Apparatus and method for monitoring intracranial changes in a patient

Abstract

A computer system and method for continuously monitoring intracranial blood flow velocity in a patient supported by artificial ventilation using signals from an array of ultrasound transducers configured to be externally attached to the patient's head to monitor blood flow within intracranial vessels. The system includes: a database for storing signals transmitted and received from the ultrasound transducer array, configured to cover an area on the patient's head corresponding to the intracranial vessels to be measured; and a processor with instructions for: receiving signals from the ultrasound transducer array into the computer system; calculating blood flow velocity based on the Doppler frequency shift of the signals from the ultrasound transducer array; aggregating the blood flow velocity with signals simultaneously measured from one or more patient monitoring devices; and calculating optimized settings for the patient monitoring devices based on the blood flow velocity values.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority and benefit to U.S. Provisional Application No. 63 / 585,013, filed September 25, 2023, entitled “Apparatus and Method to Monitor Intracranial Alterations in Ventilation / Perfusion in Newborn Critical Care Including the Retina,” the description and claims of which are incorporated herein by reference.

[0003] Statement regarding federally funded research or development

[0004] not applicable.

[0005] Names of the parties to the joint research agreement

[0006] not applicable.

[0007] By incorporating material submitted in compact format through citations

[0008] not applicable.

[0009] Statements previously disclosed by the inventors or co-inventors

[0010] not applicable.

[0011] Copyright protected materials

[0012] not applicable. Background Technology

[0013] Since 1942, retinopathy of prematurity (ROP) has been associated with oxygen toxicity. At that time, retrolental fibrosis (RLF) was thought to be caused by oxygen toxicity, leading to vasoconstriction, which in turn caused retinal ischemia and fibrosis. Similarly, hypoxia can cause ischemic damage and RLF. Angiogenic factors are released during retinal hypoxia, leading to severe ROP and vitreous angiogenesis.

[0014] To prevent ROP, strict control of oxygen delivery and maintenance of intravascular oxygen saturation (SpO2) within limits are crucial. However, there is no consensus among professionals, professional organizations, and academic institutions. Since 1990, SpO2 limits have been observed in clinical practice between approximately 87% and 92%, then from around 2006 to 2018, the limits were between 83% and 92%. Currently, there are vendor differences in application and monitoring, with limits ranging from approximately 85% to 92%. Despite these practice differences, the observed results are comparable to state-mandated CPQCC / VON data—in fact, in 1998, the incidence of stage 3 or higher ROP was 0.6% in 163 patients weighing less than 1250g.

[0015] Analysis of ventilatory complications revealed significant differences in complications across different ventilation modes. Experience with triggering ventilation using an electrical system that initiates the ventilator cycle at the start of inspiration and terminates it on voluntary expiration showed a significant reduction in complications such as pneumothorax, intraventricular hemorrhage, and recurrent respiratory arrest (ROP). However, a multicenter European study (by Baumer et al.) using a pneumatic triggering system revealed an exacerbation of complications. However, the European study did not terminate the ventilator cycle on voluntary expiration. Consequently, transthoracic pressure (Paw) increased, leading to impaired venous return and increased intracranial pressure.

[0016] Treatment of preterm infants includes ventilatory support. A common mode of assisted ventilation is high-frequency ventilation (HFV). Recurrent obstructive pulmonary disease (ROP) is a preterm complication. The probability of ROP is associated with positive pressure ventilation (PAP) that significantly alters ventilation / perfusion (V / Q), such as high-frequency ventilation (HFV) in preterm infants. Assisted PAP in infants can affect the heart and lungs, as these organs are interdependent. Assisted PAP is known to sometimes impair venous return in infants. This is exacerbated by the presence of patent ductus arteriosus (PDA) in newborns (which causes hypoxic blood to shun from the venous circulation into the arterial circulation or into the lungs, both of which increase the shunting rate). It has been observed that aggressive ventilation modes such as HFV increase intrathoracic pressure due to the delivery of positive airway pressure to the lungs via HFV, compared to airway pressure in the lungs without HFV at ambient pressure. Furthermore, positive pressure ventilation (e.g., HFV) eliminates the natural cyclical fluctuations in intrathoracic pressure, which significantly reduces venous return compared to natural intrathoracic pressure. Because HFV treatment impairs venous return, blood flows backward into the brain, leading to increased intracranial pressure and intraocular pressure (IOP). Increased IOP can cause insufficient retinal perfusion, resulting in recurrent intraocular pressure (ROP). Abnormal IOP can be, for example, exceeding approximately 20 mmHg. Infants receiving HFV have a 30% increased risk of ROP, while infants not receiving HFV have only a 6% risk. IOP is a current measure of intracranial pressure, but not a continuous measurement.

[0017] Preterm infants have small blood vessels, with vessels only about 1200 gm or less, and high pulmonary venous ventilation (HFV) increases intrathoracic pressure at a rate ranging from 5 to 15 Hz or 900 breaths per minute. This increased intrathoracic pressure also increases pressure on the brain, leading to a ventilation (“V”)-perfusion (“Q”) V / Q mismatch. V / Q mismatch can be further explained as follows: To achieve oxygenation goals, different methods are used in assisted ventilation to increase intrapulmonary pressure (Paw): positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), inspiratory time (IT), and frequency—all of which affect the peripheral vascular system and adjacent blood flow in preterm infants. The extent to which a vascular chamber is affected depends on the amount of blood in that chamber (blood volume)—typically 80 to 100 ml / kg. However, this amount can vary significantly depending on perinatal conditions at delivery and placental transfusion to the infant (many factors such as maternal blood pressure, anesthesia, hemorrhage, rapid delivery of very small infants, etc.). Therefore, any excessive pressure on the lungs from assisted ventilation will affect the vascular system, thereby hindering venous return from the brain, leading to reduced retinal perfusion and consequently ROP. Thus, a method for monitoring intracranial blood flow in very low birth weight infants is needed. Besides ROP, other harmful events may occur, such as intraventricular hemorrhage. Similarly, any intracranial lesion can affect brain tissue perfusion.

[0018] It is speculated that similar effects are now being observed in high-frequency ventilation (HFV). These harmful intracranial factors are difficult to measure or monitor. Retrospective studies have shown an increased probability of severe recurrent pulmonary artery disease (ROP) in patients receiving HFV. However, other factors contributing to tissue hypoperfusion were not analyzed: disease severity, use of positive inotropic agents, persistent hypotension, etc.

[0019] Retinologists measure intraocular pressure (IOP) in premature infants as a reflection of intracranial pressure (ICP). Currently, these intraocular measurements are not continuous. In one embodiment of the invention, blood flow velocity and its changes in the premature infant's brain are measured and correlated with the premature infant's IOP, without directly measuring IOP using a non-invasive tonometer. The "normal value" is approximately 14.9 + / - 4.5 mmHg. Since we intend to measure IOP before applying HFV, approximately 20% of the variation will be significant. Below is a table of approximate IOP for premature infants, where age is expressed as gestational age / pregnancy age.

[0020] Table 2 – Intraocular pressure (P10 to P90) based on gestational age.

[0021]

[0022] PCA: Gestational age in weeks; IOP: Intraocular pressure.

[0023] The following systems and methods are useful for detecting changes in intracerebral hemodynamics to provide output signals to apply ventilation pressure to the lungs, thereby reducing increases in venous and intraocular pressure and thus reducing the risk of ROP, and / or for determining multiple system outputs in real time and accurately, thereby informing patient caregivers of any mismatch between ventilator settings and the patient's physiological safety parameters at each intervention adjustment. One aspect of the invention provides a system and method for monitoring and displaying such dynamic interactions of the V / Q system to objectively provide care.

[0024] This technology is feasible and, as demonstrated by non-invasively applying sensors to the head of a preterm infant at an anatomical location above the anterior fontanelle of the skull, it can display deep blood flow and pressure. One aspect provides continuous display and monitoring of blood flow velocity.

[0025] This article describes a system for non-invasive and, when necessary, continuous monitoring of the cerebral hemodynamics of preterm infants using an ultrasound sensor. Cardiopulmonary support strategies are employed when ventilating extremely low birth weight infants susceptible to recurrent op-occurrence (ROP), which can lead to blindness. A method for monitoring hemodynamic changes within the brain is provided to guide the application of ventilation pressure to the lungs to reduce increases in venous and intraocular pressure, thereby reducing the risk of ROP. According to one aspect, a technique is designed to non-invasively monitor deep blood flow in the head of preterm infants with an open anterior fontanelle at a location covering the superior sagittal sinus using an ultrasound sensor on the exterior of the skull, thereby measuring changes in blood flow within the superior sagittal sinus, venous blood flow within the sinus, and blood flow in adjacent arteries, as well as measured blood pressure. Another aspect provides a method for continuously measuring cerebral blood pressure by non-invasively applying a sensor to the fontanelle of a preterm infant. Existing technology

[0026] Note that the following discussion involves multiple publications by authors and publication years, and some publications should not be considered prior art to this invention due to their recent publication dates. The discussion of such publications herein is intended to provide a more complete background and should not be construed as an admission that such publications are prior art for patentability determination purposes. Summary of the Invention

[0027] One embodiment of the present invention provides an apparatus for noninvasively determining intracranial blood flow velocity within the superior sagittal sinus, wherein the apparatus is configured to cover an area on an infant's head corresponding to the infant's fontanelle, wherein the apparatus includes: an ultrasound transducer housing configured to attach to the infant's head and including a transducer array; at least one of a monitor and an alarm device; a controller communicatively connected to at least one of the monitor and the alarm device and the transducer, the controller being configured to receive information from the ultrasound transducer relating to the velocity of blood flow within the superior sagittal sinus below the fontanelle below the transducer's location; and to predict an increase in intracranial pressure based on changes in the velocity of blood flow measured against the superior sagittal sinus.

[0028] Another embodiment of the present invention provides a method for an apparatus configured to monitor intracranial blood flow velocity within the superior sagittal sinus, wherein the apparatus is configured to cover an area on an infant's head corresponding to the infant's fontanelle, wherein the method includes: detecting intracranial blood flow velocity within the superior sagittal sinus from a signal from an ultrasound transducer configured to be attached to the infant's head; and transmitting the signal to a system comprising: at least one of a monitor and an alarm device; and a controller communicatively connected to at least one of the monitor and the alarm device and the ultrasound transducer, the controller being configured to receive information from the ultrasound transducer relating to the velocity of blood flow within the superior sagittal sinus below the fontanelle below the transducer's location; and predicting an increase in intracranial pressure based on changes in the velocity of blood flow measured against the vessels of the superior sagittal sinus.

[0029] One embodiment of the present invention provides an apparatus for noninvasively determining intracranial blood flow velocity within intracranial vessels of a patient, wherein the apparatus includes an array of ultrasound transducers configured to be attached to the patient's head, wherein the ultrasound transducer array is configured to cover an area on the patient's head corresponding to the intracranial vessel whose blood flow velocity will be determined. For example, in one embodiment, the transducer array is adjacent to the patient's head and separated from the patient's head by a biocompatible material. At least one of a monitor and an alarm device communicates with the ultrasound transducer array. A controller is communicatively connected to at least one of the monitors and alarm devices and the transducer array. The controller is configured to: receive from the ultrasound transducer array information relating to an emitted ultrasound beam (e.g., the frequency of the emitted ultrasound beam) and a received echo signal (e.g., the frequency of the received echo signal) from the measured intracranial blood flow; determine, in real time and continuously, the Doppler shift between the emitted ultrasound beam and the received echo signal via a suitably programmed processor; and predict changes in intraocular pressure and / or intracranial pressure based on changes in blood flow velocity measured for the intracranial vessel over time. For example, the intracranial vessel may be the superior sagittal sinus. In one embodiment, the transducer array includes a first transmitter transducer for emitting a first emitted ultrasound beam and a first receiver transducer for receiving a first echo signal. In one embodiment, the first transmitter transducer and the first receiver transducer are configured to have a tilt angle θ1. In another embodiment, the transducer array includes a second transmitter transducer for emitting a second emitted ultrasound beam and a second receiver transducer for receiving a second echo signal. For example, the second transmitter transducer and the second receiver transducer are configured to have a tilt angle θ2. For example, the transducer array is configured to cover the area on the patient's head corresponding to the fontanelle. In one embodiment, it is not necessary to determine intracranial blood flow velocity using one or more of the following: Doppler imaging, displacement of a first tissue, and comparison with displacement of a second tissue. In addition, the controller can communicate with one or more patient monitoring devices used to measure intraocular pressure, oxygen saturation, EKG, arterial blood pressure, heart rate, respiratory rate, body temperature, pCO2, peak airway pressure, peak mean airway pressure, mean airway pressure, airway resistance, tidal volume, minute ventilation, intraocular pressure, systemic blood pressure, intrathoracic pressure, SpO2, and ventilator parameters.

[0030] Another embodiment of the invention provides a method for noninvasively monitoring intraocular pressure using an ultrasound transducer array configured to measure intracranial blood flow velocity within intracranial vessels of a monitored patient. The method includes providing an emitted ultrasound beam from a transmitter transducer of the transducer array to the intracranial vessels. An echo signal from the intracranial vessels is detected at a receiver transducer of the transducer array, wherein the transmitter and receiver transducers are housed within a housing located on the patient's head and covering an area of ​​the intracranial vessels from which the blood flow velocity will be measured. The frequency of the emitted ultrasound beam and the frequency of the echo signal are received by a system including at least one of a monitor and / or an alarm device. A controller is communicatively connected to at least one of the monitor and alarm devices, as well as the transmitter and receiver transducers. The controller is configured to receive information related to the emitted ultrasound beam from the transmitter transducer and information related to the received echo signal from the receiver transducer, and to determine a Doppler frequency shift when the emitted ultrasound beam and the echo signal are different. Based on intracranial blood flow velocity measured within intracranial vessels (e.g., the superior sagittal sinus), changes in Doppler shift are a predictor of changes in intracranial pressure or intraocular pressure. For example, a transducer array is configured to cover an area on the patient's head corresponding to the fontanelle. In one embodiment, the transducer array does not directly contact the patient's skin. In one embodiment, the controller communicates with one or more patient monitoring devices for measuring patient oxygen saturation, electrocardiogram, arterial blood pressure, umbilical artery blood pressure, venous blood pressure, heart rate, respiratory rate, body temperature, pCO2, peak airway pressure, peak mean airway pressure, mean airway pressure, airway resistance, tidal volume, and minute ventilation.

[0031] Another embodiment of the invention provides a computer system for continuously monitoring ventilation / perfusion mismatch in a patient supported by artificial ventilation using signals from an array of ultrasound transducers configured to be noninvasively externally attached to the patient's head to monitor intracranial blood flow within intracranial vessels. The system includes a database for storing signals transmitted and received from the ultrasound transducer array, which is configured to cover an area on the patient's head corresponding to the intracranial vessel from which blood flow will be measured. A suitably programmed processor is configured to: receive signals from the ultrasound transducer array into the computer system to determine a Doppler shift, thereby calculating blood flow velocity; aggregate signals from one or more patient monitoring devices simultaneously measured with intracranial blood flow velocity; identify ventilation / perfusion mismatch; and calculate optimized settings for physiological support devices to support the patient, thereby reducing ventilation / perfusion mismatch. For example, the intracranial vessel from which blood flow is measured is the superior sagittal sinus, and, for example, the transducer array is configured to cover an area on the patient's head corresponding to the fontanelle. In one embodiment, the transducer array includes a transmitter transducer for emitting an ultrasound beam and a receiver transducer for receiving echo signals. In another embodiment, the controller communicates with one or more patient monitoring devices for measuring patient oxygen saturation, electrocardiogram, arterial blood pressure, heart rate, respiratory rate, body temperature, pCO2, peak airway pressure, peak mean airway pressure, mean airway pressure, airway resistance, tidal volume, and minute ventilation.

[0032] The further scope of the invention will be set forth in part in the following detailed description, and will in part become apparent to those skilled in the art upon reading the following, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and obtained by the means and combinations specifically pointed out in the appended claims. Attached Figure Description

[0033] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate one or more embodiments of the invention and, together with the specification, serve to explain the principles of the invention. The drawings are for illustrative purposes only and should not be construed as limiting the invention. In the drawings:

[0034] Figure 1 The emitted Doppler ultrasound beam is shown as a reflection of scattered particles flowing from a blood vessel.

[0035] Figure 2 An embodiment of the sensor configuration of the present invention is shown.

[0036] Figure 3 An embodiment of the sensor configuration of the present invention is shown.

[0037] Figure 4An embodiment of the sensor configuration of the present invention is shown.

[0038] Figure 5 The top of a sensor configuration according to an embodiment of the present invention is shown.

[0039] Figure 6 The bottom of a sensor configuration according to an embodiment of the present invention is shown.

[0040] Figures 7A to 7B A top view and a side view of the male portion of the sensor array of a top sensor assembly according to an embodiment of the present invention are shown.

[0041] Figures 8A to 8B A side cross-sectional view and side dimension view of the bottom of a sensor assembly according to an embodiment of the present invention are shown.

[0042] Figure 9 A flowchart of a method for using a sensor according to an embodiment of the present invention is shown.

[0043] Figures 10A to 10C The test environment used to verify the determination of blood flow velocity within blood vessels by an ultrasound sensor is shown. Figure 10A The test environment uses the pump disclosed in this paper. Figure 10C ) and sensor configuration, thereby based on the flowchart ( Figure 10B (This is used to calculate the velocity of the fluid.)

[0044] Figure 11 A flowchart illustrating communication between a transducer, a controller, and a computer program according to an embodiment of the present invention is shown.

[0045] Figure 12 A piezoelectric sensor and specifications suitable for one embodiment of the present invention are shown.

[0046] Figure 13 A flowchart of a system according to an embodiment of the present invention is shown.

[0047] Figure 14 A computer program product according to an exemplary embodiment of the present invention is shown. Detailed Implementation

[0048] Ultrasound / beamforming is used for non-invasive sensing. Moving an object changes the frequency of the sound waves before and after it. This frequency shift is the Doppler effect. Now refer to... Figure 1 Ultrasonic measurement of blood flow velocity is based on the Doppler effect. A piezoelectric transducer 101 transmits ultrasound waves 105 at frequency f0 into the skin. When the echo signal 106 originates from a moving scatterer (e.g., a red blood cell 108), the received frequency f0 is... RIt deviates to a certain frequency from the transmission frequency, i.e., the Doppler frequency shift f. D :

[0049]

[0050] Where c is the speed of sound, V is the flow velocity, and θ is called the Doppler angle, which is the angle between the axis of the ultrasound beam and the direction of blood flow toward the transducer. When the scatterer moves relative to the probe (θ is not equal to 90°), the received echo will exhibit a certain frequency shift. If the scatterer moves toward the probe (0 ≤ θ < 90°), the echo frequency will be higher than the transmission frequency, which is called "forward"; if the scatterer moves away from the probe (90° < θ ≤ 180°), the echo frequency will be lower than the transmission frequency, which is called "reverse".

[0051] To ensure the value of the angle (i.e., Doppler angle) of the ultrasound beam relative to the blood vessel, according to one embodiment of the invention, a dual-beam ultrasound Doppler (DBUD) method is incorporated (Wang F et al., “Flexible Doppler ultrasound device for the monitoring of blood flow velocity”, Science Advances, 2021) (see [link to documentation]). Figure 2 (Now for reference) Figure 2 According to one embodiment of the invention, a device is configured to noninvasively determine the velocity of intracranial blood flow. The device comprises a 2x2 sensor array of transmitter / receiver pairs (a first transducer transmitter and transducer receiver pair with tilt angle θ1 and a second transducer transmitter and transducer receiver pair with tilt angle θ2) having two different transducer tilt angles θ1 and θ2. Methods for determining the velocity of intracranial blood flow using transmitters / receivers can utilize one or more of, for example, Snell's law and the Doppler shift equation:

[0052]

[0053] The frequency shift f between the transmitted wave (f) and the received wave D Used to calculate blood flow velocity (v), c = speed of sound in soft tissue = approximately 1540 m / s. =Beam Angle. The angle at which the emitted beam is emitted will be refracted into a new angle at the interface between the sensor housing and the skin. According to Snell's Law, the incident beam angle θ can be related to the refraction angle γ, where c1 is the speed of sound in the first medium (sensor housing) and c2 is the speed of sound in the second medium:

[0054] Snell's Law:

[0055]

[0056] System of equations:

[0057]

[0058] Solve for absolute blood flow velocity =

[0059]

[0060] Where c is the speed of sound in blood, f0 is the transmission frequency, f1 and f2 are the Doppler frequency shifts generated by the two ultrasound beams, and γ1 and γ2 are the Doppler angles. θ1 and θ2 are the transducer tilt angles. η is the refractive index, which is equal to the ratio of the speed of sound in the shell material to the speed of sound in soft tissue.

[0061] We define:

[0062]

[0063] Right now,

[0064]

[0065] Then, we combine formula (5) with formula (1):

[0066]

[0067] According to formula (6), we obtain

[0068]

[0069] Then, we calculate the sum of the squares of the two equations above:

[0070]

[0071] Now we divide the two equations in (7):

[0072]

[0073] According to formula (8), the absolute velocity is obtained.

[0074]

[0075] Substituting equation (9) into (5), we obtain the Doppler angles γ1 and γ2.

[0076]

[0077] in,

[0078]

[0079] The piezoelectric crystal in the transducer of an ultrasonic transmitter vibrates at the same frequency (f) as the applied AC voltage, thereby generating ultrasonic waves.

[0080]

[0081] Wherein, f is the frequency shift between the transmitted frequency (f) and the received wave (also referred to as the echo signal in this paper). D Used to calculate blood flow velocity (v), where c = speed of sound in soft tissue = 1540 m / s, and Θ1 is the angle of refraction of the emitted beam relative to a vertical line forming a 90-degree angle with respect to the skin below the transducer location, and θ1 is the transducer tilt angle / beam angle relative to a vertical line forming a 90-degree angle with respect to the skin below the transducer location, such as... Figure 2 As shown. For example, in one embodiment, a sensor with the following design specifications is used:

[0082] - A transmission frequency of approximately 2MHz;

[0083] - The base of the housing is approximately 20mm in diameter;

[0084] - Transducer tilt angles of approximately 8° and approximately 10°;

[0085] - Continuous wave (transmitter and receiver operating simultaneously).

[0086] Now for reference Figure 2 This illustrates an ultrasound sensor design according to an embodiment of the present invention. Redundancy of the signal used for mathematical calculation of the Doppler angle is shown, and in one aspect, vascular angle calculation is not required, and absolute blood flow velocity can be calculated (without calibration) based on the transmitted beams 205 and 206 and the detected echo signals 217 and 221.

[0087] Another embodiment provides signal processing, for example, between contralateral or front-to-back sensors on a head (not shown), using transmitted beams and echo signals, and informing the sensors of the arrangement and / or design. Signals of interest may include:

[0088] 1. Fluid flow – the velocity measured within the blood vessel;

[0089] 2. Acoustic Waves – An ultrasound beam reflected as an echo signal from the fluid (scattering particles within the fluid, i.e., red blood cells) within the measured blood vessel is deflected relative to the transmitted beam. Given the output of HFV parameters (whether or not intraocular pressure is measured), real-time detection of V / Q and any perfusion mismatch, and providing therapeutic intervention / adjustment to the HFV delivered to the patient, would be beneficial.

[0090] Now for reference Figure 2Transmitter transducers 201 and 203 generate incident beams (also referred to herein as ultrasound / beams) 213 and 215, respectively, wherein transmitter transducers 201 and 203 have transducer tilt angles θ1 and θ2, respectively. In one embodiment of the invention, the transducers are housed within a housing 220 and do not directly contact the patient. In another embodiment, the transducers are in direct contact with the patient's head, or cover the patient's head without a housing, or the sensor is close to the patient's head but not in direct contact. At the interface between the housing 220 and the surface of the skin / soft tissue 200, the incident beams 213 and 215 will be refracted to generate beams 213 and 215, respectively, with angles θ1 and θ2. and Transmitted beams 205 and 206 enter blood vessel 207 at Doppler angles γ1 and γ2, respectively. The transmitted beams have a frequency (f) as fluid (e.g., blood) flows in the direction indicated by arrow 210. This frequency is shifted when the transmitted beams encounter a scatterer 208 in blood vessel 207. The shifted signals are reflected back to the transducer array as echo signals 217 and 221 and detected by receiver transducers 202 and 204, respectively. The echo signals 217 and 221 are recorded by the system and compared with the frequency of the transmitted beams to determine the velocity of the scatterer fluid in the blood vessel. According to Snell's law, when... =8° and When the angle is 10° and it is a PDMS sensor housing, the angle of refraction is... and The angles will be approximately 11.5° and 14.4° respectively.

[0091] Table 1 provides the expected sound velocity estimates in different media.

[0092] Table 1

[0093]

[0094] Now for reference Figure 3 In one embodiment of the invention, each transducer is, for example, but not limited to, a disc-shaped piezoelectric transducer, which acts as, for example, a capacitor of about 0.036 nF. For example, in a 2x2 sensor array, two transducers act as transmitters and two transducers act as receivers. In one embodiment, a microcontroller (e.g., an Arduino Uno R3 programmable microcontroller) and fast (pulse width modulation) PWM are used to send a 2 MHz signal from pin 11. A PN2222 transistor is used to drive both transmitters from pin 11 to buffer the signal.

[0095] Now for reference Figure 4In one embodiment, each receiver transducer is connected to an amplifier circuit with a bandpass filter ranging from approximately 150 Hz to 2 MHz, where echo frequencies below approximately 150 Hz are associated with tissue and blood vessel surfaces and are therefore eliminated. These specifications are achieved using the following equation, where f1 represents the high cutoff frequency and f2 represents the low cutoff frequency:

[0096]

[0097] By selecting the feedback resistor R F and input resistance R I The value is used to set the magnification factor, for example:

[0098]

[0099] Prototyping using Arduino allows for the simultaneous transmission of 2MHz signals to two transducers. Recording from the receiver transducer can be performed using an oscilloscope or a programmable microcontroller, such as a digital signal controller like the dsPIC33 series, for example, transmitting and recording from the same device.

[0100] Figures 10A to 10C The test system includes polydimethylsiloxane (PDMS) and has channels for simulating blood fluid. Given that PDMS is widely used to simulate human tissue, the test system is used to test the sensitivity of sensor configurations. For example, based on a series of values ​​for the superior sagittal sinus of an infant, the channel diameter can be configured with the following parameters: channel diameter: 1.6 mm, 2.8 mm, 6.4 mm; channel depth: 3 mm, 5 mm, 10 mm; fluid flow rate: 170 mL / min, 300 mL / min, 450 mL / min (AJNR Am J Neuroradiol. Sep 2000; 21(8): 1497-501).

[0101] When the actual speed is set according to the pump flow rate, the accuracy is determined by monitoring the difference between the measured speed and the actual speed. (Vertical peristaltic pump 1002 with adjustable flow rate) Figure 10C ) for use with rubber tubing 1001 of length "L" and diameter "D" Figure 10A The fluid is pumped through the PDMS channel. A blood-simulated fluid (BMF) with similar viscosity and acoustic properties to human blood is used (e.g., Kamoer Fluid Technologies Ltd. (DIP-3-B25)).

[0102] According to one embodiment of the invention, the sensor housing material is made of polydimethylsiloxane (PDMS) or medical-grade silicone (e.g., a 3D printed mold). The component includes, for example... Figure 5The tops of the convex transducer portions 501, 502, 503, and 504 are shown, with wiring ports (not shown) passing through each convex transducer portion. According to one embodiment of the invention, Figure 5 The upper part shown is located in Figure 6 As shown at the bottom. Figure 6 The bottom shown provides openings 601, 602, 603, and 604 for assembling the convex transducer portion. For example, Figure 5 The top component shown has a sliding insertion into Figure 6 The convex transducer portions 501, 502, 503, and 504 are located in the openings of the channels at the bottom. (Reference) Figure 5 As shown at the top, wiring is attached (e.g., soldered) to the transducer and fed in through ports in 501, 502, 503, and 504, and the transducer is located at... Figure 6 The bottom of the housing is shown with openings in channels 601, 602, 603, and 604. The bottom and top of the housing are assembled together, for example, by pressure fitting. The bottom of the housing includes a base 607. The base is attached to the head of a patient, for example, an infant, above the fontanelle. The base 607 can be attached to the head via adhesive on its edge to ensure that the probe is positioned above the intracranial vessel of interest.

[0103] Now for reference Figure 7A Sensor components Figure 5 The top view shown illustrates the diameter (in mm) of each convex component. Now refer to... Figure 7B , Figure 7B It is a side view of the top of the convex parts 501 and 502 and the base 505, which have the dimensions shown in the figure (all in millimeters).

[0104] Now for reference Figure 8A , showed Figure 6 The cross-section shown is of the bottom of a sensor assembly according to an embodiment of the present invention, the bottom having openings 601 and 602 and the dimensions of the depth and tilt angle of each channel being matched with the tilt angle of the transducer transmitter / receiver. Figure 8B An embodiment of the present invention is shown. Figure 6 The image shows a side view of the sensor assembly with its dimensions at the bottom.

[0105] Now for reference Figure 9The signal processing flowchart begins at 901, where the fluid flow rate in the blood vessel is calculated based on the raw signal 903 emitted from the transmitter transducer. The frequency 903 detected at the receiver transducer is compared with the emitted frequency and recorded by the system, and the velocity of the fluid within the blood vessel is calculated 902. The calculated velocity is sent in real-time to a graphic display 905 and recorded in a data logger 904, and if it is determined that the calculated velocity is too high or too low compared to standard care values, these values ​​are used for treatment adjustments (e.g., HFV) and as a proxy indicator of intracranial pressure. The software used to execute the algorithm should be integrated with a programmable microcontroller compatible with Windows, MacOS, and Linux. The sensor may include an array of ultrasonic transducers housed in a medical-grade silicone container, shaped to be, for example, adhered to an infant's head using medical-grade adhesive to cover the fontanelle, where the average fontanelle size of an infant is approximately 1 to 3 cm.

[0106] Now for reference Figures 10A to 10C An embodiment of an ultrasonic sensor testing system is shown therein. Figure 10A The diagram illustrates a simulated blood vessel 1001 with length "L" and diameter "D". An ultrasound sensor emits a beam 1001 into simulated neonatal tissue / embedded tube. Fluid is pumped into the blood vessel in the closed-loop system via a peristaltic pump 1002. Fluid flow rate is measured to obtain the velocity within the system 1005.

[0107] Now for reference Figure 11 In another embodiment, the ultrasonic sensor includes a transmitter-receiver pair 1101. The ultrasonic sensor communicates with an electrical module 1102. The electrical module communicates with a computer to determine when to start and stop transmitting signals 1103. The controller is programmed using a microcontroller-compatible coding environment to record Doppler signals and calculate speeds.

[0108] Now for reference Figure 12 A specification sheet for a piezoelectric disk transducer according to an embodiment of the present invention is provided.

[0109] In one embodiment of the invention, the HFV settings are notified and / or adjusted in response to real-time monitoring of the hemodynamic status of intracranial blood flow at the superior sagittal sinus of the infant; using the sensors described herein. Additional patient system values ​​selected from one or more of the following—intraocular pressure, heart rate, systemic blood pressure, intrathoracic pressure, SpO2, and ventilator parameters—are also monitored to provide a aggregated output of the patient's status. For example, in addition to the blood flow velocities measured herein, one or more system parameters are transmitted to the controller.

[0110] In at least one embodiment, and as will be readily understood by those skilled in the art, the apparatus according to the invention will include a general-purpose or special-purpose computer programmed with computer software that implements the steps described above. This computer software may employ any suitable computer language, including C++, FORTRAN, BASIC, Java, assembly language, microcode, distributed programming languages, etc. The apparatus may also include multiple such computer / distributed systems implemented in various hardware (e.g., connected via the Internet and / or one or more intranets). For example, data processing may be performed by a suitably programmed microprocessor, cloud computing, application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), etc., combined with appropriate memory, network, and bus elements.

[0111] Now for reference Figure 13The flowchart illustrates an example healthcare system 1500 for patient monitoring, assessment, and / or diagnosis and / or intervention feedback according to an embodiment of the present invention. The example system 1500 includes an ultrasound sensor device 1510 to be placed on a patient's head, an information subsystem 1520, an acquisition engine 1530, a reconstruction engine 1540, and a diagnostic engine 1550 for interaction with a person 1502 (e.g., a physician, nurse, technician, and / or other healthcare practitioner) and a patient 1506. Components of the healthcare system 1500 may be implemented using one or more processors combined with memory, etc., executing hard-coded configurations, firmware configurations, software instructions, etc. For example, one or more components of system 1500 may include a processor-based system comprising combinations of hardware and / or software code, routines, modules, or instructions adapted to perform the functions discussed herein, including various elements performing the methods described elsewhere. It should be noted that such software routines can be embodied in manufacturing (e.g., compact disks, hard disks, flash memory, USB-based drives, random access memory (RAM), read-only memory (ROM), etc.) and configured to be executed by a processor to implement the functions described herein. Using the example system 1500, the patient 1504 can be continuously examined via ultrasound sensors 1510 (e.g., one or more embodiments of ultrasound transducers as shown herein) and the information can be forwarded to the information subsystem 1520 and / or the acquisition engine 1530. The information subsystem can also receive data from other patient monitoring devices and other monitoring equipment, such as O2 saturation, heart rate, pulse, blood pressure, intraocular pressure, ventilator settings, and patient respiratory parameters. Ventilation settings can be specified and / or influenced by deployed deep learning network models / devices (e.g., CNNs, RNNs, etc.). Based on information obtained from one or more ultrasound sensors, it can be used alone or in conjunction with the information subsystem 1520 (e.g., with the opportunity to add information about the patient, such as weight, gestational age, blood volume, and medications). Information from the information subsystem 1520 and / or the acquisition engine 1530, as well as feedback from the imaging device 1510, can be collected and fed to a deep learning network model under training to modify future settings, recommendations, etc., for example, for patient management. The deep learning network model under training can periodically and / or process feedback when specific criteria are met, and generate an updated model for deployment relative to system 1500. Additionally, the (local or remote) memory 1560 can contain a set of expected or target values ​​for physiological signals of interest. The storage module can be updated from time to time with target or expected values ​​based on the latest research, for example, on best practices regarding target values ​​of one or more physiological parameters as indicators for managing patient treatment interventions and therapies.

[0112] Now for reference Figure 14The diagram illustrates a computer program product 1600 according to an exemplary embodiment. In one embodiment, the example computer program product 1600 is provided using a signal carrying medium 1602. The signal carrying medium 1602 may include one or more programming instructions 1604, which, when executed by one or more processors, can provide the above-mentioned... Figures 1 to 13 The described function or part of a function. In some examples, the signal carrying medium 1602 may be a computer-readable medium 1606, such as, but not limited to, a hard disk drive, a compact disc (CD), a digital video optical disc (DVD), digital magnetic tape, a memory, etc. In some embodiments, the signal carrying medium 1602 may be a computer-recordable medium 1608, such as, but not limited to, a memory, a read / write (R / W) CD, a R / W DVD, etc. In some embodiments, the signal carrying medium 1602 may be a communication medium 1610, such as, but not limited to, digital and / or analog communication media (e.g., fiber optic cables, waveguides, wired communication links, wireless communication links, etc.). For example, the signal carrying medium 1602 can be transmitted wirelessly via the communication medium 1610.

[0113] The systems and methods according to one embodiment of the present invention can also be adapted to monitor and / or diagnose and / or resolve other diseases, such as space-occupying lesions (e.g., tumors), hemorrhagic lesions, traumatic brain injury, etc., but are not limited thereto. One aspect of the embodiments of the present invention provides for monitoring and / or diagnosing and / or resolving any lesions in the skull or brain that impair blood flow, since any space-occupying lesion in the skull will affect blood flow in the rich blood vessels. For example, a tumor, during its growth, compresses blood vessels in the brain and alters blood flow. Changes in the blood flow velocity in the blood vessels will reflect the rate of tumor growth, or more importantly, the regression of the tumor during treatment or after surgery.

[0114] One embodiment of the present invention provides a system and method for non-invasive (with or without Doppler imaging), continuous or intermittent, and real-time monitoring of intracranial pressure in a patient, enabling continuous or intermittent monitoring of intracranial pressure and its changes, and comparison with physiological intracranial blood flow velocity measurements of care standards for patients with similar body size, age, and / or blood volume. Blood flow velocity values ​​serve as an early indicator of ventilation / perfusion mismatch and / or as a surrogate indicator of IOP. Blood flow velocity values ​​are also used to provide feedback to patient support and monitoring devices to adjust patient treatment protocols to reduce the risk of intracranial pressure exceeding safe values ​​or care standards, thereby managing the risk of ROP or intracranial hemorrhage.

[0115] For patients receiving HFV therapy, it is beneficial to monitor blood flow within intracranial vessels (e.g., the superior sagittal sinus below the fontanelle) in real-time and continuously. An external sensor located on the head of the ventilated patient sends an emitted ultrasound beam to the vessel and records the received signal (echo signal). The blood flow velocity within the vessel below the sensor is calculated based on the emitted ultrasound beam from the transmitter transducer and the echo signal received by the receiver transducer. The calculated blood flow velocity, measured from the echo signal received from the emitted beam sent by the external sensor system, is an indication of intracranial pressure and is used to determine the risk of actual ventilation / perfusion mismatch and to inform interventions for ventilator settings or other treatment interventions to reduce the risk of, for example, intracranial hemorrhage and / or ROP by actively managing / changing the HFV therapy settings delivered to the patient and / or adjusting the HFV settings to achieve ventilation / perfusion matching when the blood flow velocity measured by the transducer exceeds the upper or lower limits associated with acceptable intracranial pressure, considering ventilator settings or within standards of care.

[0116] In another embodiment, V / Q matching is optimized to mitigate adverse consequences. For example, when machine learning is utilized, relevant signals from multiple or all patient monitoring devices can be automatically and in real-time integrated / aggregated, and adjustments can be initiated to optimize V / Q matching, thereby mitigating adverse consequences such as pneumothorax, intraventricular hemorrhage, and ROP. Similarly, the titration of vasoactive drugs, nitric oxide, and ventilator settings can be facilitated, thereby improving clinical outcomes. Therefore, sensors become an indispensable and crucial component of the critical care environment.

[0117] By replacing the reactants and / or operating conditions generally or specifically described in this invention with the reactants and / or operating conditions used in the foregoing examples, the foregoing examples can be repeated and similar successes can be obtained.

[0118] Note that in the specification and claims, "about" or "approximately" means within twenty percent (20%) of the stated value. All computer software disclosed herein can be embodied on any computer-readable medium (including combinations of media), including but not limited to CD-ROM, DVD-ROM, hard disk drive (local or network storage device), USB key, other removable drives, ROM, and firmware.

[0119] Although the invention has been described in detail with reference to these embodiments, other embodiments can achieve the same effects. Various variations and modifications of the invention will be apparent to those skilled in the art, and all such modifications and equivalents are intended to be covered in the appended claims. For example, the system can also be used for invasive treatment of elderly patients with closed fontanelles. A hole is drilled in the skull and attached to a transducer to determine intracranial pressure. Alternatively, a suitably programmed processor can be used to automatically and in real time aggregate and / or evaluate signals from a patient monitoring device (which may be combined with the output signal of an ultrasound sensor used to noninvasively (or invasively in subjects with closed fontanelles rather than open fontanelles) monitor the cerebral hemodynamic status of a subject (e.g., a preterm infant) to optimize the setup of the support process and the medications used for delivery, thereby alleviating elevated IOP (a factor contributing to ROP). Furthermore, in one or more embodiments, the systems and methods described herein are automated and can be used to screen or monitor changes in a patient's intracranial pressure (increase or decrease) based on measured intracranial blood flow velocity. The system automatically alerts the user to changes in intracranial pressure and / or blood flow velocity, providing suggested modifications based on nursing parameter standards stored in a lookup table in the system's memory. This allows for adjustments to patient supportive care based on intracranial pressure and / or intracranial blood flow velocity values, which the user then adjusts accordingly. All references, applications, patents, and publications cited above are incorporated herein by reference in their entirety.

Claims

1. An apparatus for non-invasively determining intracranial blood flow velocity within an intracranial blood vessel of a patient, wherein, The device includes: An ultrasound transducer array is configured to be attached to a patient’s head, wherein the transducer array is configured to cover an area on the patient’s head corresponding to an intracranial vessel for which blood flow velocity will be determined. At least one of the monitors and alarm devices communicates with the ultrasonic transducer array; A controller, communicatively connected to at least one of the monitor and the alarm device and the transducer array, is configured to receive information from the ultrasound transducer array relating to the emitted ultrasound beam and the received echo signal from the measured intracranial blood flow. The Doppler frequency shift between the transmitted ultrasonic beam and the received echo signal is determined in real time and continuously by a properly programmed processor; and Based on the changes in blood flow velocity over time measured for the intracranial vessels, changes in intraocular pressure or intracranial pressure are predicted.

2. The apparatus of claim 1, wherein, The intracranial vessel in question is the superior sagittal sinus.

3. The apparatus of claim 1, wherein, The transducer array includes a first transmitter transducer for transmitting a first transmitted ultrasonic beam and a first receiver transducer for receiving a first echo signal.

4. The apparatus of claim 1, wherein, The controller communicates with one or more patient monitoring devices for measuring intraocular pressure, oxygen saturation, EKG, arterial blood pressure, umbilical artery blood pressure, venous blood pressure, heart rate, respiratory rate, body temperature, pCO2, peak airway pressure, peak mean airway pressure, mean airway pressure, airway resistance, tidal volume, minute ventilation, intraocular pressure, systemic blood pressure, intrathoracic pressure, SpO2, and ventilator parameters.

5. The apparatus of claim 1, wherein, The transducer array is configured to cover the area on the patient's head corresponding to the fontanelle.

6. The apparatus of claim 3, wherein, The first transmitter transducer and the first receiver transducer are configured to have a tilt angle θ1.

7. The apparatus of claim 1, wherein, The transducer array includes a second transmitter transducer for transmitting a second transmitted ultrasonic beam and a second receiver transducer for receiving a second echo signal.

8. The apparatus of claim 7, wherein, The second transmitter transducer and the second receiver transducer are configured to have a tilt angle θ2.

9. The apparatus of claim 1, wherein, The intracranial blood flow velocity was determined without Doppler imaging.

10. A method of non-invasively monitoring intraocular pressure using a transducer array configured to measure intracranial blood flow velocity within intracranial blood vessels of a monitored patient, wherein, The method includes the following steps: Provide the intracranial blood vessels with transmitted ultrasonic beams from the transmitter transducers of the transducer array; Echo signals from the intracranial blood vessels are detected at the receiver transducer of the transducer array, wherein the transmitter transducer and the receiver transducer are located on the patient's head and within a housing covering the area of ​​the intracranial blood vessels from which the blood flow velocity will be measured. The system transmits the emitted ultrasonic beam and the received echo signal to a system comprising: At least one of the monitoring and alarm devices; and A controller, communicatively connected to at least one of the detection and monitoring devices, the alarm device, the transmitter transducer, and the receiver transducer, is configured to: receive information from the transmitter transducer relating to the transmitted ultrasonic beam and information from the receiver transducer relating to the received echo signal, and determine a Doppler frequency shift when the transmitted ultrasonic beam and the echo signal are different; and The changes in intracranial pressure or intraocular pressure are automatically predicted based on the changes in Doppler frequency shift as an indication of intracranial blood flow velocity measured in the intracranial vessels.

11. The method of claim 10, wherein, The intracranial vessel in question is the superior sagittal sinus.

12. The method of claim 10, wherein, The transducer array includes a transmitter transducer for emitting ultrasonic beams and a receiver transducer for receiving echo signals.

13. The method of claim 10, wherein, The controller communicates with one or more patient monitoring devices for measuring patient oxygen saturation, electrocardiogram, arterial blood pressure, umbilical artery blood pressure, venous blood pressure, heart rate, respiratory rate, body temperature, pCO2, peak airway pressure, peak mean airway pressure, mean airway pressure, airway resistance, tidal volume, and minute ventilation.

14. The method of claim 10, wherein, The transducer array is configured to cover the area on the patient's head corresponding to the fontanelle.

15. The method of claim 10, wherein, The transducer array does not come into direct contact with the patient's skin.

16. A computer system for continuously monitoring intracranial blood flow velocity in a patient supported by artificial ventilation using signals from an ultrasound transducer array configured to be externally attached to the patient's head to monitor blood flow within intracranial blood vessels, wherein, The system includes: A database for storing signals transmitted and received from the ultrasound transducer array, which is configured to cover the area on the patient's head corresponding to the intracranial vessels to be measured. Properly programmed processors with instructions are used for: The signal from the ultrasonic transducer array is received into the computer system; The intracranial blood flow velocity is calculated based on the Doppler shift of the signal from the ultrasonic transducer array; The intracranial blood flow velocity is aggregated with signals from one or more patient monitoring devices that are simultaneously measured with the intracranial blood flow velocity. Identifying ventilation / perfusion mismatch; and Calculate the optimal settings of patient monitoring devices that support the patient to reduce ventilation / perfusion mismatch.

17. The computer system according to claim 16, wherein, The intracranial vessel in question is the superior sagittal sinus.

18. The computer system according to claim 16, wherein, The transducer array includes a transmitter transducer for emitting ultrasonic beams and a receiver transducer for receiving echo signals.

19. The computer system according to claim 16, wherein, The signals from the one or more patient monitoring devices are selected from patient oxygen saturation, electrocardiogram, arterial blood pressure, heart rate, respiratory rate, body temperature, pCO2, peak airway pressure, peak mean airway pressure, mean airway pressure, airway resistance, tidal volume, minute ventilation, or any combination thereof.

20. The computer system according to claim 16, wherein, The transducer array is configured to cover the area on the patient's head corresponding to the fontanelle.

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