Patent Application
20210259666
The present invention belongs to the field of medical imaging for the non-invasive real time determination of a cardiovascular blood pressure.
Diseases including congestive heart failure (CHF), abdominal aortic aneurysm (AAA), pulmonary artery hypertension (PAH), are a major cause of premature death. There is a desire to be able to provide an advantageous monitoring of intravascular and/or intracardial blood pressure, including continuous monitoring. Based on such blood pressure measurements, diagnosis and treatment of patients can be based on a unique level, preventing substantial populations of patients from premature death.
In general, implantable sensors used for such monitoring are introduced via endovascular techniques. Such invasive measurement of intra-cardiac pressure is desired to be minimized due to complexity of the procedure and related patient risk.
There are two types of implantable sensors. Active implantable sensors that need a rechargeable energy source, which is undesired and related to a number of apparent disadvantages. Passive implantable sensors which are typically electromagnetic, providing an electromagnetic signal when irradiated from the external to the human body source of electromagnetic energy mainly in radio frequencies (RF). These sensors have a considerable drawback due to the locality of their position and ability to measure the pressure only in their circumference, also these sensors have electronics incorporated and have thus related disadvantages, such as questions of biocompatibility, size or reliability of the implanted sensor over time. Moreover, while a part of the RF energy is absorbed by the implanted RF sensor, parts of the RF energy are absorbed by the body which may cause potential problems in living organisms. Energy transmitted from outside the body may be converted in these implants to power the electronics, make measurements and transmit measurement results back to the outer detecting system. Such detecting system, positioned external to the human body registers the electromagnetic field irradiated in its turn by the circuit of the implanted sensor.
An example of electromagnetic sensors is described in the U.S. Pat. No. 7,245,117 B1 with the title “Communicating with implanted wireless sensor”, the resonant frequency of a sensor is determined for energizing the system to burst the RF energy at predetermined frequencies and amplitudes. A similar technology is described in the U.S. Pat. No. 8,894,582 B2.
Cardiovascular ultrasound measurements are known, but restricted to either catheter based ultrasound transceivers introduced into the body, or imaging and Doppler ultrasound measurements. Blood pressure in peripheral vessels may be measured non-invasively from the outside of the body using ultrasound. However, calibration to actual pressure values of such ultrasound-based methods is complex and not always reliable. Moreover, such methods cannot selectively measure pressure at specific depths and places in the body, e.g. in the aorta or the heart. Other, non-invasive techniques include methods to examine dimensions of blood vessels, or methods based on examining blood flow and are based on Doppler ultrasound or other ultrasound imaging methods, as disclosed, for instance, in U.S. Pat. Nos. 5,411,028, 5,477,858 A, 5,544,656, 6,814,702 B2, 5,724,973 A, US 20140081144 A1, EP 1421905 A1, U.S. Pat. No. 7,128,713 B2, WO 2007087522 A2, US 20080119741 A1, U.S. Pat. No. 7,736,314 B2, US 20130197367 A1, or US 20130006112.
For example in U.S. Pat. No. 5,520,185 A with the title “Method for recognition and reduction of blood speckle in blood vessel imaging system”, a method for enhancing an intravascular ultrasound blood vessel image system is disclosed. It is explained how ultrasound echoes representing vessel walls are distinguished from ultrasound echoes from blood flow by using a classifier which employs the mean and variance of the raw data of greyscale intensities as acquired directly from an ultrasound scanner-detector.
In U.S. Pat. No. 5,800,356 with the title “Ultrasonic diagnostic imaging system with Doppler assisted tracking of tissue motion”, a method for tracing the border of tissue through temporarily acquired scan lines using velocity information corresponding to the tissue edges to trace the denoted border is disclosed.
In U.S. Pat. No. 6,258,031 B1 with the title “Ultrasound diagnostic apparatus”, the velocity of a blood flow and velocity of a blood walls at the same time are measured by an ultrasound with phase detecting.
In US 20090171205 A1 with the title “Method and system for locating blood vessels”, a method utilizing the direct ultrasound sounding for detecting the blood vessels and precisely determining of their depth and diameter is disclosed.
In U.S. Pat. No. 8,469,887 B2 with the title “Method and apparatus for flow parameter imaging”, a method using pulse-wave spectral Doppler imaging allowed to obtain an ultrasound image as a sectional image of the blood vessel, including the inner and outer walls.
Other methods and systems for blood pressure measurements in the blood vessels using Doppler ultrasound imaging are disclosed in: U.S. Pat. No. 5,749,364 A1, WO 20010000 A9, US 20070016037 A1, US 20050015009 A1, US 20140180114 A1, US 20140148702, U.S. Pat. No. 8,968,203 B2, US 20150289836.
In US 20150230774 A1 with the title “Blood pressure monitor and method”, non-invasive continuous real-time monitoring of an arterial blood pressure is disclosed using Doppler probes for systolic and diastolic blood pressure.
In the patent U.S. Pat. No. 7,404,800B2 a hybrid LVEDP monitor is disclosed. The patent refers to unspecified non-invasive pressure measurement devices (“barographs”), yet does not disclose how they produce the “pressure waveform” that is therein used for subsequent analysis and unlike current disclosure does not rely on multi-dimensional image processing.
The above discussed non-invasive ultrasound or Doppler ultrasound methods for the examination of the blood vessels have a number of explicit deficiencies and it is desirous to overcome each of these deficiencies, alone or in combination. Deficiencies include but are not limited to the below:
1. Reproducibility and accuracy of the examination of the blood vessel is highly dependent on the correct orientation of the ultrasound beam's propagation direction (the axis of the ultrasound transducer) relatively to the vessel's longitudinal axis being interrogated. The speed of blood flow is measured by converting of the value of the shift of the Doppler frequency if using the Doppler equation:
V=(c×Δf)/(2f0×cos α),
where V is the velocity of the blood flow, c is the speed of sound in the tissue, f 0 is the initial frequency of the signal, and α is the angle between the direction of the blood flow and the axis of the ultrasound beam. The angle α strongly affects the value of the measured Doppler frequency Δf which in turn is used to calculate of the speed of the organic reflectors in the blood flow.
2. Reliability and precision of blood vessel examination including blood pressure measurement based on ultrasound can be improved. For instance, the Doppler frequency spectra display the blood flow information from a certain area at a given depth, (control volume), and do not provide information about blood flow in other parts of the vessel which are visible on the ultrasound image. Therefore, in case choosing an inadequate control volume (ex., when cos α˜0) all diagnostic information will be incorrect.
3. References to non-specified devices and amplitude sensors (such as in U.S. Pat. No. 7,404,800B2) that produce the intracardiac pressure without further explanations.
Insufficient accuracy of results from hemodynamic measurements in blood vessels using certain Doppler methods are well documented. For example, in: S. B. Coffi, D. Th. Ubbink and D. A. Legemate. Non-invasive Techniques to Detect Subcritical Iliac Artery Stenosis. Eur. J. Vascular and Endovascular Surgery, 29, 2005; Ricardo Cesar, Rocha Moreira. Comparative study of Doppler ultrasonography with arteriography in the evaluation of aortic occlusive disease. Journal Vascular Brasileiro, 8, January/March 2009; or Vilhelm Schaberle. Ultrasonography in Vascular Diagnosis. A Therapy-Oriented Textbook and Atlas. Second Edition. Springer Heidelberg-Dordrecht-London-New-York, 2011.
The article Gernot Schulte-Altedorneburg, Dirk W. Droste, Szabolcs Felszegny, Monica Kellerman et al., Accuracy in vivo Carotid B-mode Ultrasound Compared with Pathological Analysis: Intima-Media Thickening, Lumen Diameter and Cross-Sectional Area. Stroke: Journal of the American Heart Association, 2001 demonstrates an insufficient accuracy of the results obtained for the examination of blood vessels using of the ultrasound B-mode imaging only.
Several patents are dedicated to using passive sensors placed in the human body and interacting with an external ultrasound source for analysis of physiological parameters of the human organism, as for instance U.S. Pat. Nos. 5,619,997 A, 5,989,190 A, 6,083,165 A, or US 20030176789 A1. However, these devices and methods have a number of drawbacks, namely the following:
1. The disclosures in patents U.S. Pat. Nos. 5,619,997 A, 5,989,190 A, 6,083,165 A consist in the suggestion that the physical parameters (pressure, temperature, viscosity) defining the state of the medium (including the human body) are determined as a functional relationship P=f(v), where P is the physical parameter and v is the frequency of the ultrasound wave reflected by a passive sensor placed in the medium which is different from the frequency of the primary ultrasound beam due the energy absorption by the sensor.
2. The disclosure in patent application US 20030176789 A1 suggests that the value of a specific physical parameter, such as the pressure, associated with the specific state of any medium (including the human body) is determined as the result of the frequency analysis of the acoustic signal reflected by the passive sensor implanted into the medium. The passive sensor has to be equipped with two parallel to each other reflective surfaces and the reflected signal is the result of the interference of the two acoustic signals: the first signal is reflected by the first reflective surface and second signal reflected by the second reflective surface.
The frequency analysis of the resultant signal permits allocate the frequencies of the maximal attenuation of the intensity and the value of the specific physical parameter is determined on the basis of the correlation relationships between the values of the parameters and the frequencies of the maximum attenuation of the resultant signal. The knowledge of the correlation between the values of the parameters and the frequencies is not sufficient to determine the functional relationship P=F(v). The method is dependent of the frequencies of both the direct and reflected signals, It is desired to provide a more simple method and system that is independent of the frequencies of both the direct and reflected signals which are also present in the following patent: US 20070208293 A1 “Methods and devices for non-invasive pressure measurement in ventricular shunts”. This disclosure relates to a ventricular shunt including a pressure-sensitive body that changes its dimensions in response to the pressure of the cerebrospinal fluid within the shunt.
The difference of US 20070208293 A1 from current document lies in several aspects. First, the flow of cerebrospinal fluid is quasi-stationary unlike the turbulent blood flow such as inside the heart chambers which are dealt with in the current disclosure. Second, the system from US 20070208293 A1 is tracking the distance changes between the transducer and ultrasonic beam reflecting gas-filled capsule, while in the current description the pressure is determined/estimated as the function of volumes of oscillating traceable regions in a series of images produced by medical imaging device placed fully outside of the body, regardless of presence or absence of any implanted devices. By an oscillating traceable region we mean a region appearing on most images of the series corresponding to the physiological domain where the pressure is measured or calculated, typically one or more of heart chambers, pulmonary artery and/or aorta.
On the other hand, we note the successful approach of the linear regression modeling of the maximal value of the Left Atrium pressure changes through the simultaneous measurements of the Left Atrium pressure with a catheter and trans-esophageal Doppler echocardiography published in the article “Noninvasive assessment of left atrial maximum dP/dt by a combination of transmitral and pulmonary venous flow”, see the Journal of the American College of Cardiology, V. 34, Issue 3, September 1999, P. 795-801, by Satoshi Nakatani, Mario J Garcia, Michael S Firstenberg, Leonardo Rodriguez, Richard A Grimm, Neil L Greenberg, Patrick M McCarthy. However, in this article it had not been reflected that not only Doppler echocardiography but a regular ultrasound or other imaging methods can be used to assess the atrial and more important ventricular (both left and right maximal dP/dt values called Left/Right Ventricular Pressure Rise) blood pressure and not only pressure changes, but absolute pressure values as well. This principle is realized in the present invention.
This present disclosure contains amongst others a novel method to calculate and determine said pressure and said method is independent of the frequencies of both the direct and reflected signals. Thus, prior technical solutions, such as disclosed in U.S. Pat. Nos. 5,619,997 A, 5,989,190 A, 6,083,165 A, or US 20030176789 are not analogues both in the methods of data collection and the methods of data processing of the current disclosure.
The approach in the present disclosure is based on the estimation of the pressure as a function of volumes of oscillating traceable regions (e.g. heart chambers) conducted via image processing of ultrasound (or other imaging device with similar functionality) recording.
Additionally, the present disclosure contains a provision for utilizing real-world data for increasing performance and accuracy obtained by calibration process, which contains initial synchronized simultaneous measurement recordings of the intra-cardiac blood pressure, such as with a micro-manometer catheter, and imaging device recordings, performed in case a patient undergoes a cardiac catheterization for any medical reason.
The essence of the current disclosure lies in the development of a direct non-invasive method of measurement of the blood pressure in the heart or a blood vessel and an apparatus for its practical implementation.
The present invention relies on the a usage of medical imaging devices capable to produce a time series of images displaying the boundaries, shape, size and position of inner physiological features such as heart chambers while being positioned fully outside of the body and communicating the said series of images in real time to a controlling device for subsequent processing.
The present invention is defined by the enclosed patent claims. The advantages of the disclosed method over the prior art presented by this disclosure include:
The method of the disclosure comprises a set of processes for pressure measurement based on the stream of images obtained in a non-invasive manner by an imaging device to estimate volumes of oscillating traceable regions in the stream of images.
A software comprising an algorithm for performing such pressure determination method is provided. Said software is preferably stored on a computer readable medium.
The present disclosure provides systems, methods, devices and software that permit to directly measure pressure and its dynamic changes inside a body from the outside of the body without the need of any implanted device.
The key novelties of the current disclosure are contained in the notions of the
For said Calculation or determination, the pressure P inside an oscillating traceable region in the body will be defined as the best fit function to the measured or estimated pressure values Pi≈P(ti, {Ti}i=1, . . . N) of a shape and position of the said oscillating traceable region.
In case of using T-Image {Ti}i=1, . . . N, the function is P(ti)=P(ti, {xj}j=1, . . . Mi⊂Ti), where xj are a set of coordinate parameters representing the said oscillating traceable region boundaries and position at each time corresponding to each frame Ti of the said T-image {Ti}i=1, . . . N.
In case of using Characteristic image {Ii}i=1, . . . N of the said T-image {Ti}i=1, . . N, a process which simplifies the model reducing its dimension and significantly improves calculation times without significant precision loss, Pi=P(ti, {xj}j=1, . . . Ki⊂Ii), where {xj}j=1, . . . K are a set of coordinate parameters representing the said oscillating traceable region size and position at each time corresponding to each column Ii of the said Characteristic Image {Ii}i=1, . . . N representing the said oscillating traceable region size and position at each time corresponding to each column Ii of the said Characteristic Image {Ii}i=1, . . . N.
The present disclosure contains a provision for utilizing real-world data for increasing performance and accuracy.
The real-world data is obtained by calibration process, which contains initial synchronized simultaneous measurement recordings of the intra-cardiac blood pressure with penetrating sensor, such as with a micro-manometer catheter, and imaging device recordings, performed in case a patient undergoes a cardiac catheterization for any medical reason independent of the usage of the present system and subsequent fitting of the parameters of the mathematical model to calculate the pressure function according to the measured, real-time absolute pressure values.
Through Calibration process, the directly measured intra-cardiac chamber pressures during catheterisation are aligned with synchronised imaging data.
Thus, when the system is calibrated, the (blood) pressure and its dynamic changes within the body, such as in a blood vessel can be calculated with high accuracy and stability anytime when a recording of the calibrated region is provided with the medical imaging device connected to the current system. The fitted mathematical models produced by the calibration process on various patients enables to produce generalized mathematical models to be applied to patients that have not undergone the calibration process but have similar physiological characteristics to those that were calibrated.
The present disclosure further provides an example of a system for subsequent calibration, measurements and calculations of the blood pressure based on the volume of cardiovascular structures including but not limited to the left atrium (LA), right atrium (RA), left ventricle (LV), right ventricle (RV), the pulmonary artery (PA) or the pulmonary artery wedge (PAW). During the calibration the pressure values Pi of the oscillating traceable regions at time moments ti are measures by direct pressure meters, such as catheter based blood pressure sensors connected to a pressure monitor unit. The imaging is provided simultaneously by a medical imaging device. Both intra body pressure meter measurement data and image stream {Ji}i=1, . . . N over time are synchronously recorded into the system and optimally regressed to a function P of a given shape in the way that Pi≈P(ti, {Ti}i=1, . . . N), where T-image {Ti}i=1, . . . N is defined as a chronological union of said initial image stream {Ji}i=1, . . . N with corresponding time stamps ti.
When the system is calibrated, the calculation is based on the utilization of the function P=P(ti, {Ti}i=1, . . . N) from previous calibration process: the non-invasive ultrasound measurement with an ultrasound apparatus is provided with further image processing derivation of the set of coordinate parameters {xj}j=1, . . . M representing the said oscillating traceable region size and position. The further substitution into the formula P(ti)=P(ti, {xj}j=1, . . . Mi⊂Ti) gives the real time pressure and pressure changes while the series of ultrasound images is recorded. In the absence of calibration for a particular patient machine-learning tools permit to estimate the pressure basing on calibration data from other patients with similar physiological parameters.
The above determined pressure values may provide valuable diagnostic information for potential therapeutical treatment of a patient, for example, based on RV (Right Ventricle) direct pressure measurement during calibration process, the method permits to assess non-invasively during the subsequent Ultrasound recordings the RVEDP—right ventricular end-diastolic pressure being the major marker of the right heart failure, cardiomyopathy, RV ischemia and infarction.
In the same way based on LV (Right Ventricle) or PAW (Pulmonary Artery Wedge) direct pressure measurement during calibration process, the method permits to assess non-invasively during the subsequent Ultrasound recordings the LVEDP—left ventricular end-diastolic pressure being the major marker of the left heart failure (CHF), myocardial infarction, tamponade, aortic regurgitation and others.
The achieved in this way real-time LVEDP/RVEDP ratio can be an independent marker for cardiac output response during Adaptive Servo-Ventilation therapy in Patients with heart failure.
The other real time characteristics which can be measured or estimated using the above method include but not limited to: Left Atrial Pressure (LAP), Right Atrial Pressure (RAP), Left Ventricular Pressure Rise dP/dtmax,L (LVPR), Right Ventricular Pressure Rise dP/dtmax,R (RVPR), Pulmonary Artery Pressure (PAP), Left Ventricular Systolic Pressure (LVSP), Right Ventricular Systolic Pressure (RVSP).
The below described embodiments with the references to the accompanying drawings present the features and advantages of the current invention. It has to be noted that being an example of a functional system the following implementation is not limited to mentioned devices/technologies that may be replaced by their similar modalities as long as the said modalities can produce the imaging data and maintain data connections to control units which, in turn, may be any computing devices restricted only by ability to run processing software and provide necessary data connections and user interfaces:
Specific embodiments or examples of the invention will now be described with reference to the accompanying drawings. This invention may, however, can be embodied in many different forms and should not be construed as limited to the embodiments demonstrated herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. The terminology used in the detailed description of the embodiments illustrated in the accompanying drawings is not intended to be limiting of the invention.
The present description of the current invention is given with reference to blood vessels or a heart chambers as an example only. It should be born in mind however that the present invention is not limited strictly to a blood vessels or heart chambers, but can be easily adapted to any medium transparent for ultrasound or other waves with the need to measure pressure changes of the liquid flow. Examples include the lymphatic system, bile ducts, urinary ducts, subarachnoid space around the brain and spinal cord (Cerebrospinal fluid), inside or exterior of the lung in the chest wall, etc. for measuring pressures and dynamic progress thereof.
Alternatively or in addition to ultrasound in order to generate series of images to be analysed for the intra body pressure determination, other systems capable of highlighting inner physiological features and streaming image data in real time, for instance Echo Doppler, Magnetic Resonance Imaging (MRI), or ionizing radiation based imaging systems like Roentgen (X-Ray, Computer tomographic Imaging [CT]) can be provided as medical imaging modalities for generating the input for the pressure determination.
Additionally, while the present description refers to the usage of 2-dimensional cross-section ultrasound imaging of the investigated chamber as is produced by contemporary sensors, is not limited to it and can be utilized with different modalities that produce several 2-dimensional cross-sections or a full 3-dimensional representation of the investigated chamber.
In accordance with preferred embodiments a system comprises for example:
1) For the Calibration Process (
2) For the General (or post-calibration) Usage Process (
3) Optionally the system includes a remote cloud or other specialized server (110, 206, 302, and 402), operation of which permits both calibration control unit (106) and end-user control unit (203) to store, retrieve and exchange data if internet connection is available, but it is generally possible to transfer of the data by other means, directly between the devices or by physical medium.
4) During the Calibration Process, the software, positioned either on the Calibration control unit (106) or on remote cloud or other specialized server (110) processes the recorded data by using the algorithm described in items (7)-(8) and creates and stores a calculation model (303) for calculation of subsequent pressure results from medical imaging device recordings of the previously calibrated patient. This model is transferred directly or via the server to end-user control unit.
5) During the General (or post-calibration) Usage Process (
6) In absence of previous calibration model for the specific patient (
7) The data recorded during the Calibration Procedure is processed as follows:
8) Additionally to the method described above in item (7) a simplified method of processing may be used which comprises of:
This method enables to greatly increase the speed of processing and reduces the computational power requirements while maintaining enough accuracy given the images are recorded from a similar angle to the calibration.
9) During General (or post-calibration) Usage, the patient
10) Highlighting a diagnostic example, the system is capable of assessment and calculation of LVEDP (Left-Ventricular End-Diastolic Pressure) (
11) The other real time characteristics which can be measured or estimated using the above method include but not limited to: Left Atrial Pressure (LAP), Right Atrial Pressure (RAP), Left Ventricular Pressure Rise dP/dtmax,L (LVPR), Right Ventricular Pressure Rise dP/dtmax,R (RVPR), Pulmonary Artery Pressure (PAP), Pulmonary Capillary Wedge Pressure (PCWP), Left Ventricular Systolic Pressure (LVSP), Right Ventricular Systolic Pressure (RVSP).
12) The system includes software with at least the following capabilities:
The present invention has been described using a non-limiting detailed description of various embodiments and examples thereof. It should be appreciated that the present invention is not limited by the above-described examples and that one ordinarily skilled in the art can make changes and modifications without deviation from the scope of the invention as will be defined below in the appended claims.
Below are listed some of the modifications, which are within the scope of invention as defined by the appended claims:
It should also be appreciated that features disclosed in the foregoing description, and/or in the foregoing drawings and/or following claims both separately and in any combination thereof, be material for realizing the present invention in diverse forms thereof. When used in the following claims, the terms “comprise”, “include”, “have” and their conjugates mean, “including but not limited to”.
The present invention has been described above with reference to specific examples. However, other embodiments than the above described are equally possible within the scope of the invention. Different method steps than those described above, performing the method by hardware or software, may be provided within the scope of the invention. The different features and steps of the invention may be combined in other combinations than those described. The scope of the invention is only limited by the appended patent claims.
