CA2890157A1

CA2890157A1 - Novel system for emboli detection in the brain using a transcranial doppler photoacoustic device capable of vasculature and perfusion measurement

Info

Publication number: CA2890157A1
Application number: CA2890157A
Authority: CA
Inventors: Pennypacker CARL; Stuart STEIN
Original assignee: Cerebrosonics LLC
Current assignee: Cerebrosonics LLC
Priority date: 2012-10-31
Filing date: 2013-10-31
Publication date: 2014-05-08
Also published as: WO2014070993A1

Abstract

A helmet controlled and read from a remote data center enables rapid classification and triage of those having stroke-like brian issues, based upon novel uses and registering of different signal processes. Transcranial Doppler (TCD) photoacoustic imaging and other modalities rapidly generating resultory medical data is disclosed, for management of acutely brain-challenged patients on an expedited basis.

Description

INTERNATIONAL APPLICATION
FOR
NOVEL SYSTEM FOR EMBOLI DETECTION IN THE BRAIN USING A
TRANSCRANIAL DOPPLER PHOTOACOUSTIC DEVICE CAPABLE OF
VASCULATURE AND PERFUSION MEASUREMENT
Field of the disclosure [0001] The present system relates to a carotid Doppler, transcranial Doppler and/or photoacoustic system which provides remote wireless monitoring and remote control of the sensors or transducers of the subject system to and from a data/stroke center, staffed by experts, and methods that will produce a more complete picture of a traumatic event in the brain, for example, a stroke, or cerebrovascular accident (OVA) or predilection to said condition.

[0002] In the acute care setting of stroke and particularly in the prehospital situation for patients, in ambulances, helicopter, or airplanes, a strong need exists to support neurologists, radiologists and stroke teams by simultaneously obtaining rapid blood velocity measurements in neck, determination of neck and brain large blood vessel, acute blockage or narrowing, obtaining information on irreversibly injured brain versus potentially reversible brain at the stroke site.
Background of the disclosure

[0003] Stroke affects approximately 795,000 Americans each year, and approximately 6.4 million stroke survivors are now living in the United States. Although progress has been made in reducing stroke mortality, it is the fourth leading cause of death in the United States. Moreover, stroke is the leading cause of disability in the United States and the rest. of the world: 20% of survivors still require institutional care after 3 months and 15% to 30% experience permanent disability. Stroke is a life-changing event that also affects the patient's family members and caregivers. With an aging US
population tending to heavier body weights, the situation will only become more desperate.

[0004] Stroke is a global problem: In Germany, the projections for the period 2006 to 2025 showed 1.5 million and 1.9 million new cases of ischemic stroke in men and women, respectively, at a present value of 51.5 and 57.1 billion EUR, respectively. In Europe, stroke occurs in 7.2 individuals per 1000 per year (In Germany, 281,833 people have a stroke yearly) with a short term mortality rate of 12%. This rises with age and with certain races and countries, being disproportionately higher in China, Africa, and South America, where stroke mortality may be at 27%. The risk for stroke may be significantly higher in those that have not had strokes, particularly in patients with hypertension, diabetes, obesity, prior heart attack, cardiac rhythm disturbances, including atrial fibrillation, hyperlipidemia, family history of early stroke, and smoking use arguing for active prevention.

[0005] An ischemic stroke is the result of neuronal death due to lack of oxygen, a deficit that produces focal brain injury. This event is accompanied by tissue changes consistent with an infarction (tissue death caused by an obstruction to blood supply) that can be identified with neuroimaging of the brain. Strokes are usually accompanied by symptoms, but they also may occur without producing clinical findings and be considered clinically silent. Additionally, many current transcranial imaging devices are severely limited by the aberrations caused by the skull or intervening tissues. A strong need to address these matters exists.

[0006] Efficient and expeditious transfer of patients to appropriate hospitals and between hospitals, including various levels of stroke centers, prompt and accurate recognition of symptoms and neurological signs and urgent medical attention are necessary for: 1) intravenous thrombolytic therapy; 2) intra-arterial thrombolytic therapy;
3) mechanical neck and cerebral artery clot removal/dissolution to be considered, evaluated, and provided. A paucity of solutions currently have been adduced to the grave issues.

[0007] Owing to myriad logistical and other issues that lead to late delivery or no delivery of tPA to eligible stroke patients within the accepted time windows for treatment, a longstanding need exists in the art to systematize and rapidly improve these crises.

[0008] It is respectfully proposed that, the initiation of intra-arterial clot buster through a catheter by specialized professionals and/or mechanical removal of major vessel clots, particularly with devices called stent retrievers, may decrease morbidity and mortality in selected patients, particularly those patients with acute obstruction, stenosis, or occlusion of major arteries, such as the carotid arteries, middle cerebral arteries, basilar artery, or vertebral arteries. These devices or intra-arterial clot buster may lead to reopening or recanalization of acutely blocked blood vessels. The devices include catheter based clot retrieval devices, clot suction devices or mechanical clot disruption devices. Many of these devices require advancing a catheter with device through the arteries in the groin and then up to the neck and brain blood vessels. In addition but not limited to the stroke severity, the success of these therapies depend on the vessel and its size and the location of the clot within the vessel, the size of the clot within the vessel, whether the clot completely or partially obstructs the vessel, the time of the procedure after stroke onset, little attempt to quantify, integrate or register such data has eben made to date.

[0009] Although intravenous clot buster may reduce mortality and morbidity, it is not always efficacious in removing the clot blocking a vessel. Depending on vessels being treated, intravenous clot buster may give 40% partial vessel opening or recanalization and 5% complete opening. Intra-arterial clot buster may lead to 65% partial opening and 20% complete opening. Likewise, available now are a series of devices called stent retriever, i.e. Trevo0 and solitaire brands of devices. Further, intra-arterial therapy or mechanical re-opening therapies may extend the time window for treatment from 6 to 12 hours in some stroke cases (personal communication, Mao). This has been applied in some centers with positive results. However, the use of these mechanical reopening devices may have hemorrhage and additional stroke risk that must be balanced with potential benefits for patient.
Number of primary and comprehensive stroke centers

[0010] Prehospital Identification and Treatment of Stroke. The earlier identification and evaluation and initiation of therapy or place to transport has the potential for improving morbidity and mortality and in the pre-identification of patient for tPA. The time from pickup in an ambulance, helicopter, or fixed wing airplane may range from 10-15 minutes in certain urban centers with integrated ambulance services to up to 1 hour.
The time in the ambulance, helicopter, or fixed winged airplane even when short affords a window for rapid evaluation with neurological examination, to tell if a patient had a strong, yet existing symptoms are based on conscious patients. A paradigm shift in stroke care is needed as discussed.

[0011] Stroke telemedicine enhances accurate evaluation of stroke versus mimickers and differentiation from anterior versus posterior circulation strokes, as well as size of stroke and potential vessel size and identity. Determinations based on use of such resultory medical data (defined below) are key to classifying patients for exigent measures.

[0012] Without directly being part of the instant claims, contexts of treatment are important. The arrival of a stroke patient in the emergency room (ER) must be viewed as a true emergency, and the urgent care of such patients should receive priority. On arrival to the ER, identification of the patient with a potential stroke should prompt the collection of several important data points as known to artisans: 1. time the patient was last known to be neurologically normal; 2. detailed neurological exam or use of National Institutes of Health Stroke Scale (NIHSS); 3. serum glucose level; 4. medical history; and, 5. current medications.

[0013] At the time of stroke, mini-strokes, suspected strokes, or TIAs, magnetic resonance (MRI) and computed tomography (CT) of the brain (intracranial) and neck are the most employed techniques/devices used to look for blood vessel abnormalities, including stenosis, as a basis for stroke. These techniques are expensive, inaccessible, are time consuming, and not measure specific blood flows or velocities, making the story they tell incomplete in terms of brain injury status.

[0014] Important are diagnostic tools, namely: Computed tomography (CT), Computed Axial Tomography (CAT), Diffuse optical imaging (DOI) or diffuse optical tomography (DOT), Event-related optical signal (EROS), Magnetic resonance 1magmg (MRI), Functional magnetic resonance 1 magmg (fMRI), Magnetoencephalography (MEG), Positron tomography (PET) and Single photon emission computed tomography (SPECT). The PET system requires a cyclotron to produce radioactive particles.

[0015] Stroke or transient ischemic attacks (TIA) involve brain tissue damage that is permanent (stroke) or transient (TIA) from the obliteration of blood flow with reduced oxygen delivery through specific extracranial vessels, i.e. carotid arteries, cervical arteries, vertebral arteries, or intracranial vessels, i.e. middle cerebral arteries, posterior cerebral arteries due to atherosclerotic vessel change, emboli, or a combination of both.
Emboli may be gaseous or particulate. The latter may involve calcium, fat, and blood elements including platelet, red blood cells, or organized clot, i.e. thrombin with platelets or thrombin alone. The size of these embolic components is approximately 50 microns for particulate or solid emboli and 1-10 microns for gaseous emboli.
Particulate emboli may have a more important role in stroke or TIA causation, as compared to gas emboli;
this underlies a need for detection and differentiation of particulate versus gas emboli.

[0016] Cerebral emboli may be associated with cardiac, aorta, neck and intracranial vessel disease, as well as coagulation disorders and neck issues and during diagnostic and surgical procedures on the heart and the carotid arteries. Cerebral embolism can be a dynamic process episodic, persistent, symptomatic, asymptomatic, and may, but not in all cases, predispose to stroke or TIA, influenced to some degree by vessel and embolus composition and size; the latter embolic stroke, which is influenced by the vessel and its diameter to which the embolus goes.

[0017] The present system, independently, and in combination with neurological evaluation, stroke protocols, and other imaging studies may provide avenues for treatment downstream. In fact, such improvements influence the timing of delivery and appropriateness of therapeutic agents, as well as optimum location of care and services. The current system in combination with stroke telemedicine, deployed in prehospital settings, may provide physiological and clinical information that can be critical for decision making in acute stroke. Furthermore, the present device can aid the diagnosis and prevention of stroke, by remote screening of and identification of patients at risk for stroke related to intercurrent medical problems and previous stroke that will provide medical doctors and neurologists with information to implement the best treatment plan. The current system is combined with chains of acute stroke care to augment and produce a unified stroke ecosystem.
Objects and Summary of the Disclosures

[0018] Briefly stated, a helmet controlled and read from a remote data center enables rapid classification and triage of those having strong/brian issues based upon novel uses and registering of different signal process.
Transcranial Doppler (TCD) photoacoustic imaging and other modalities rapidly generate resultory medical data. A
helmet controlled and read from a remote data center enables rapid classification and triage of those having strong/brian issues based upon novel uses and registering of different signal process. Transcranial Doppler (TCD) photoacoustic imaging and other modalities rapidly generate resultory medical data is disclosed, along with a system for configuring a transcranial Doppler photoacoustic device to transmit a first energy to a region of interest at an internal site of a subject to produce an image and blood flow velocities of a region of interest by outputting an optical excitation energy to said region of interest and heating said region, causing a transient thermoelastic expansion and produce a wideband ultrasonic emission. Detectors receive the wideband ultrasonic emission and then generate an image of a region of interest from a wideband ultrasonic emission. A Doppler ultrasound signal is deployed to image the region of interest to present blood flow. Additionally, a dye can be given to visualize the brain vasculature and a perfusion measurement can be made in various regions of the brain along with the transcranial Doppler and the photoacoustic screening.

[0019] According to embodiments, there is disclosed a novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement, which comprises, in combination: at least a centralized remote data center, wirelessly communicating via high bandwidth telecom, with; an internet and/or other remotely controlled mobile and positionally x-y two-angle staged unit or system effective to support TCD and CD disposed at least in part within a helmet; means for non-invasively embracing a user's upper extremities.

[0020] According to embodiments, there is disclosed a dynamic system for registering data relating to early identification of potential patients, the improvement, which comprises, in combination: classifying resultory medical data respecting major luminal challenges during a fixed temporal window; managing exigency steps based upon said resultory medical data; directing communications to essential personnel and stations at an appropriate facility selected from the group of a primary and a comprehensive stroke center; facilitating data calculation and analysis of major carotid, vertebral and cerebral occlusions; and, confirming transfer of resultory medical data upon which classifications are based.

[0021] According to embodiments, there is disclosed a method of configuring an ultrasound array to transmit a beam pattern sufficient to insonate a region of interest at an internal site of a subject, said method comprising the steps of: a) providing an array of ultrasound transducer elements; b) outputting a beam pattern from said array of ultrasound transducer elements to insonate a region of interest at an internal site in a body sufficiently large that the beam pattern comprises a multi-beam pattern, insonating multiple receiver elements over a substantially simultaneous period by directing energy produced by said array of ultrasound transducer elements into said region of interest in said body, and adjusting an amplitude of energy output by said array of transducers to cause the beam pattern output to have a generally flat upper pattern and nulls in a grating lobe region; and, c) introducing a phase shift of the beam pattern output from said array of ultrasound transducer elements, wherein a degree of phase shift increases as a distance increases from a central output area of said array of ultrasound transducer elements.

[0022] According to embodiments, there is disclosed a method of configuring an ultrasound array to transmit a beam pattern sufficient to insonate a region of interest at an internal site of a subject, said method comprising the steps of: a) providing an array of ultrasound transducer elements; b) outputting a beam pattern from said array of ultrasound transducer elements to insonate a region of interest at an internal site in a body sufficiently large that the beam pattern comprises a multi-beam pattern, insonating multiple receiver elements over a substantially simultaneous period by directing energy produced by said array of ultrasound transducer elements into said region of interest in said body, and adjusting an amplitude of energy output by said array of transducers to cause the beam pattern output to have a generally flat upper pattern and nulls in a grating lobe region; and, c) introducing a phase shift of the beam pattern output from said array of ultrasound transducer elements, wherein a degree of phase shift increases as a distance increases from a central output area of said array of ultrasound transducer elements.

[0023] According to embodiments, there is disclosed a method for operating an array of ultrasound transducer elements, wherein the element spacing in the array is greater than, equal to or less than a half wavelength of the ultrasound energy produced by the elements, and wherein the array is used differently in transmit and receive modes, comprising: forming a transmit beam from a position external to a region of interest encompassing a plurality of receive beams and initially acquiring a signal by insonating a target region comprising multiple receive beam positions over a substantially simultaneous period; receiving data from the multiple receive beam positions of the array; combining the received data in a processor; locking onto the receive beam and the point(s) producing a peak signal; and correcting for motions in the target region by periodically forming multiple receive beams and re-acquiring the peak signal.

[0024] Methods and apparatus of the present system generally involve using ultrasound transducers coupled to a device, to identify, observe, and measure vasculatures in the brain. In each minute of a stroke, over a million neurons die, and over a billion synapses die. Said device thus comprises the capability to be controlled and read from a remote Data Center, thus enabling the rapid diagnosis of the type and severity of stroke a patient may be undergoing in an emergent situation. The diagnosis can then be sent to those aiding the patient, to correct the level of care for continual treatment and evaluation and care of the patient. It is a further object of this system that remote operators can control positions of ultrasound transducers, which are mounted on motors with encoding system. A further object of this system is that novel signal processing will allow identifying the precise location of ultrasound signal in the brain vasculature with respect to a stable coordinate system; such signals are added together from the same spot of the brain, suppressing the "noise" introduced by operator or other disturbing motions, and enable much smaller vasculature to be observed and measured. A further object of this system is that remote neurotechnicians and neurologists can visualize in real time or data from a rapid archive the results of the TCD scan of major vasculature, and, for example, recommend transport to a comprehensive stroke center. A further object of this system is that different types of strokes ¨ hemorrhagic versus ischemic, for example, can be visualized and understood by Data Center staff, and appropriate measures taken. Furthermore, many other brain disorders caused by incomplete vascularization of the brain, such as Traumatic Brain Injury or Vascular Dementia can be observed and diagnosed by this system in consort with Data Center staff.
Brief Description of the Drawings

[0025] The above and other exemplary features and advantages of certain exemplary embodiments of the present system will become more apparent from the following detailed description of certain exemplary embodiments thereof when taken in conjunction with the accompanying drawings, in which:

[0026] FIG. 1 illustrates a flow diagram of a system according to a proffered embodiment, namely species of an invention in accordance with an aspect of the system, intended as descriptive and not limiting.

[0027] FIG. 2 illustrates a flow diagram overview of relationships between Internet-Control Actuators as a sub-combination in accordance with aspects of the system of the instant disclosure.

[0028] FIG. 3 is one-dimensional cross-sectional view illustrating details of the Actuators/Positioning System for Transducers according to embodiments of the present invention.

[0029] Fig. 4A illustrates a graphical view of TCD/Actuator Module Placements on a Patient's Head and their communication with a Remote Control System.

[0030] Fig. 4B illustrates a 3D view of an embodiment of the patient-end of the instant system with TCD apparatus.

[0031] Fig. 5 illustrates an exemplary hierarchy chart depicting the development of a stable skull via the control box in accordance with an aspect of this system.

[0032] Fig. 6 is an exemplary hierarchy chart illustrating the development procedure of a high-resolution 3-D model of the brain/neck arterial vasculature in accordance with an aspect of this system.

[0033] Fig. 7 is an exemplary decision tree illustrating the process involved when incorporating the Transcranial and Carotid Doppler Device in an acute stroke situation.
Detailed Description

[0034] The present inventors have assembled a system which dynamically registers data identification of potentially lumen-challenged patients. "Time is brain,"
or, the more expedient the intervention, the stronger likelihood of mitigating, extenuating, or preventing deleterious impacts of stroke on cognitive functions and abilities.
The faster of the determination as to treatment, the higher the chance that tPA/lytic or mechanical intervention can be used.

[0035] Only 27.4% of patients that are given tPA receive this within the first hour of arriving at the emergency room but in addition to the time of onset and transport emergently; therefore, because of the delays, outcome may be compromised and death risk increased. Many patients with stroke do not get tPA or clot buster within the acceptable 4.5 hour time range, early in that time period, or do not get tPA
at all. Certain hospitals in the United States and Europe can achieve Emergency room (door) to needle time of 20 to 38 minutes for patients to receive tPA (references if needed), which is considered best practice. In sum, has a narrow temporal window to be managed.

[0036] Current systems need to be improved. First, a complex set of events and steps need to occur. These include: 1) EMS Pre-Notification; 2) Stroke Toolkit with all things that need to be done; 3) Rapid Triage and Stroke Team Notification; 4) A
Single telephone or pager Call Activation System; 5) *Transfer Directly to CT scan to evaluate the brain for stroke or a bleed; 6) Rapid CT and warranted other Brain Imaging; 7) Rapid blood evaluation for blood clotting profiles and other essential measures; 8) Premixing of the clot buster for potential therapy; 9) Rapid TPA Access -store TPA in ED/radiology, start in; imaging suite; 10) Team approach; and 11)*Prompt data feedback to physicians that evaluate the patient and must make the decision about TPA.

[0037] Patients require a CT scan of the brain to evaluate for stroke and specifically to see if there is brain hemorrhage, which is an absolute criteria for not using clot buster.
6.2% of all patients that receive clot buster may have a secondary and very debilitating hemorrhage. This may increase with other medical conditions or drugs that an individual patient will have This is one of the most important reasons for the initial CT
scan but also the very detailed evaluation by strict criteria of all patients. Absolute exclusions are factors related to the patient that will increase hemorrhage risk, include very high blood pressure, diabetes, or anticoagulation therapy. Once hemorrhage occurs, the morbidity and mortality rise significantly and negate positive effects of clot buster.

[0038] The value of the instant system is in the early identification of potential patients with major neck or brain artery acute occlusions or blockages in the ambulance, helicopter, or fixed window, that can then be considered for rapid transport to a comprehensive stroke center or primary stroke center where both have quality interventional radiology or interventional neuroradiology for clot dissolution or removal.
Transcranial Doppler

[0039] Transcranial Doppler (TCD) is a test that measures the velocity of blood flow through the brain's blood vessels. Used to help in the diagnosis of emboli, stenosis, and the like. Transcranial Doppler provides a basis, taken together (with other tests) for putative emboli and potential treatment planning and initiation. An embodiment of the present system allows for multiple brain blood vessels can be evaluated simultaneously and the skull can be sampled at multiple points without concern for skull bone interference.

[0040] Blood flow velocity is recorded by emitting a high-pitched sound wave from the ultrasound probe, which then bounces off of various materials to be measured by the same probe. A specific frequency is used (usually close to 2 MHz), and the speed of the blood in relation to the probe causes a phase shift, wherein the frequency is increased or decreased. This frequency change directly correlates with the speed of the blood, which is then recorded electronically for later analysis. Normally a range of depths and angles must be measured to ascertain the correct velocities, as recording from an angle to the blood vessel yields an artificially low velocity.

[0041] Because the bones of the skull block the transmission of ultrasound, regions with thinner walls insonation windows must be used for analyzing. For this reason, recording is performed in the temporal region above the cheekbone/zygomatic arch, through the eyes, below the jaw, and from the back of the head. Patient age, gender, race and other factors affect bone thickness, making some examinations more difficult.
Resultory Medical Data, as defined for the purpose of this application includes TCD.
Photoacoustic Spectroscopy

[0042] Photoacoustic spectroscopy is the measurement of the effect of absorbed electromagnetic energy (particularly of light) on matter by means of acoustic detection.
The discovery of the photoacoustic effect dates to 1880 when Alexander Graham Bell showed that thin discs emitted sound when exposed to a beam of sunlight that was rapidly interrupted with a rotating slotted disk. The absorbed energy from the light is transformed into kinetic energy of the sample by energy exchange processes.
This results in local heating and thus a pressure wave or sound. Later Bell showed that materials exposed to the non-visible portions of the solar spectrum (i.e., the infrared and the ultraviolet) can also produce sounds.

[0043] Photoacoustic imaging is based on the photoacoustic effect. In photoacoustic imaging, non-ionizing laser pulses are delivered into biological tissues (when radio frequency pulses are used, the technology is referred to as thermoaccoustic imaging).
Some of the delivered energy will be absorbed and converted into heat, leading to transient thermoelastic expansion and thus wideband (e.g. MHz) ultrasonic emission.

[0044] The generated ultrasonic waves are then detected by ultrasonic transducers to form images. It is known that optical absorption is closely associated with physiological properties, such as hemoglobin concentration and oxygen saturation.

/ / /
Vasculature and Perfusion Measurement

[0045] Perfusion is the process of delivery of blood to a capillary bed in the biological tissue. Vasculature and perfusion measurements in the Brain perfusion (more correctly transit times) can be estimated with contrast-enhanced computed tomography. To get a better representation of the blood flow in the brain, a dye is injected into the patient to enhance visualization of the suspect area. Resultory medical data likewise includes this information.

[0046] Therefore, what is needed is a medical device with TCD, Photoacoustic, and Fluorescent Dye for determination of Cerebral Blood Flow, Oxygenation and is capable of Diffusion/Perfusion Match/Mismatch which would aid in the determination for tPA
assistance. It is important that a system and method is deployable in a rural, urban, clinic, third world or be an inpatient device for Brain Blood Flow, Vessel Definition, Emboli Detection and Brain Metabolism.

[0047] Photoacoustic imaging is a well-known art that uses a light beam, typically a laser, to deposit energy molecules and absorption bands the converted energy from the laser to be reemitted as thermal energy to create an expansion of the materials around the molecule, and create a pressure wave. Such pressure waves are in vivo, and cause mechanical disturbances of the media, and manifest themselves partially as broadband ultrasound. Ultrasound typically permeates and scatters much less than optical light, so photoacoustic imaging then gives one the capability to resolve structures with much higher resolution than simple measuring the back-scattering of light, particularly in soft tissues. With respect to photoacoustic imaging in the skull, one is limited by the scattering of ultrasound in the skull. For skull windows, this might result in smearing of the ultrasound resolution by a typical thickness parameter of the skull window, which may be a few millimeters.

[0048] Phased Array: Phased Array Ultrasound is a well-known art that enables the use of multiple transducers to be pulsed and readout independently. Having an array of such devices enables beam steering, beam forming, and higher resolution imaging upon return of the reflected/scattered ultrasound. due to the larger receiving aperture.
The beam can be electronically steered, and then read back for that part of space interrogated by the smaller beam size enabled by the phased array beam-forming algorithms. Such devices are used in Medical Imaging and in many industrial applications. Typically, because of the much higher resolution afforded by MRI
and CT
scanning devices, phase array ultrasound has not been used in the brain.
However, when larger structures are imaged, such as major vasculature, and superb resolution is not desired, phased array ultrasound is adequate. In particular, phased array ultrasound can fit into a small box, and be part of an ambulances or Emergency Department or other medical settings equipment, as compared to the room-size MRI's and CT
scanning systems. In common use, phased array has been used to look at brain blood flow velocities.

[0049] Types of imaging in stroke: the CT scan is essential in the evaluation for acute treatment of stroke, as it is used to rule out a brain bleed, and can in some cases be used to see a stroke. A stroke that appears on CT may represent a completed stroke and therefore, thrombolytic therapy is not warranted as there is little chance of recovery of the dead tissue and brain hemorrhage risk is increased in this context if thrombolytics are given. By registering such resultory medical data, classifications can be better made.

[0050] When CT angiography or MR angiography cannot be performed, for any reason, ultrasound techniques with definition of the neck arteries, carotid and vertebrals, can be done with carotid Doppler. TCD can be performed to obtain physiological information about brain blood vessels. These studies are usually not available emergently in the United States, but may be primary parts of the acute stroke evaluation in Europe, where CT angiography, MR scans, and MR angiography may not be available. At any hospital or stroke center, the exams performed are variable and may be idiosyncratic. Both types of scans are very useful is showing collateral blood vessel flow that may determine how robust the patients vessels might be for protecting against severe damage.

[0051] In the current embodiment, carotid dopplers, including Doppler and B
mode wave insonation will be recorded with previously validated patch carotid Doppler transducers affixed to the bilateral carotid arteries. The transducer will be a convex transducer as opposed to linear transducers. As such, a single sampling point will be used as opposed to multiple sampling points for proximal, middle, and distal carotid arteries. Raw imaging data will be sent wirelessly to the data and stroke center, processed there, and analyzed similar to the transcranial Doppler ultrasound.

[0052] The instant system provides rapid alternatives of independent and complimentary value to other imaging techniques for evaluating acute brain and neck blood vessel occlusion or narrowing and for potentially revealing areas of dead brain tissue versus potentially viable injured tissue contiguously.

[0053] With reference now to Figure 1 through Figure 4, a novel system according to the instant teachings, is depicted in an overview, along with select detailed aspects.
Ultrasound on areas of a patient's skull and carotid artery are done using Helmet Device 106, and information gathered from the ultrasound 108 and 110 are transmitted wirelessly over Internet 104, to a Remote Data Center 100. Helmet Device 106 is capable of operating in an ambulance, helicopter, airplane, emergency room, or the like.

[0054] Uniquities of the Remote Data Center 100 include that skilled technicians and doctors who well understand the hardware and software described here can be on call 24 hours a day, and respond to any stroke emergency, anywhere in the world.
High-speed wireless capability exists for most modern ambulances and Emergency Rooms, with data rates of many megahertz per second available. With the ability to visualize and analyze images of patient 112 that are captured and sent wirelessly from helmet device, physicians at Remote Data Center 100, are then able to alert and direct the operators that are currently in person at patient's 112 side.

[0055] In an exemplary embodiment, the helmet may have various configurations so long as the device has the ability to comprise actuated ultrasound transducers.

[0056] Referring now to Figure 2, a simpler version of the system overview in Figure 1, with a more detailed depiction of helmet device 106 coupled with internet-controlled Transducers 300, is shown. Helmet apparatus 106 contains transducers and actuators 300, controlled by micro-motors 250, and is mounted around the patient's 112 head (See, Figure 4B). The transducers 300 are coupled to the micro-motors 250, allowing the position and angle of the transducers 300 to be controlled remotely over the internet, from the Data Center for example. The transducers and actuators 300 are driven by pulsed, oscillating currents from TCD control box 200, which emits ultrasound waves. The TCD control box 200 can be turned on remotely. Operators (whether remotely or at the site) will move TCD transducers 300 until they detect return Doppler signals from TCD transducers 300.

[0057] A map of the local thickness of the skull can be made by moving the TCD

transducers 300 in x and y directions in a plane parallel to the local surface of the skull.
The ultrasound waves travel into an impedance matching system (shown later in FIG.
3), and then into the skull. On entering the skull, some ultrasound is reflected, and when the ultrasound exits the brain and enters the soft tissue of the skull, ultrasound is reflected again. The time between these two pulses can be converted into a distance.
The speed of sound in the skull is known to be 3,360 meters/second, and multiplying the time interval between these pulses by the speed of sound gives the local thickness of the skull. Such thicknesses is recorded and put into an array in computer memory, or a file on disc, or other media that then describes skull thicknesses. This helps establish an absolute reference frame for all work and in addition, alerts the operator as to where the thinnest parts of the skull are for easier insonification.

[0058] Generally speaking, a computer at the ambulance or emergency room or remote site 100 allows significant control of the TCD pulses, pre-processing of TCD
data, aligning the TCD data to an absolute reference frame, and also relaying real-time images of the Doppler signal, synchronized with the pulse and the estimated depth and position of the insonated vasculature.

[0059] In another exemplary embodiment, TCD control box 200 contains a computer/Actuator computer or like means for viewing and sending images and information obtained from the transducers to the remote center, as known to those of general skill in the art.

[0060] Referring now to Figure 3, a detail of the stage that enables movement of transducer 300 on soft disposable 306 is depicted. The movement of the transducer 300 on the soft disposable matches impedance of ultrasound, and allows the transducer 300 to travel on a plane parallel to the skull, under remote control from the Data Center 100. Transducer 300 can be pointed by a two-angle pointing system 304 that is carried by x-y stage 302. Impedance matching insert 306 is made of low friction material, with extremely low friction comparable to Teflon TM brand of ePTFE, so ultrasound transducer 300 can move along impedance matching insert 306 without jamming. In addition, impedance matching insert 306 enables ultrasound transducer 300 to point at large angles to the normal vector of the skull, enabling the remote technician to thoroughly search for arteries.

[0061] According to another exemplary embodiment, the impedance matching insert 306 can also be disposable.

[0062] Referring now to Figure 4a, an overview of TCD/Actuator module placements on a patient's 112 head is depicted. The overview is depicted without the frame or outer helmet device structure, so the placement of the ultrasound transducers 300 can be clearly seen. Each actuator/transducer 300 is placed together inside of a transducer-actuator box 202, 204, 206, and 208.

[0063] According to embodiments as shown in this view, four transducer-actuator boxes are depicted; however there are 7 in total¨the transducer-actuator box pictured around left eye 202, left ear 204, and left neck/carotid area 208, each have a similar transducer-actuator box in similar locations on the other side/right side of the face.
Each transducer-Actuator box controls an actuator/motor 250 that can move the ultrasound transducer 300 in two dimensions and also point in two angles, all the while staying in contact with the flexible impedance matching insert 306. Signals sent to control the transducers 300/actuator motors 250 from the Remote Data Center 100, are transmitted wirelessly 102 to a radio or receiver in the ambulance in digital form, and then are routed to the TCD control box 200 in the ambulance. The TCD control box 200 then transmits and receives signals to the transducers 300 and the actuators, enabling the remote operator to visualize the output of the TCD at a given position and angle.

[0064] Referring now to Figure 4b, a 3-D view of the Trans-Cranial Doppler with remote control device is depicted. The device consists of a rigid base shell or helmet 133 that is either placed around the patient's 112 head or the head is placed into the base shell 133 while the base shell 133 is affixed to the supporting surface upon which the patient 112 is laying. The main material for the base shell (base shell number) is a plastic, metal, or other like material that can be produced by thermoforming, injection molding, casting or other like means. The base shell 133 creates the framework for the helmet. Likewise, silicone, for example, as disclosed in U.S. Letters Patent 8,449,565, may be used, said patent being incorporated expressly herein by this reference, as if the contents of the same were set forth herein in their entirety.

[0065] A conformable interior material for base shell 133 allows a variety of head sizes and shapes to be accommodated for proper fit. This conformable material may be an open-cell or closed-cell foam, or an inflatable network of chambers, or a combination of both. Two pivoting shell members (113, 115) (hinged at E) 404 that lock together to form the front of the helmet, are held open during the insertion of the patient's 112 head, by a spring load or other like structure/device 404 (not shown). These members (113, 115) are then manually closed by a technician and locked together 402 to form the helmet's fully encompassing shell. At this time the basilar artery and vertebral artery transducer 206 and temporal bone window transducers 204 are in initial contact with the patient 112. Two separate modules are installed using a snap insertion interface that places the eye ultrasound transducers 202 and Carotid ultrasound transducers 208 over the eyes and over the carotid arteries. The ultrasound transducers over the carotid arteries 208 are applied using pressure sensitive adhesive in the appropriate locations, similar to EKG electrodes. These modules and members are of the same material construction as the base shell (113).

[0066] The helmet apparatus holds an array of seven custom Doppler transducers in lateral symmetry of the head, of which the two Carotid ultrasound transducers 208 and two temporal bone window ultrasound transducers 204 are bilateral, and of which the two eye ultrasound transducers 202, two temporal bone window ultrasound transducers 204, and basilar artery and vertebral artery ultrasound transducer 206 are remotely controlled in X-Y translation across the surface of the skull, pressured against the patient's 112 head in the Z direction at an appropriate pressure, pitch, and yaw angle rotation to aim the Doppler beam. These movements are carried out by a set of motor actuators 250, specified schematically in the drawing as TCD/Actuator Motor modules 250. The two carotid artery transducers 208 do not contain this translational control.
The two eye transducers 202 and two carotid transducers 208 may be located on a more flexible substrate of the modules they are attached to, in order to prevent harmful levels of pressure applied to the eyes and the carotid arteries. In another exemplary embodiment, the two eye transducers 202 and two carotid transducers 208 may also be attached with adhesive. The wiring for the motor modules 250 and the transducers 300 is routed through the helmet to the base of the shell, where the connection interface to the power supply and data output modem 400 is located. The separate helmet members have electronic connections in the snap interface to route power and data through the helmet's wiring.

[0067] The power supply and all data processing and transmission is done outside of the helmet to minimize the weight and complexity of the helmet. Each transducer can be used in series, activating only one at a time, or can be used in parallel to establish reference frames and use advanced signal processing, as described above.
Alternatively, each set of transducers is operated jointly to be able compare and contrast signals. The operator is a skilled TCD technician or medical doctor in a command center that has a data link to the helmet attached to the patient 112 in the ambulance or other remote facility. The system will allow the remote operator to give real-time feedback on the patient's 112 cranial circulation status.

[0068] Referring now to Figure 5, a hierarchal chart illustrating the development procedure of a stable skull/neck reference frame independent of the helmet device 106/patient's 112 motion and phenotypic differences is depicted. This chart illustrates the flow of data from the transducers 300 to the TCD control box/computer 200 system, so that a stable reference frame of the patient's 112 skull can be developed.
After an initial identification of the position of the skull with respect to the skull map using both x-y scans 502, the control box 200 system further identifies the location of the transducers with respect to the other transducer 504. Next, the control 200 system receives the x-y scan information (transducer measurement information) 506, and uses the information to stabilize, i.e. measure and maintain its best position 508. The reference frame is set by the arrival times of ultrasound from the other transducers on the head;
this enables freedom from mechanical disturbances, as for example in a bouncing ambulance, and also enable a reference frame that can be determined to sub-millimeter accuracy. The novelty of this "good positioning" overcomes traditional "transducer-movement noise,"
which limits the size of vasculature or other structures to be larger than the rms of the ultrasound transducer movement time

[0069] Referring now to Figure 6, a decision tree showing the procedure used to develop a higher resolution 3-D model of a brain/neck arterial vasculature is depicted.
The tree shows the algorithms for reduction of the signals to a high-quality set of images of brain arterial vasculature. These algorithms are coupled to the ultrasound transducer position as discovered by its position relative to skull vasculature, and also the arrival times of signal from other transducers that are depicted in Figure 5. The TCD
control box 200 system receives signals from one ultrasound transducer/position in the brain and averages it 602. Then TCD control box 200 system accumulates consecutive Doppler signals from each position in the brain, and co-adds them 604. If there is signal present, the signal should grow proportional to the number of insonation return signals captured, and the noise should only grow as the square root of the number of insonations captured. In particular, if the ultrasound transducers are stepped at 1/10 of their resolution and high quality data is accumulated, then a mathematical fit (least squares or other minimization algorithm) can be made between the measured data and the underlying assumed vasculature which could give rise to such a number of dithered data images 608. In particular, for large vessels, skull vasculature is well known and easy to detect, and good starting point models can be estimated and used as an initial system to fit to 610. This algorithm is flexible enough to allow discovery of complete occlusions or hemorrhages, thus the fit also accommodates such medically important circumstances.

Claims

1. A novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement, which comprises, in combination:
at least a centralized remote data center, wirelessly communicating via high bandwidth telecom, with;
an internet and/or other remotely controlled mobile and positionally x-y two-angle staged unit or system effective to support TCD and CD disposed at least in part within a helmet means for non-invasively embracing a user's upper extremities.

2. The novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement of Claim 1, wherein multiple brain blood vessels can be evaluated simultaneously and the skill can be sampled at multiple points without concern for skull bone interference.

3. The novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement of Claim 2, said multiple points further comprising insonation regions selected from the temporal regions above the cheekbone/zygomatic arch;
through the occipital orbits;
below the jaw; and/or, from the back of the head.

4. The novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement of Claim 3, embodied in apparatus having TCD, photoacoustics and fluorescent dye for determination of cerebral blood flow;
further comprising oxygenation and capability of diffusion/perfusion matching and mismatching to provide resultory medical data to support assessment of a patient for tPA treatment.

5. The novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement of Claim 4, wherein rapid alternatives of independent and complimentary value to other imaging techniques for evaluating acute brain and neck vessel occlusion or narrowing and for potentially revealing areas of dead brain tissue versus potentially viable tissue contiguously.

6. The novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement of Claim 5, said centralized remote data center further comprising, in combination:
TCD and CD data visualization and probe-reading software;
an ambulance alert/communication system;
at least a patient electronic records system;
image visualization and alaysis software to enable scientific visualization of raw data from TCD and CD;
expert review of data; and, communication protocols and hardware to support definition of care and locus of care.

7. In a dynamic system for registering data relating to early identification of potential patients, the improvement, which comprises, in combination:
classifying resultory medical data respecting major luminal challenges during a fixed temporal window;
managing exigency steps based upon said resultory medical data;
directing communications to essential personnel and stations at an appropriate facility selected from the group of a primary and a comprehensive stroke center;
facilitating data calculation and analysis of major carotid, vertebral and cerebral occlusions; and, confirming transfer of resultory medical data upon which classifications are based.

8. The dynamic system of claim 7, wherein the classifying step uses resultory medical data to distinguish hemorrhagic from ischemic stroke due to the widely varying velocity fields observed with one of super resolution and width of the signal within one voxel (resolution element).

9. The novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement of Claim 6, further comprising single channel or phased array transducers mounted on x-y position stages and two-angled angular pointing stages that are remotely controlled from the Internet and effective to return doppler shifted signals of blood flow from brain vasculature to a remote technician.

10. The novel system for emboli detection in the brain using a transcranial Doppler photoacoustic device capable of vasculature and perfusion measurement of Claim 9, wherein images of a patient's brain vasculature are taken and put into an EMR
system, and then compared and subtracted voxel by voxel after a brain-challenging event to determine nature and severity of the stroke.

11. A method of configuring an ultrasound array to transmit a beam pattern sufficient to insonate a region of interest at an internal site of a subject, said method comprising the steps of:
a) providing an array of ultrasound transducer elements;
b) outputting a beam pattern from said array of ultrasound transducer elements to insonate a region of interest at an internal site in a body that is sufficiently large that the beam output pattern comprises a multi-beam pattern, insonating multiple receiver elements over a substantially simultaneous period by directing energy produced by said array of ultrasound transducer elements into said region of interest in said body, and adjusting an amplitude of energy output by said array of transducers to cause the beam pattern output to have a generally flat upper pattern and nulls in a grating lobe region;
and, c) introducing a propagation time delay of the beam pattern output from said array of ultrasound transducer elements, wherein the propagation delay increases as a distance increases from a central output area of said array of ultrasound transducer elements.

12. The method according to claim 11, wherein the transmission of said array of transducer elements is configured in step b) such that the beam pattern output by said array of transducer elements appears to propagate from a point source having a focal distance located behind said array of transducer elements when viewed from said region of interest.

13. The method according to claim 11, wherein step b) further includes adjusting a duty cycle of one or more pulses output by at least one transducer element of said array of transducer elements.

14. The method according to claim 11, wherein step b) includes adjusting a quantity of pulses output by at least one transducer element of said array of transducer elements.

15. The method according to claim 12, wherein step b) also includes adjusting a quantity of pulses output by said at least one transducer element of said array of transducer elements.

16. The method according to claim 11, wherein said array of transducer elements comprises at least one of an 8x8 array and a 10x30 array.

17. A method of configuring an ultrasound array to transmit a beam pattern sufficient to insonate a region of interest at an internal site of a subject, said method comprising the steps of:
a) providing an array of ultrasound transducer elements;

b) outputting a beam pattern from said array of ultrasound transducer elements to insonate a region of interest at an internal site in a body sufficiently large that the beam pattern comprises a multi-beam pattern, insonating multiple receiver elements over a substantially simultaneous period by directing energy produced by said array of ultrasound transducer elements into said region of interest in said body, and adjusting an amplitude of energy output by said array of transducers to cause the beam pattern output to have a generally flat upper pattern and nulls in a grating lobe region; and, c) introducing a phase shift of the beam pattern output from said array of ultrasound transducer elements, wherein a degree of phase shift increases as a distance increases from a central output area of said array of ultrasound transducer elements.

18. The method according to claim 7, wherein the transmission of said array of transducer elements is configured in step b) such that the beam pattern output by said array of transducer elements appears to propagate from a point source having a focal distance located behind said array of transducer elements when viewed from said region of interest.

19. The method according to claim 7, wherein step b) further includes adjusting a duty cycle of one or more pulses output by at least one transducer element of said array of transducer elements.

20. The method according to claim 7, wherein step b) includes adjusting a quantity of pulses output by at least one transducer element of said array of transducer elements.

21. A method for operating an array of ultrasound transducer elements, wherein the element spacing in the array is greater than, equal to or less than a half wavelength of the ultrasound energy produced by the elements, and wherein the array is used differently in transmit and receive modes, comprising: forming a transmit beam from a position external to a region of interest encompassing a plurality of receive beams and initially acquiring a signal by insonating a target region comprising multiple receive beam positions over a substantially simultaneous period; receiving data from the multiple receive beam positions of the array; combining the received data in a processor; locking onto the receive beam and the point(s) producing a peak signal; and correcting for motions in the target region by periodically forming multiple receive beams and re-acquiring the peak signal.