Systems and methods for conducting non-visual diagnostics using artificial intelligence with multiple aperture ultrasound imaging

Abstract

A diagnostic ultrasound imaging method is provided, that can include transmitting an omni-directional unfocused ultrasound waveform into a target region with a transmit aperture of a multiple aperture ultrasound imaging probe; receiving ultrasound echoes from the target region with a plurality of receive apertures of the multiple aperture ultrasound imaging probe; with a processor of the multiple aperture ultrasound imaging probe, extracting echo data from the received ultrasound echoes that includes diameters of the peripheral artery and the intracranial artery at systole and diastole, and flow through the peripheral and intracranial artery, and with the processor, calculating an intracranial pressure (ICP) with the echo data.

Description

SYSTEMS AND METHODS FOR CONDUCTING NON- VISUAL DIAGNOSTICS USING ARTIFICIAL INTELLIGENCE WITH MULTIPLE APERTURE ULTRASOUND IMAGINGPRIORITY CLAIM

[0001] This patent application claims priority to U.S. provisional patent application no. 63 / 727,063, titled “NON-INVASIVE INTRACRANIAL PRESSURE MEASUREMENT WITH ULTRASOUND,” filed on December 2, 2024, and U.S. provisional patent application no. 63 / 757,716, titled “SYSTEMS AND METHODS FOR CONDUCTING NON- VISUAL DIAGNOSTICS USING ARTIFICIAL INTELLIGENCE WITH MULTIPLE APERTURE ULTRASOUND IMAGING,” and filed on February 12, 2025, which are both herein incorporated by reference in their entirety.INCORPORATION BY REFERENCE

[0002] Unless otherwise specified herein, all patents, publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.FIELD

[0003] This invention generally relates to medical diagnostics and specifically to diagnostic data collected through the use of ultrasound.BACKGROUND

[0004] Medical imaging today uses multiple modalities and often requires significant expertise of both the technician and or the physician to capture image data and then to conduct a diagnosis. That same level of expertise is required to conduct interventional procedures requiring the placement of instruments and therapies under image guidance.

[0005] Separate but related to diagnostic ultrasound imaging, is the fact that understanding a physiological condition or establishing a diagnosis can sometimes be concluded through quantitative analysis of the tissue being examined without visualization of that tissue. Providing qualitative and quantitative assessment of the patient’s condition has become accepted for everything determining bladder volume for catheterization to determining gastric volume prior to aestheticizing high risk patients. Perhaps most well- known is the non-imaging evaluation of bone density using ultrasound or x-ray. In these- 1 -SG Docket No. 10622-731.600types of cases, a diagnostic data point is acceptable as a result of a medical ultrasound examination even when an image is not produced. For example, ultrasound bone densitometers produce t-score and z-score predictors of osteoporosis.

[0006] Much of the reason that ultrasound imaging equipment is not used to deliver more qualitative or quantitative data is that a trained technologist must aim the equipment at the appropriate tissue to be evaluated, which usually requires imaging expertise on the part of the user. Additionally, most conventional ultrasound imaging systems cannot image beyond traditional barriers to ultrasound wave transmission such as bone or gas. These natural barriers are caused by speed-of-sound changes as well as signal attenuation due to large mismatch of the acoustic impedance between tissues and bones. For instance, when imaging the liver from behind a rib, the transmit energy is largely attenuated by the rib bone, and only the portions of the transducer which extend beyond the rib over to the intercostal space are able to acquire decipherable image.

[0007] Measuring intracranial pressure (ICP) is necessary when there is a severe head injury or brain / nervous system disease. It also may be done after surgery to remove a tumor or fix damage to a blood vessel if the surgeon is worried about brain swelling (source link). The current methods for measuring ICP all involve an invasive procedure that starts with drilling a hole in the skull. The intraventricular catheter is the most accurate monitoring method. The current methods create significant risk associated with a craniotomy and a foreign body communicating with the outside world. Noninvasive measurement of ICP is a major unmet need in the care of patients with intracranial pathology or who are suspected of having intracranial pathology. It is particularly difficult in the setting of trauma in austere environments where x-ray, CT and MRI are not available.SUMMARY

[0008] A diagnostic ultrasound imaging method is provided, comprising the steps of: positioning a multiple aperture ultrasound imaging probe near a skull of a subject; transmitting one or more omni-directional unfocused ultrasound waveforms through a peripheral artery and into a brain and an intracranial artery of the subject with a transmit aperture of a multiple aperture ultrasound imaging probe; receiving ultrasound echo data with a plurality of receive apertures of the multiple aperture ultrasound imaging probe; with a processor of the multiple aperture ultrasound imaging probe, calculating one or more diameters of a peripheral artery segment and one or more diameters of an intracranial artery segment at systole and diastole from the echo data; with the processor, calculating a flow rate through the peripheral artery segment and through the intracranial artery segment; and with - 2 -SG Docket No. 10622-731.600the processor, calculating an intracranial pressure (ICP) of the subject based at least in part on the one or more diameters of the peripheral artery segment and the one or more diameters of the intracranial artery segment at systole and diastole, and the flow rate through the peripheral artery segment and the intracranial artery segment.

[0009] In some aspects, the peripheral artery comprises a temporal artery, a middle cerebral artery, or an anterior cerebral artery.

[0010] In some aspects, the intracranial artery comprises a posterior cerebral artery.

[0011] In one aspect, a length of the intracranial artery segment or the peripheral artery segment is user-set.

[0012] In some aspects, the echo data comprises 2D or 3D echo data.

[0013] In some aspects, one or more diameters of the peripheral artery segment and the one or more diameters of the intracranial artery segment are calculated with a machine learning model.

[0014] In one aspect, the flow rates are calculated algorithmically.

[0015] In some aspects, the flow rates are measured with a doppler imaging mode of the multiple aperture ultrasound imaging probe.

[0016] An ultrasound imaging system is provided, comprising: a multiple aperture ultrasound imaging probe configured for placement near a skull of a subject, the multiple aperture ultrasound imaging probe comprising a transmit configured to transmit one or more omni-directional unfocused ultrasound waveforms through a peripheral artery and into a brain and an intracranial artery of the subject, the multiple aperture ultrasound imaging probe further comprising a plurality of receive apertures configured to receive ultrasound echo data; one or more processors configured to: calculate one or more diameters of a peripheral artery segment and one or more diameters of an intracranial artery segment at systole and diastole from the echo data; calculate a flow rate through the peripheral artery segment and through the intracranial artery segment; and calculate an intracranial pressure (ICP) of the subject based at least in part on the one or more diameters of the peripheral artery segment and the one or more diameters of the intracranial artery segment at systole and diastole, and the flow rate through the peripheral artery segment and the intracranial artery segment.

[0017] In some aspects, the peripheral artery comprises a temporal artery, a middle cerebral artery, or an anterior cerebral artery.

[0018] In some aspects, the intracranial artery comprises a posterior cerebral artery.

[0019] In one aspect, a length of the intracranial artery segment or the peripheral artery segment is user-set.

[0020] In some aspects, the echo data comprises 2D or 3D echo data.- 3 -SG Docket No. 10622-731.600

[0021] In some aspects, one or more diameters of the peripheral artery segment and the one or more diameters of the intracranial artery segment are calculated with a machine learning model.

[0022] In one aspect, the flow rates are calculated algorithmically.

[0023] In some aspects, the flow rates are measured with a doppler imaging mode of the multiple aperture ultrasound imaging probe.BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0025] FIG. l is a schematic illustration of a multiple aperture imaging probe with three transducer arrays and several points to be imaged.

[0026] FIG. 2 is a schematic diagram of an embodiment of a concave curvilinear transducer demonstrating how transmit and receive apertures can be widened around a desired view angle to achieve greater resolution of the target area.

[0027] FIG. 2A is a schematic diagram of an embodiment of a concave transducer where the transmit aperture and multiple receive apertures can be electronically controlled to operate in different positions.

[0028] FIG. 2B is a schematic diagram of an embodiment of a concave transducer where elements of the transmit and receive apertures can be utilized in rapid succession to gather more data from multiple transmit and receive apertures.

[0029] FIG. 2C is a schematic diagram of an embodiment of a concave transducer where demonstrating how transmit and receive apertures may be widened around a desired view angle to achieve greater resolution of the target area.

[0030] FIG. 2D is a schematic diagram of an embodiment of a concave curvilinear matrix with curvature in two orthogonal directions, also referred to as a Three-Dimensional (3D) array. Each element in a 3D array is displaced relative to adjacent elements in all of x, y, and z axes. In this illustration, an element or elements of a transmit aperture is designated to insonify the medium. Multiple targets in the medium are illustrated for the purpose of demonstrating how volumetric data may be gathered. Multiple receive apertures are- 4 -SG Docket No. 10622-731.600illustrated to demonstrate how simultaneous gathering of data may involve timing and tissue speed of sound variations.

[0031] FIG. 2E illustrates an embodiment of a 3D array. Multiple transmit apertures Ti through TN are indicated for the purpose of demonstrating transmit pulses being received on one or more receive apertures R2 and / or R3. A single target is indicated for the purpose of demonstrating how data may be gathered.

[0032] FIGS. 3A-3B are illustrations of the cross section of an arterial vessel and further illustrates the various forces affecting the pressure from both inside and outside the vessel.

[0033] FIG. 4A illustrates a cut-away view of anatomical schematics of various peripheral and intracranial vasculature, including, for example, the superficial temporal artery.

[0034] FIG-4B illustrates a sagittal or side view of anatomical schematics of various peripheral and intracranial vasculature, including, for example the pericallosal artery.

[0035] FIG. 4C is a coronal or plan view which illustrates anatomical schematics of various peripheral and intracranial vasculature, including, for example, the anterior and middle cerebral arteries.

[0036] FIG. 5 demonstrates a concave transducer positioned outside of the skull in relation to both the Temporal and Middle Cerebral arteries.

[0037] FIG. 6 illustrates the process for using a Computed Echo Tomography (CET) system in calculating Intracranial Pressure in a subject.

[0038] FIG. 7 demonstrates typical systolic and diastolic pressure during the cardiac cycle in an otherwise healthy patient during cardiac cycles.DETAILED DESCRIPTION

[0039] The various embodiments will be described in detail with reference to the accompanying drawings. References made to particular examples and implementations are for illustrative purposes and are not intended to limit the scope of the invention or the claims.

[0040] As described in more detail below and in Applicant’s prior patents and applications, Ping-Based Multiple Aperture (PMA) imaging involves transmission of ultrasound “pings,” echoes of which may be received by receive elements located at some distance from the transmitter. This technology is also referred to as Computed Echo Tomography (CET). Each received echo signal lies along an ellipse defined by the transmitter and receiver positions and the time interval between ping transmission and echo reception. A data element can be created virtually anywhere in a 2D grid or 3D volume.- 5 -SG Docket No. 10622-731.600Typically, ellipses crossing at a location in a 2D grid is known as a pixel. Ellipses crossing in a 3D volume are known as a voxel. An image may be formed by combining such pixels or voxels (i.e., data elements) in a way that their intersections become emphasized. Each intersection may be an image point in a two-dimensional or three-dimensional image. Concurrently and separately, groupings of data elements known as data sets may be evaluated for quantitative and / or qualitative indications of diagnostic conditions.

[0041] FIG. 1 demonstrates a ping based multiple aperture probe 100 S, with arrays 12, 14, and 16. In some embodiments, subarrays are often individual elements within each array are indicated as points a, b, c, d, e, f, g, h and i. However, sub-arrays can be located across physical gaps between arrays and should not be considered limited to individual elements on an individual array. A ping transmission is represented by the wavefront 13 (dashed wavefront(s)) generated by a transmit aperture at ‘a’ on array 12 and is indicated by wavelets. Point A in the medium or tissue 20 is meant to represent a hard structure (e.g., calcium or hardened plaque from atherosclerosis, or other hard objects such as bone), which would immediately reflect or scatter the transmitted wavefront 13 in multiple directions represented here as reflected wavefront 15 (solid wavefront(s)). The reflected wavefront emanating from point A may provide a relatively bright signal to the receive elements in arrays 12, 14, and 16. The transmitted wavefront 13 may also continue on through the medium or tissue 20 to point B, which is meant to represent an anechoic structure (e.g., a blood vessel or other soft tissue) that would provide a relatively weaker reflected wavefront 17 back to the individual transducer elements on arrays 12, 14, and 16.

[0042] Echoes from points A and B can be received by receive elements in arrays 12, 14, and 16 and used by the probe 100 to create data sets and frames used to form multiple aperture ultrasound images or for analysis by artificial intelligence engines. An electronic controller(s) or processor(s) associated with any probe on a PMA enabled system can begin the process of analyzing the data in the region of interest. A receiver element may be part of an array, or it may be an independent element used as an omni-directional receiver. It need not be used in conjunction with other elements to collect and compound data in real time. A second receiver element can be used to produce a second string of data coming off of the same ping utilized to provide receiver element data to the first receiver element. Similarly, echo data coming off of the same ping transmission can be used by a plurality of receiver elements (e.g., third, fourth, fifth, etc. receiver elements). All Data samples collected by all active receivers from the region of interest, after Analog to Digital conversion is done, are stored into data strings in Local memory. This data is referred to as RAW Data because it is- 6 -SG Docket No. 10622-731.600stored with no modifications applied to it. This data will be used by Beamformer for generating pixel or voxel data as well as by Al for diagnostics

[0043] Transducers may be contiguous in some embodiments or may be configured using multiple arrays in other embodiments. No matter the type of array, transducer elements operate independently and can be utilized to form any number of either transmit or receive apertures within the structure. As used in the embodiment in FIG. 1, the terms "transducer array" or "array" generally refers to a collection of transducer elements mounted to a common backing block. Such arrays may have one dimension (ID), two dimensions (2D), 1.5 dimensions (1.5D) or three dimensions (3D). Other dimensioned arrays as understood by those skilled in the art may also be used. Transducer arrays may also be collections of pMUT or cMUT transducer elements. An element of a transducer array may be the smallest discretely functional component of an array. For example, in the case of an array of piezoelectric transducer elements, each element may be a single piezoelectric crystal or a single machined section of a piezoelectric crystal.

[0044] In the embodiment illustrated in FIG. 2 data collected at the receiver aperture Ri is coming from a single transmit source Ti, and therefore will have a singular consistent speckle noise pattern. By itself, this is the same limiting factor of conventional ultrasound today. However, data from the transmission Ti may also be collected at aperture R2 at the same time. The channel data collected has a different aspect angle on the target, and when compounded with the aperture data at Ri will provide higher resolution and reduce speckle. In either case, energy is transmitted toward a region of interest which has at least one reflector 170. Receiver aperture Ri and aperture R2may be electronically designated to collect data for this transmit cycle by the MAUI Electronics 140. The subject of how to combine pixel data for receivers located along different physical pathways at different apertures and sometime on different arrays altogether, is the subject of US Patent 9,146,313 titled "Point Source Transmission and Speed-of-Sound Correction Using Multi-Aperture Ultrasound Imaging.”

[0045] In the embodiment illustrated in FIG. 2A the transmitter Ti is now located in a different physically separated aperture. Like FIG. 2, this sequence of transmitting from T 1 will create a unique speckle pattern for data received by transducer(s) at apertures Ri and R2. However, when the data set created at a first time in FIG. 2 is combined with the data collected at a second time in FIG. 2A, the aggregated data set will benefit from the constructive interference of the speckle noise patterns emanating from the different transmit locations. Data clarity specifically around signal frequency and amplitude benefit greatly over conventional ultrasound systems collecting data from only a single - 7 -SG Docket No. 10622-731.600transmit aperture or origin. Similarly, energy is transmitted toward a region of interest which has at least one reflector 170. Thereafter, receiver aperture Ri and aperture R2may be electronically designated to collect data for this transmit cycle by the MAUI Electronics 140.

[0046] The embodiment illustrated in FIG. 2B is an extension of the concept illustrated in FIG. 2A. In FIG. 2B, multiple receiver apertures Ri, R2 and R3 collect data from Ti at a first time. Subsequently, all receive apertures receiver apertures Ri, R2 and R3 receive additional data from the transmission at T2 at a second time, and the transmission at T3 at a third time. The natural benefit of this process is to create wider and wider apertures which improve resolution. FIG. 2B further demonstrates another unique feature of some embodiments of multiple aperture arrays called view angle control. As seen in FIG. 2B, the view angle may be defined as the angle a between lines 180 and 190 that may be drawn from Ti to 170 along line 180 and from Ri to 170 along line 190. In some embodiments, the MAUI electronics 140 may be configured to automatically move the transmit T 1 and receive Ri apertures along the array or arrays without changing the total distance between the transmit Ti and receive Ri apertures.This process of improving lateral resolution using PMA systems is described in US Patent 8,007,439 titled "Method and Apparatus to Produce Ultrasonic Images Using Multiple Apertures. The curvature of the concave probe also improves trans lateral (or resolution measured diagonally from the center of the transducer) and axial resolution (measured vertically from the center of the transducer. These improvements are in part due to the reduction in angular offset and associated “view angle” by receiving elements, and in part due to being physically closer to the image targets. Further, different transmission frequencies can be interlaced into the different transmit and receive apertures, can be utilized to further create higher resolution data sets.

[0047] FIG. 2C illustrates another important capability of some embodiments of multiple aperture arrays, referred to herein as total aperture size control. In this embodiment, the view angle created by TIA and RIA provides an obstruction- free view of the region of interest including reflector 170 which avoids obstruction 150. In this example, the system provides multiple aperture imaging with a total aperture width of Ai A. Using total aperture size control, the total aperture width can be varied either inward or outward on the array, while maintaining a fixed view angle center. Thus, in some embodiments, as a total aperture size is adjusted, both transmit and receive apertures may be electronically moved at the same rate outward or inward from the fixed view angle center so as to maintain the original view angle.- 8 -SG Docket No. 10622-731.600

[0048] Radian resolution is proportional to A / d, where 1 is wavelength and d is total aperture width. The wider the total aperture, the higher the resolution; the smaller the total aperture, the lower the resolution. The total aperture width may be varied to get the best possible resolution for a chosen view angle. For example, in the embodiment of FIG. 2C, the total aperture width may be maximized by selecting the total aperture width between TIB and RIB, resulting in a total aperture width of AIB.

[0049] US Pat. No. 9,220,478 titled “Concave Ultrasound Transducers and 3D Arrays” demonstrates many iterations of arrays configurations to produce volumetric data sets and their associated voxels. Illustration of FIG. 2D is presented here to represent a 3D array used with a PMA system to create 3D volumetric data sets. In FIG. 2D, a snapshot of multiple aperture data collection is depicted enroute to building an image of an entire volume 310. As seen in FIG. 2D, a concave 3D transducer array 300 may have a curvature about two orthogonal axes. In some embodiments, a 3D concave curved array 300 may be constructed using machined piezoelectric transducers. Calibration of a 3D array may be needed as each element of the array 300 will have slightly different positions in the x axis 301, y axis 302 and z axis 303.

[0050] As further seen in FIG. 2D, a snapshot of multiple aperture data collection is depicted en route to building an image of an entire volume 310. Here, an element or elements of a transmit aperture Ti transmit a pulse into the volume that includes scatterers such as 321 and 332. The elements making up receive aperture R2 may be assembled in a variety of shapes. Here, a square of elements makes up the receive apertures R2 and R3. As mentioned above, the speed of sound along the path from the transmit aperture Ti to the reflector 321 or 332 is irrelevant to the coherent addition of the received signals as long as a single aperture is used to receive, however, speed of sound corrections can be made to improve image quality when using multiple receive apertures R2 and R3.

[0051] In some embodiments, the size of the receive aperture R2 may be as large as for a conventional phased array (e.g., about 2cm). But unlike a conventional array, the total aperture 340 determining the lateral and transverse resolution of the system is much larger comprising the distance from the transmitter Ti to the group of receiver elements R2,and could be as wide as the entire array 300 or wider if a transmitter was located on another array within the probe (or in a separate probe in electronic communication). The elements located in the receive aperture R2 each collect volumetric data from the Ti transmit pulse.Transmitter and receiver aperture sizes and sequences may be altered throughout the entire array, similar to the sequences described FIG. 2B, but now transmitters and receivers may be located anywhere within the array and in any axis.- 9 -SG Docket No. 10622-731.600

[0052] FIG. 2E illustrates another embodiment of a 3D array 300. As seen in FIG. 2E, multiple transmit apertures Ti through TN are indicated for the purpose of demonstrating transmit pulses being received on one or more receive apertures R2 and / or R3. A single target 321 or reflector 321 is indicated for the purpose of demonstrating how data may be gathered.

[0053] Collecting data through varying tissue types naturally requires the accommodation of differing tissue acoustic impedance with differing speeds-of-sound. Pixel and voxel computations can only be accurate when these accommodations are made. US Pat. No. 9,146,313 titled "Point Source Transmission and Speed-of-Sound Correction Using MultiAperture Ultrasound Imaging" covers these methods in detail.

[0054] A processor in the PMA system, in the probe itself or in communication with the probe (e.g., wirelessly) may then be configured to conduct calculations using all data set values for all data strings. In some implementations, the data string may be collected for an entire region of interest (i.e., large sample period). In other implementations, the data may be collected for only a specific pixel and voxel (i.e. specific sample period).

[0055] The processor can then initiate the beamforming process to create digital values from Raw Data at a pixel location in the region of interest. In the case of 3D diagnostics and imaging, the same process can be utilized to create data values by voxel. The process can be repeated for multiple ping transmissions and echo data strings collected for multiple receivers.USING ULTRASOUND FOR PRESSURE MEASUREMENT / CALCULATION

[0056] In addition, increased ICP is also a risk factor for brain herniation, Brain herniation is a serious medical condition that occurs when brain tissues, cerebrospinal fluid, and blood vessels are pushed or squeezed across structures within the skull due to increased intracranial pressure. This pressure can be caused by various factors, such as traumatic brain injury, brain tumors, strokes, or intracranial hemorrhage.

[0057] There are several types of brain herniation, including:

[0058] Subfalcine (Cingulate) Herniation: The brain tissue moves under the falx cerebri, a membrane that separates the two cerebral hemispheres.

[0059] Transtentorial (Uncal) Herniation: The uncus, part of the temporal lobe, is pushed downward into the posterior fossa.

[0060] Central Herniation: Both temporal lobes are pushed downward through the tentorial notch.

[0061] Tonsillar Herniation: The cerebellar tonsils move downward through the foramen magnum, the opening at the base of the skull.- 10 -SG Docket No. 10622-731.600

[0062] Brain herniation can occur at ICPs less than those that impair CPP. Consequently, ICP monitoring and interventions that reduce ICP can be lifesaving. Finally, while accurately measuring the actual ICP is of value, being able to precisely track changes in ICP may be of equal or greater value from a clinical perspective.

[0063] Referring to FIG. 3 A, the diameter of an artery changes significantly between systole and diastole, widening during systole due to the pulse of blood and narrowing during diastole. Cerebral or intracranial arteries such as the anterior and middle cerebral arteries, the basilar artery and the peri -callosal arteries are elastic arteries without significant smooth muscle. Consequently, they do not have the ability to constrict or dilate independently. As a result, the diameter rl of cerebral arteries is determined by the pulse pressure (PP = systolic pressure - diastolic pressure), the elasticity of the arterial wall, and the intracranial (IC) pressure, with Ari defining half of the change in the intracranial artery diameter rl between systole and diastole. Extracranial arteries, such as the superficial temporal artery, are muscular arteries that contain smooth muscle in their arterial walls and, therefore, can expand or contract independently of pulse pressure in response to changes in the pathophysiologic condition of the individual. The diameter r2 of extracranial arteries also changes between systole and diastole, with Ar2 defining half of this change in diameter. The main difference between intracranial and extracranial arteries is that ICP affects the diameter of the artery. As ICP changes, Ari will change for intracranial arteries, but Ar2 will not change for extracranial arteries.

[0064] Referring to FIG. 3B, the ability to measure, estimate, or calculate ICP is critical in the setting of traumatic brain injury. The importance of knowing the ICP is that maintaining cerebral perfusion pressure (CPP) is critical for preserving blood flow and tissue perfusion in the brain. CPP is defined as the pressure difference between the pressure inside the artery ((Pi) and the pressure outside the artery (Pe). Therefore, the CPP equals the mean arterial pressure (MAP) - ICP, as shown in FIG. 3B. ICP in normal / healthy patients is typically between 7-15 mmHg, normal MAP is between 70 - 100 mmHg, and normal CPP is between 60 - 80 mmHg. Maintaining CPP > 50 mmHg is considered critical in the setting of traumatic brain injury.

[0065] For pulsatile arterial flow, as ICP increases, the difference between the vessel diameter at systole and the diameter at diastole will decrease. For laminar flow of a viscous fluid (blood) in a pipe (the assumption made for blood flow in arteries), Poiseuille’s law relates the flow rate (Q) to the pressure difference from one end of the pipe to the other (AP), the viscosity (q), the radius (r) and length (L) of the “pipe”:

[0066] Equation 1 : Q = 7tr4AP / 8qL or AP = Q(8qL) / 7tr4- 11 -SG Docket No. 10622-731.600

[0067] This means that the flow rate is directly proportional to the fourth power of the radius of the pipe (artery), meaning even small changes in diameter can significantly affect the flow rate.

[0068] Unlike intracranial vessels such as the middle and anterior cerebral arteries and the pericallosal artery, which are subject to ICP, peripheral vessels supplied by the same major artery (carotid) such as the superficial temporal artery do not have external pressures (other than atmospheric pressure) that will alter vessel diameter and flow. However, changes in the physiological condition of the individual may change vessel wall tension and diameter.

[0069] For example, the vessels listed below can have the following comparative vessel diameters:

[0070] Superficial temporal artery = 2.2 - 2.7 mm diameter

[0071] Pericallosal artery = 1.5 - 2.0 mm diameter

[0072] Anterior cerebral artery = 1.5 - 2.5 mm diameter

[0073] Middle cerebral artery = 2.6 - 2.75 mm diameter

[0074] Basilar artery = 3.0 - 3.4 mm diameter

[0075] Since the viscosity of the blood is constant and since the length of the vessels being measured can be controlled, for short vessel lengths (on the order of 1 cm or less), AP(peripheral artery)=PP and the AP(intracranial artery) = [(Psys—ICP)-(Pdia + ICP)]=[PP-(2 X ICP)] and the relationship between the representative arteries can be expressed as:

[0078] with K = a constant

[0079] which translates to

[0080] Q(intracranial artery) / Q(peripheral artery)

[0081] {pintracranial artery) X [PP-(2 X ICP)] } / pperipheral artery) X PP

[0082] where

[0083] pintracranial artery) = [pintracranial artery-systole) + pintracranial artery-diastole)] / 2

[0084] and

[0085] pperipheral artery) = [pperipheral artery-systole) + pperipheral artery-diastole)] / 2

[0086] Consequently, all of the values except for ICP can be measured using ultrasound imaging as discussed above, and standard physiologic monitoring and ICP can be calculated using the following relationship:

[0087] { [(ris+ rld) / 2]4x [PP-(2 x ICP)]} / { [(rps+ rpd) / 2]4x PP} =

[0088] Q(intracranial artery) / Q(peripheral artery)

[0089] Where:- 12 -SG Docket No. 10622-731.600

[0090] ns = radius of the intracranial artery at systole

[0091] Fd = radius of the intracranial artery at diastole

[0092] rps= radius of the peripheral artery at systole

[0093] rpa = radius of the peripheral artery at diastole

[0094] Solving for ICP as Equation 2:

[0095] Therefore, being able to measure both flow and systolic and diastolic vessel diameters of these representative vessels (or their equivalents) and comparing the dynamics of the peripheral vessel(s) to those of the intracranial vessel(s), allows for a non-invasive measure of ICP, either directly via the formulas above or using / including machine learning and / or elastography that includes cranial tissue stiffness data. Patients with an intraventricular catheter who are being monitored can be utilized to acquire the data necessary to train the machine learning algorithm(s). The MAUI system is critical to this process as it can be uniquely leveraged to acquire the required diameters, flow rates, and stiffness data.

[0096] However, as discussed, the peripheral artery (superficial temporal artery) used in this example is a muscular artery that is not simply a passive elastic vessel and can impose an independent and complicating variable in this analysis.

[0097] This conundrum can be mitigated by recognizing that in many, if not most clinical situations, the utility of knowing the exact measure of ICP is less important than following and detecting changes over time. In other words, knowing that ICP is increasing, decreasing, or remaining stable without actually knowing the measured ICP can be as valuable as knowing the specific measurements of ICP themselves. This simplifies the exercise in that only the changes in systolic and diastolic diameters and in rl (FIG. 3 A) in a consistent set of intracranial vessels need to be monitored over time.

[0098] Reductions in the two diameters with or without changes in rl would reflect an increase in intracranial pressure and the rate of change in these metrics would represent a sensitive measure of intracranial vascular and hydrodynamic stability or lack thereof. Furthermore, this would reduce the variability introduced by the need to measure a reference muscular artery (superficial temporal artery) that may introduce “noise” in the calculation of- 13 -SG Docket No. 10622-731.600ICP. In addition, the need to measure flow rates (Q) is obviated, further reducing variability, noise, and technical difficulty.

[0099] Precision in the measurement of vascular diameters in the same set of intracranial vessels then becomes the critical feature of this approach to assessing ICP changes rather than accuracy with respect to the measurement of actual level of ICP.

[0100] The mathematics above demonstrates that discerning the radii of both the peripheral and intracranial arteries at the same time is imperative for the calculation to be accurate. Identification, therefore, of ideal arteries to utilize in either data collection or imaging with an ultrasound imaging system becomes of high importance.

[0101] FIGS. 4A-4C illustrate anatomical schematics of various peripheral and intracranial vasculature, including, for example, the superficial temporal artery (FIG. 4A), the pericallosal artery (FIG. 4B), and the anterior and middle cerebral arteries (FIG. 4C).Generally, for purposes of this disclosure, the vasculature can be grouped into peripheral arteries (e.g., arteries outside the skull) and intracranial arteries (e.g., arteries inside the skull).

[0102] Referring to FIG. 5, an example of using ultrasound imaging to determine ICP is shown. In this example, the multiple aperture ultrasound imaging probe 500 is shown placed against a subject’s head, such as along the temple adjacent to the temporal artery. The probe 500 can be any probe discussed herein, including any of the probes and ultrasound imaging techniques described above in reference to FIGS. 1-2E. While the probe is positioned near the temporal artery in this example, it should be understood that the ICP calculation technique can be performed by positioning the imaging probe against other peripheral arteries. Other peripheral arteries of the head may be used for the method, including but not limited to the facial artery, the occipital artery, the posterior auricular artery, or the maxillary artery.

[0103] The probe 500 can be oriented to direct ultrasound waveforms through one or more peripheral or extracranial arteries (e.g., the temporal artery) into the skull and brain, and through one or more target intracranial arteries. In this example, the middle cerebral artery is also insonified with ultrasound energy. The probe can be used to capture ultrasound imaging data of the peripheral and intracranial arteries of choice over a given time period that includes systole and diastole of the subject. The ultrasound data can be used to obtain the diameters of the target vessels during systole and diastole, as well as the flow (Q) through the peripheral and intracranial artery of choice (e.g., using doppler flow techniques). In some embodiments, one or more processors of the ultrasound probe or system may evaluate the ultrasound imaging data and automatically calculate the diameters of the target vessels.

[0104] The example above references the middle cerebral artery as the intracranial artery of choice, but it should be understood that the ICP calculation technique can be performed by- 14 -SG Docket No. 10622-731.600insonifying other intracranial arteries. Other intracranial arteries may be used for the method, including but not limited to the anterior cerebral artery, the anterior communicating artery, the anterior choroidal artery, the lenticulostriate arteries, the posterior cerebral artery, the basilar artery, the posterior communicating artery, the posterior inferior cerebellar artery, the anterior inferior cerebellar artery, the superior cerebellar artery, or the posterior choroidal arteries.

[0105] FIG. 6 is a flowchart that illustrates the technique described above for calculating ICP in a subject with an ultrasound system. Referring to step 600, the method can include positioning an ultrasound probe near a skull of a subject.

[0106] The probe can be used to image the peripheral and intracranial arteries of choice (e.g., the temporal artery and the middle cerebral artery) at step 602. The peripheral and intracranial arteries can be imaged simultaneously (e.g., with the same ultrasound transmissions). In some examples, the imaging includes a temporal aspect, in which the diameters of the target vessels are evaluated over a preset, predetermined, or user-set time period. Therefore, the imaging data can be timestamped and stored. In some examples, a segment of the peripheral and intracranial artery is imaged. The length of each segment can be preset, predetermined, or user-set. In some examples, the length of each segment is determined by the aperture width of the imaging probe.

[0107] Imaging and / or data collection without beamforming can be accomplished at step 602 with a 2D transducer by holding the probe vertically (sagittal view) in alignment with any peripheral artery, but preferably the temporal artery. Often, the diameter of the temporal artery can be visualized even in the “long” view when aligned with the length of the artery; however, it’s also acceptable to move the probe to a “transverse” (axial view) in order to visualize the diameter of the artery. The middle cerebral artery can be imaged from either the sagittal or axial views. Ideally, both the temporal and middle cerebral arteries should be in the same 2D view.

[0108] The imaging or data collection in step 602 can also be accomplished with a 3D ultrasound imaging probe, such as the system described in FIGS. 2D-2E. When using a 3D PMA system, having both arteries in view is not problematic, and vessel measurement can be taken from within the same data set. Imaging with a ping-based 3D imaging system enables volumetric imaging to be utilized over large areas of the body. This enables easier acquisition and larger areas of visualization of difficult targets like vessels. Additionally, Al can be utilized on 3D data sets for guidance to desired anatomy (e.g. vascular structures). Further, because of a 1 to 1 ratio of channel data to pixel locations without scan conversion, 3D data can be used to identify vascular structures and association physiological characteristics without being beamformed into voxels.- 15 -SG Docket No. 10622-731.600

[0109] 3D imaging data collected by a ping-based ultrasound system, specifically using 3D or 2D arrays, to provide even higher resolution than conventional 3D imaging systems. This is in large part due to the isotropic volumetric data set being collected by the transducer from a single point of origin using predominantly and unfocused transmission. Because of this isotropic data set, there is no restriction of data in just lateral and axial resolution. This is a significant advancement when compared to conventional 3D ultrasound. Conventional ultrasound systems transmit and receive in 2D planar slices along one axis x (e.g. horizontally aligned planes), then shift transmissions to transmit and receive 2D planar slides along an orthogonal axis y (e.g. vertically aligned planes). The conventional systems then compile the 3D data set by combining the horizontal and vertical planar pixels to create voxels. That is, pixelated data in a 2D plane, then combined with adjacent or orthogonal planes to create voxels and a 3D volume. Thus, the lateral and axial resolution is actually locked in via the transmission and reception of the 2D plane being steered to. Ping-based 3D data in an isotropic volumetric data set has no such restriction. Because of the unfocused transmitter being able to be received off of any radian or vector in 360 degrees of possibly transmit vectors, receivers predominantly receive and beamform echoes that are not part of the original transmit plan. Meaning that there are really no planar slices, and data used at a pixel or voxel location is actually more defined due to off axis beamforming of that data. Therefore, a new measurement of transaxial resolution may be utilized to judge resolution in the z axis (where lateral resolution would be in the x axis, and axial resolution would be in the y axis).

[0110] Step 604 then requires measurements be taken to determine peripheral and intracranial diameters at systole and diastole from the imaging of step 602. As discussed above, the system can measure diameters of the vessels along a given length of vessel. The length of the vessel along which measurements are obtained can be predetermined or set by the user. With 2D imaging, the longer segments or lengths of vessels may require manipulating the probe to obtain more imaging data along the lengths of the vessels. With 3D imaging, longer segments of tissue can be imaged automatically.

[0111] If both vessels are in the same view, measurements are easily taken for either systole or diastole conditions. If two separate views are required in order to get measurements, then using snapshots and cine loops along with measurements may be required. Alternatively, time stamps of acquisitions of the peripheral artery may be correlated to time stamps of acquisitions of the intracranial artery to provide measurements for both systole and diastole conditions.- 16 -SG Docket No. 10622-731.600

[0112] In some embodiments, one or more processors of the ultrasound system can automatically determine both systole and diastole measurements on either pixelated image data, or on raw data. In some examples, machine learning or artificial intelligence can be used to determine the measurements or modify / optimize the measurements based on training datasets.

[0113] The ultrasound imaging data can be used to determine the peripheral and intracranial diameters at systole and diastole, at step 604. Additionally, the ultrasound imaging data can be used to determine flow in the peripheral and intracranial artery of choice (e.g., the temporal artery and the middle cerebral artery). This can be done, for example, with doppler imaging techniques.

[0114] In Step 606 the PMA system can automatically compute flow rates, such as with Equation 1 described above. Alternatively, the flow rate can be computed and confirmed using the PMA system in Flow or Doppler mode(s).

[0115] With these parameters measured with the ultrasound probe, Equation 2 above for ICP can be solved at step 608 to calculate ICP with the peripheral and intracranial diameters and the flow in the peripheral and intracranial arteries. In some examples, the ICP can be calculated automatically by one or more processors of the PMA system.

[0116]

[0117] Therefore, this disclosure provides ultrasound imaging systems, methods, and techniques able to measure flow and systolic and diastolic vessel diameters of these representative vessels (or their equivalents) and comparing the dynamics of the peripheral vessel(s) to those of the intracranial vessel(s) to provide for a non-invasive measurement of ICP, either directly via the formulas above or potentially using / including machine learning and / or elastography that includes cranial tissue stiffness data. If machine learning is utilized, patients with an intraventricular catheter who are being monitored can be utilized to acquire the data necessary to train the machine learning algorithm(s). The multiple aperture ultrasound systems described herein are critical to this process as they can be uniquely leveraged to acquire the required pipe diameters, flow rates, and stiffness data noninvasively.

[0118] Another method that measures ICP) is provided, which can include:

[0119] Starting from Hooke’s law (stress, strain relationship):

[0120] F = K*Ax- 17 -SG Docket No. 10622-731.600

[0121] F = force

[0122] K = spring stiffness

[0123] Ax = change in length

[0124] Relating to vessel mechanics,

[0125] AP= E*ACircumferential_Strain = E * 2*7t * ADia

[0126] Where AP is the change in pressure from inside and outside the vessel (transmural pressure), E is young’s modulus (vessel stiffness) and ADia is change in diameter of vessel.

[0127] The change in pressure with blood pulse is

[0128] (BP-P_load) = E * 2* TI *ADia

[0129] BP is the change in internal vessel pressure (systolic-diastolic blood pressure) and P load is the external pressure (e.g., ICP).

[0130] As stated in this specification, two vessels can be compared with common arterial source such that BP can be considered the same in both vessels. Here we will call P inside = ICP and P outside = external load pressure on vessel outside skill (peripheral vessel). Both are unknown. BP can be measured by usual (non-ultrasound techniques) and change in vessel diameter (distensibility) using ultrasound imaging.

[0131] (BP-P_inside) = E * 2*7t*ADia_inside (BP-P_outside) = E * 2*7t*ADia_outside

[0132] Taking ratio

[0133] (BP-P_inside) / (BP-P_outside) = *ADia_inside / *ADia_outside

[0134] Unfortunately, this provides P inside (ICP) in terms of another unknown, P outside, the external load on vessel outside skull.

[0135] In another embodiment, a method is provided in which the user can apply pressure with the ultrasound probe until the outside vessel (peripheral) diameter reduces to zero (collapses) at diastolic pressure. The mechanics are similar to how blood pressure cuffs work. At this state, the external pressure equals the diastolic blood pressure. Typically, this is done by slowly increasing the pressure exerted by the probe while observing the vessel pulsing in the ultrasound B-mode image. Once the vessel collapses at diastole the pressure is held constant and B-mode loop recorded. The loop can be analyzed to measure the diameter of the vessel at systole which is used in equation below.

[0136] At this external pressure (load) condition:

[0137] P outside = P diasolic

[0138] And

[0139] The change in diameter is the diameter at systole (the loading with probe has caused diameter at diastole to be = 0)- 18 -SG Docket No. 10622-731.600

[0140] Above equation become

[0141] (BP-P_inside) / (BP-P_diatole) = *ADia_inside / *Dia_systole

[0142] The equation can be solved for P inside, ICP.

[0143] FIG. 7 is a graphic representation of flow in the vascular system, beginning at the aorta and ending in the vena cava.

[0144] Although this invention has been disclosed in the context of certain preferred embodiments and examples, it will be understood by those skilled in the art that the present invention extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses of the invention and obvious modifications and equivalents thereof. Various modifications to the above embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, it is intended that the scope of the present invention herein disclosed should not be limited by the particular disclosed embodiments described above but should be determined only by a fair reading of the claims that follow.

[0145] In particular, materials and manufacturing techniques may be employed as within the level of those with skill in the relevant art. Furthermore, reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms "a," "and," "said," and "the" include plural referents unless the context clearly dictates otherwise. As used herein, unless explicitly stated otherwise, the term “or” is inclusive of all presented alternatives, and means essentially the same as the commonly used phrase “and / or.” It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only" and the like in connection with the recitation of claim elements, or use of a "negative" limitation. Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.- 19 -SG Docket No. 10622-731.600

Claims

CLAIMS1. A diagnostic ultrasound imaging method, comprising the steps of: positioning a multiple aperture ultrasound imaging probe near a skull of a subject; transmitting one or more omni-directional unfocused ultrasound waveforms through a peripheral artery and into a brain and an intracranial artery of the subject with a transmit aperture of a multiple aperture ultrasound imaging probe; receiving ultrasound echo data with a plurality of receive apertures of the multiple aperture ultrasound imaging probe; with a processor of the multiple aperture ultrasound imaging probe, calculating one or more diameters of a peripheral artery segment and one or more diameters of an intracranial artery segment at systole and diastole from the echo data; with the processor, calculating a flow rate through the peripheral artery segment and through the intracranial artery segment; and with the processor, calculating an intracranial pressure (ICP) of the subject based at least in part on the one or more diameters of the peripheral artery segment and the one or more diameters of the intracranial artery segment at systole and diastole, and the flow rate through the peripheral artery segment and the intracranial artery segment.

2. The method of claim 1, wherein the peripheral artery comprises a temporal artery.

3. The method of claim 1, wherein the intracranial artery comprises a middle cerebral artery.

4. The method of claim 1, wherein the intracranial artery comprises an anterior cerebral artery.

5. The method of claim 1, wherein the intracranial artery comprises a posterior cerebral artery.

6. The method of claim 1, wherein a length of the intracranial artery segment is user-set.

7. The method of claim 1, wherein a length of the peripheral artery segment is user-set.

8. The method of claim 1, wherein the echo data comprises 2D echo data.- 20 -SG Docket No. 10622-731.6009. The method of claim 1, wherein the echo data comprises 3D echo data.

10. The method of claim 1, wherein the one or more diameters of the peripheral artery segment and the one or more diameters of the intracranial artery segment are calculated with a machine learning model.

11. The method of claim 1, wherein the flow rates are calculated algorithmically.

12. The method of claim 1, wherein the flow rates are measured with a doppler imaging mode of the multiple aperture ultrasound imaging probe.

13. An ultrasound imaging system, comprising: a multiple aperture ultrasound imaging probe configured for placement near a skull of a subject, the multiple aperture ultrasound imaging probe comprising a transmit configured to transmit one or more omni-directional unfocused ultrasound waveforms through a peripheral artery and into a brain and an intracranial artery of the subject, the multiple aperture ultrasound imaging probe further comprising a plurality of receive apertures configured to receive ultrasound echo data; one or more processors configured to: calculate one or more diameters of a peripheral artery segment and one or more diameters of an intracranial artery segment at systole and diastole from the echo data; calculate a flow rate through the peripheral artery segment and through the intracranial artery segment; and calculate an intracranial pressure (ICP) of the subject based at least in part on the one or more diameters of the peripheral artery segment and the one or more diameters of the intracranial artery segment at systole and diastole, and the flow rate through the peripheral artery segment and the intracranial artery segment.

14. The system of claim 13, wherein the peripheral artery comprises a temporal artery.

15. The system of claim 13, wherein the intracranial artery comprises a middle cerebral artery.- 21 -SG Docket No. 10622-731.60016. The system of claim 13, wherein the intracranial artery comprises an anterior cerebral artery.

17. The system of claim 13, wherein the intracranial artery comprises a posterior cerebral artery.

18. The system of claim 13, wherein a length of the intracranial artery segment is user-set.

19. The system of claim 13, wherein a length of the peripheral artery segment is user-set.

20. The system of claim 13, wherein the echo data comprises 2D echo data.

21. The system of claim 13, wherein the echo data comprises 3D echo data.

22. The system of claim 13, wherein the one or more diameters of the peripheral artery segment and the one or more diameters of the intracranial artery segment are calculated with a machine learning model.

23. The system of claim 13, wherein the flow rates are calculated algorithmically.

24. The system of claim 13, wherein the flow rates are measured with a doppler imaging mode of the multiple aperture ultrasound imaging probe.- 22 -SG Docket No. 10622-731.600

Images