16 can be guided into the aorta to visualize the numerous vascular branches within the aorta.

[0075] Figure 22 This illustrates how the exoskeleton 36 can be used to treat solid tumors elsewhere in the body, such as in the breast. A rigid exoskeleton can be rapidly 3D printed based on laser scan data or other imaging data such as MRI or CT scans, allowing for a secure and precise fit to the entry or manipulation site with minimal movement. This provides a solid structure for securing the trephine unit 33 and / or the ultrasonic needle 3 to precisely enter the body and pinpoint the tumor 34 to within 1 mm of its location, enabling diagnosis and treatment with ultrasonic energy, precise administration of therapeutic drugs to the tumor 34, and monitoring of its effects on the tumor and surrounding normal tissue.

[0076] Figure 23 This demonstrates how to securely fasten the device to the breast to provide stability and precision.Figure 22 The exoskeleton 36 is then used. The ultrasonic needle 3 is then precisely guided to within 1 mm of the tumor 34 to diagnose the tissue and precisely treat the tumor 34 without damaging the surrounding normal tissue.

[0077] When needle 3 is inserted into the femoral artery, the phased array ultrasound system will provide anatomical information to distinguish the femoral artery from the femoral vein. Furthermore, if the femoral pulse cannot be felt, the anatomical information from the ultrasound system will better pinpoint the location of the femoral artery. The semi-autonomous ultrasound needle unit 14 to be inserted into the femoral artery also needs to... Figure 15 The unit shown is fixed, in this case, to the inguinal ligament and / or bony prominences in the exoskeleton configuration.

[0078] Methods and apparatus for safe and rapid insertion of trephine through the skull:

[0079] To create an exit point in the forehead for the cooling fluid to exit the subarachnoid space 2 during aCSF irrigation to cool the brain, drilling into the bone in the skull using a trephine must be performed safely, quickly, bloodlessly, and precisely by a single healthcare professional. This unit must be independent, comprising a transducer in a “box” and a semi-autonomous or robotically driven insertion device, as described in “Needle Insertion Method” 26, which will be attached to the area of ​​the frontal bone. A “screw” 30 comprises a hollow shaft with a cannula 31, within which a screw with an inner diameter of 3 mm to 4 mm is carefully screwed into the skull. Information received from the transducer within device 26 controls the semi-autonomous or robotic insertion of the screw 30 through the bone and securely into the subarachnoid space 2. Figure 17 A hollow trephine screw 30 with a central cannula 31 is shown, which, when the cannula 31 is removed, leaves a conical channel 32 for safe, precise, and well-secured placement into the subarachnoid space 2. Once in place, the trephine screw 30 allows cerebrospinal fluid to be removed from the subarachnoid space.

[0080] The insertion method for the semi-autonomous trephine unit includes the following: After selecting an entry point (typically on the upper forehead near the hairline), an incision is made with a scalpel along the Kraissl line in a natural skin fold, from the skin down to the subcutaneous tissue covering the frontal bone. Maintaining sterility, an anesthetic containing a vasoconstrictor is injected into the skin, and the incision length is between 1.0 mm and 1.5 mm. A self-holding retractor is inserted into the wound to provide stability and hemostasis. A box unit 26 and screws 30 are inserted into the opening and secured to the retractor. Semi-autonomous or robotic insertion is activated and carefully guided through the bone into the subarachnoid space 2. Ultrasound data is obtained from four or more transducers 40 within the trephine "box" attached to the scalp. A microcontroller 38 with artificial intelligence guides a servo motor 39, which in turn screws the trephine into the skull. Figure 18 The final configuration, as depicted, is very stable and moves via screws in the frontal bone.

[0081] The screw 30 in the frontal bone is rigidly attached, fairly stable, and well-fixed. It serves as a point where the headband is brought to the back of the head and attached to two or three points posteriorly to provide greater stability during insertion of the ultrasonic needle into the cerebellomedullary cistern, as... Figure 13 What is depicted.

[0082] At the end of the procedure, screw 30 can be removed under local anesthesia. If necessary, bone wax is placed in a small 3 mm to 4 mm opening, and a single suture is placed through the skin. Because the incision is made on the Kraissl suture, there is minimal scarring, as the incision is made within a natural skin fold.

[0083] Furthermore, because it cools the central function in the brain by creating an exit port, the disclosed methods and apparatus can be used in other brain operations, including surgery for epidural hematomas, surgery for subdural hematomas, and stereotactic intracranial surgery.

[0084] Therefore, this article presents a method of combining ultrasonic needle 3 with trephine 33 to treat intracranial brain tumors, especially glioblastoma. Figure 18 The diagram shows a trephine unit 33, which houses four or more transducers to provide ultrasound information to a semi-autonomous or robotically controlled servo motor, thereby guiding the screw through the skull to secure it to the bone and stopping the screw once it enters the subarachnoid space 2.

[0085] A novel approach to diagnosing, locating, and managing glioblastoma:

[0086] Glioblastoma (the most common intrinsic brain cancer) challenges early diagnosis and treatment. From diagnosis using conventional imaging and brain biopsy to the inevitable death of patients within 4 to 16 months, these patients often undergo neurosurgery, radiation, and chemotherapy with little hope of a cure. We possess the technology and expertise to characterize and diagnose the disease, perhaps without the need for a formal biopsy of the tissue to study tissue features from data using ultrasound. The proposed method involves a minimally invasive insertion of an ultrasound needle into the skull and subarachnoid space to scan the brain with a 30-degree field of view and a depth of up to 2.5 cm. Ultrasound data from the needle tip will provide three-dimensional imaging of the tumor and will then be used to semi-autonomously or robotically insert the needle tip within 1 mm of the target tissue. This requires the precision and development of a servo-controlled device to trephine 33 through the skull and guide the ultrasound needle 3 to the target tissue.

[0087] Current existing technologies for ultrasound imaging of the brain involve using a transducer on the scalp and transmitting energy through the skull. Low-frequency transducers have advantages in transmitting energy through tissues of the scalp and bone, but they offer lower resolution. To achieve high-resolution imaging at the cellular and / or tissue level, the ultrasound transducer must be closer to the object and have high-frequency imaging capabilities. This presents a dilemma. Therefore, an ideal ultrasound design would have a non-invasive device that penetrates to the site of disease using a high-frequency transducer. This can be accomplished by making the opening of the trephine 33 through the skull small enough for minimal invasiveness and by using an ultrasound unit designed to be positioned within the contour of the needle 3. Furthermore, a semi-autonomous or robotically powered system could be used to precisely insert the ultrasound needle 3 into the soft tissues of the body. Recent basic laboratory studies by Sheehan et al. reported the positive effects of using ultrasound radiation to enhance the drug's effect on the death of glioblastoma cells in cultures (Kimball Sheehan et al. Investigation of tumoricidal effects of sonodynamic therapy in malignant glioblastoma brain tumors. J. Neuro-Oncology. 148, 9-16, 2020).

[0088] The above discloses the use of an ultrasonic needle 26 and a semi-autonomous or robotic trephine 33, which goes beyond the initial purpose of cooling the brain in cases of brain death. This approach is based on sound, as it utilizes elements in the tip of the needle 3 used for imaging; the sound is programmed to generate energy from the same transducer in the same tip of the needle 3. This method for treating glioblastoma of the brain relies on the close relationship between the semi-autonomous or robotic ultrasonic needle 26 and the semi-autonomous or robotic trephine 33, which are engaged together to form a unique, precise, and stable platform. The design and characteristics of the ultrasonic needle 26 and the trephine 33 are described above. The application of this technology creates a new approach for the diagnosis, localization, and management of glioblastoma of the brain.

[0089] Furthermore, the ultrasound needle comprises at least 64 elements within a 2 mm diameter cannula at the needle tip, defined as less than 0.1 mm in diameter, with a 30° field of view and a depth of up to 2.5 cm. It is capable not only of imaging the shape and size of tumors but also of revealing specific tissue features as ultrasound passes near or within tumors and through normal tissue. Therefore, tissue diagnosis can be performed using ultrasound alone. After the semi-autonomous or robotic insertion of the hollow screw 30 is lowered to the level of the subarachnoid space 2, the cannula 31 of the screw 30 is removed and replaced with an ultrasound needle 3 surrounded by its own semi-autonomous or robotic unit 26. These two units act as a single unit and are securely attached, thus providing extreme accuracy and fixation as the needle 26 is advanced deeper into the cranial cavity. Figure 19 It shows Figure 10 The device used comprises an ultrasonic needle 3 with a 2 mm inner diameter needle 3, having 64 or more ultrasonic elements that characterize tumor tissue in contrast to surrounding normal tissue. The ultrasonic elements provide information to an image, guiding a semi-autonomous or robotic insertion device 26 of the needle 3 through a semi-autonomous or robotic trephine 33, and treating the glioblastoma 34. An ultrasonic transducer generates energy at the tip of the needle 3 near the tumor 34. After pretreatment of the tumor 34, the same needle 3 will allow for micro-level control of various treatment modalities. After drug administration, the ultrasonic needle 3 can then image the tissue to determine the location of the treatment effect.

[0090] Ultrasound (US)-guided biopsy is a routine medical procedure performed in clinical practice. This task can be performed by robotic systems to improve the accuracy of the procedure and thus enhance patient safety. Both robotic and human manipulation greatly benefit from real-time needle localization in ultrasound images. This information guides the robot or expert to the correct target point, avoiding critical structures. In "Real-Time Biopsy Needle Tip Estimation in 2D Ultrasound Images," presented by Mathiassen et al. at the IEEE International Conference on Robotics and Automation (May 6-10, 2013), a needle localization method capable of extracting needle orientation and tip position in real time from B-mode ultrasound images was disclosed. Results showed improvements in localization accuracy compared to previous work in the literature.

[0091] As disclosed in Mathiassen, “Robust Real-Time Needle Tracking in 2-D Ultrasound Images Using Statistical Filtering,” IEEE Transactions on Control Systems Technology, 2017, 25(3) 966-978, percutaneous image-guided tumor resection is a minimally invasive surgical procedure for treating malignant tumors using a needle-shaped resection probe. Accuracy is improved and the execution time of the procedure is reduced by using a robot to automatically insert the needle. Extracting the needle tip position from the ultrasound (US) image verifies that the needle is not approaching any restricted areas (e.g., major blood vessels and ribs) and is also used as a direct feedback signal for the robot's needle insertion. Methods for estimating the needle tip have previously been developed, combining a modified Hough transform, image filtering, and machine learning. Methods that introduce dynamic selection of regions of interest in the ultrasound image and filter the tracking results using a Kalman filter or a particle filter are also known. The results show that accuracy is significantly improved compared to previous automated methods, with errors reduced by more than 85% to 95%. The method operates in real-time at a frame rate of 35.4 frames / s. The improved robustness and accuracy make the disclosed algorithm applicable to autonomous or robotic surgical systems for needle insertion.

[0092] Figure 20 yes Figure 19 A magnified view of a portion showing the insertion site, and showing... Figure 17 and Figure 19The combination of devices includes a trephine unit 33 with an ultrasonic needle unit 26 to carefully guide the ultrasonic needle 3 into the subarachnoid space 2 and fix it in place for tissue diagnosis, mapping of brain tissue and forming a trajectory for the ultrasonic needle 3 to enter the brain.

[0093] Figure 21 This demonstrates how the design allows for the precise orientation and guidance of the ultrasound needle 3 to its target location at the glioblastoma tumor 34. Because the ultrasound needle 3 has a diameter of 2 mm and is fitted within a 3 mm to 4 mm hollow conical space within the surrounding stabilizing screw 30, the precise placement of the ultrasound needle 3 can be accurately performed using a semi-autonomous or robotic system 26.

[0094] Because the hollow core within screw 30 is shaped like a cone, there will be some gaps of a 2 mm diameter needle within the 3 mm to 4 mm hollow screw trephine. Therefore, control using a semi-autonomous motor or robotic motor allows needle 3 to extend its range to cover areas greater than 30°. Imaging the tissue immediately in front of the ultrasound needle to a depth of up to 2.5 cm will depict the shape and size of the tumor. Furthermore, because tissue density can be determined using ultrasound, it will be possible to diagnose glioblastoma cells from normal tissue. To confirm the ultrasound diagnosis, a needle biopsy can be performed using needle 3 for confirmation.

[0095] If it is decided to guide the needle 3 deeper into the brain tissue using semi-autonomous or robotic control and ultrasound information, it can be slowly and precisely placed at or even within the boundaries of the tumor 34. The transducer can then be programmed to generate ultrasound energy at the tip of the needle 3 into the tumor 34. Chemotherapy agents, immunotherapy, or other forms of administration can be delivered via the needle tip 3 in well-controlled, small microliter volumes. The effects of the injected tissue can be determined by using ultrasound imaging to look for abnormal tissue responses. An intracranial manometer (not shown) indicates the presence of swelling in tissues that could cause an increase in intracranial pressure. If necessary, brain-operated hypothermia can then be applied to cool the brain and prevent swelling.

[0096] Semi-autonomous or robotic insertion of ultrasonic needles:

[0097] Semi-autonomous or robotic insertion of the needle into the cerebellomedullary cistern is accomplished using a servo-controlled motor guided by information obtained from 64 elements within the tip of needle 3. For example... Figure 10 As shown, the information will have a three-dimensional space with a range of 30 degrees and a depth of up to 2.5 cm. Artificial intelligence with self-learning algorithms... Figure 14 The microcontroller 38 in device 26 provides machine learning. Semi-autonomous or robotic insertion and servo-controlled motor enablement are described under “Motorized Insertion of Needles”.

[0098] Semi-autonomous or robotic insertion of screw trephine:

[0099] The semi-autonomous or robotic insertion of the screw trephine 33 through the skull into the subarachnoid space will utilize a servo-controlled motor (not shown), guided by information received from four or more transducers in unit 26 placed on the scalp. Figure 18 The information includes bone thickness, the interface between the dura mater and arachnoid mater, and ultrasound data of the subarachnoid space 2 containing cerebrospinal fluid. Once the controller determines the appropriate interface for the hollow-hole screw 30 with cannula 21, the fixation of the screw 30 within the bone is completed automatically. Semi-autonomous or robotic insertion and servo-controlled motor activation are described under "Motorized Insertion of the Needle".

[0100] Many changes and modifications can be made by those skilled in the art without departing from the spirit and scope of this embodiment. Therefore, it must be understood that the embodiments shown are illustrated for illustrative purposes only and should not be construed as limiting the embodiments as defined by the presented embodiments and their various embodiments.

[0101] Therefore, it must be understood that the illustrated embodiments are for illustrative purposes only and should not be construed as limiting the embodiments defined by the presented claims. For example, although the elements of the claims are set forth below in a certain combination, it must be clearly understood that the embodiments include other combinations of fewer, more, or different elements, which are disclosed above even if not originally claimed in such combinations. The teaching of combining two elements in a claimed combination is further understood to also allow claimed combinations in which the two elements are not combined with each other, but can be used alone or in combination in other ways. Any omissions of disclosed elements in the embodiments are expressly covered within the scope of protection of the embodiments.

[0102] The terms used in this specification to describe various embodiments should be understood not only in their ordinary meaning but also, by specific definition, to include structures, materials, or actions that go beyond their ordinary meaning in this specification. Therefore, if an element can be understood to include more than one meaning in the context of this specification, its use in the claims must be understood to be general to all possible meanings supported by this specification and the terms themselves.

[0103] Therefore, the terms or elements of the presented claims are defined in this specification not only to include combinations of elements literally stated, but also to include all equivalent structures, materials, or actions used to perform substantially the same function in substantially the same manner to obtain substantially the same result. Thus, in this sense, it is contemplated that equivalent substitutions of two or more elements may replace any one of the elements in the presented claims, or a single element may replace two or more elements in the claims. While elements may be described above as functioning in certain combinations and even initially claimed in this way, it should be clearly understood that in some cases, one or more elements from the claimed combination may be removed from the combination, and the claimed combination may involve sub-combinations or variations thereof.

[0104] As will be apparent to those skilled in the art, any non-substantial modifications now known or later designed from the claimed subject matter are explicitly considered equivalent to the scope of the claims. Therefore, any obvious substitutions now known or later known to those skilled in the art are limited to the scope of the defined elements.

[0105] The claims are therefore to be understood to include the content specifically shown and described above, the conceptually equivalent content, the content that can be obviously substituted, and the content that substantially incorporates the basic ideas of these embodiments.

Claims

1. A device for preventing brain death, comprising: A needle having a tip for piercing a patient's skin; A phased array of ultrasonic elements for generating ultrasonic images, the phased array being disposed at the tip of the needle; and An ultrasound imaging system, in a lightweight handheld monitor with audio capability, communicates with the phased array in the tip of the needle to generate images of all tissues from the skin surface down to the target tissue with a penetration of up to 2.5 cm or greater within a field of view of at least 30 degrees or greater.

2. The device according to claim 1, used to prevent the sharp needle tip from moving and damaging the brain, wherein, The needle tip has a sharp cutting shape for entry into the cerebellomedullary cistern of a patient, and wherein the needle tip comprises a deformable alloy to respond to temperature changes when cooled aCSF enters the needle, thereby causing a shape change to a blunt edge and a blunt tip to avoid damage to adjacent brain tissue of the cerebellomedullary cistern.

3. The device according to claim 2, for preventing brain damage caused by the high fluidity of aCSF, wherein, The tip of the needle has a sharp cutting shape, and wherein the tip of the needle is made of a deformable alloy to respond to temperature changes when cooled aCSF enters the needle, causing a shape change that allows the aCSF to disperse gently rather than a strong, direct flow of fluid that could damage the cerebellomedullary cistern and the adjacent brain tissue.

4. The device of claim 1, for simplifying rapid insertion by a single person, the device further comprising: A semi-autonomous unit having a microcontroller with artificial intelligence; An ultrasound imaging system, housed in a lightweight handheld monitor with audio capabilities, communicates with the phased array in the tip of the needle to generate images of all tissues from the skin surface down to the target tissue; as well as A servo-controlled motorized inserter, the motorized inserter being controlled by the ultrasound imaging system to guide the needle into the patient's cerebellomedullary cistern using the ultrasound image data.

5. The device according to claim 1, further comprising: The cannula, disposed in the tip of the needle, and An ultrasound imaging system, housed in a lightweight handheld monitor with audio capabilities, communicates with the phased array in the tip of the needle to generate images of all tissues from the skin surface down to the target tissue; as well as The phased array of the ultrasound element is arranged in the cannula and further includes a semi-autonomous or robotic unit that communicates with the ultrasound imaging system to guide the phased array cannula into the arterial circulation of the femoral artery of the pleurally bleeding patient for rapid and accurate placement in the femoral artery, wherein the cannula assists in selective balloon tamponade of the aortic circulation or its branches.

6. The device according to claim 1, utilizing an in-tip phased array ultrasound element, for locating, biopsiing, and treating glioblastoma or other systemic brain tumors, wherein, The phased array of the ultrasound element generates energy for therapeutic modulation of the tissue, and wherein the ultrasound imaging system identifies specific tissue features of solid tumors that contrast with normal tissue located elsewhere in the brain or patient's body.

7. The device of claim 1, for locating, diagnosing, and treating tumors in other parts of the body, including breast, liver, pancreas, and other tumors, the device further comprising an exoskeleton and an ultrasound-guided semi-autonomous trephine unit, the exoskeleton being capable of being positioned at an operating location on the patient's body; the ultrasound-guided semi-autonomous trephine and / or unit being configured to allow the needle to be precisely and stably fixed relative to the exoskeleton at the operating location during the guidance of the needle's entry.

8. The device according to claim 7, wherein, The shape of the exoskeleton is defined using a three-dimensional surface scan of the operating position, such that the exoskeleton is securely and precisely fitted to the operating position with minimal movement relative to the operating position for precise and stable fixation of the trephine unit and / or needle unit, thereby enabling precise calibration and entry into the vicinity of the tumor within 1 mm to diagnose and treat the tumor using ultrasound energy, administer therapeutic drugs to the tumor, and / or monitor the effects of drugs on the tumor and surrounding normal tissues.

Images