Patent Application
20220369941
Peripheral Artery Disease (PAD) is a condition where atherosclerosis of the big arteries or other obstructive diseases affecting the small arteries compromise the ability of the circulatory system to deliver sufficient blood to peripheral regions of the body. The worldwide number of prevalent cases of PAD exceeds 200 million and the number of incident cases is over 10 million, with two thirds of prevalent cases of PAD being asymptomatic.
PAD is associated with significant morbidity and mortality. The compromised circulation may lead to chronic limb threatening ischemia (CLTI), a condition characterized by pain at rest, ulcers and wounds which do not heal. CLTI may lead to infection, tissue loss, and subsequent amputation. In addition, elevated prevalence of coronary artery disease, stroke, and hypertension are associated with PAD.
Vascular procedures and other treatments exist which can often improve the condition of PAD patients. However, the asymptomatic nature of the disease often means that treatment may not occur until after a patient develops CLTI and is at risk of amputation.
Many diagnostics for PAD have been proposed or are under development. None have advanced to the stage where they have significantly increased the detection of obstructive disease affecting big and small arteries, i.e., detecting the real tissue perfusion. Thus there is a need for non-invasive, inexpensive and quick diagnostics for PAD with a high degree of sensitivity and specificity in detecting tissue perfusion in order to identify PAD in its earliest stages, to evaluate the effectiveness of revascularization procedures, and to monitor the progression of the patient's disease.
Moreover, even when PAD is diagnosed, only time-consuming or expensive invasive diagnostics are currently available to identify and quantify the regions (e.g., angiosomes) with circulatory insufficiency. And even those diagnostics do not always highlight the locations most appropriate for treatment. For example, angiography produces a detailed map of the fluid in the arteries, but may not accurately reflect the flow passing through small collateral vessels connecting different angiosomes.
Thus, for invasive procedures, the physician must find the locations to treat by experienced guesswork, which may either prolong the procedure, if it takes time to find the best locations to treat, or leave some patients no better off, if those locations cannot be located. There exists the need for non-invasive, inexpensive diagnostics which can quickly and quantitatively highlight the circulatory health at locations a clinician examines in order to better plan and effect treatment of PAD.
Besides PAD patients, there are other medical needs which would be addressed by a non-invasive, inexpensive diagnostic which measures circulatory health at specific locations. For example, patients undergoing plastic or reconstructive surgery may have their vascular structures affected by the surgery, whether such structures are intentionally revised as part of the surgery or whether there is a risk that surgical intervention could compromise the health of vascular structures near the surgical field. There exists the need for a diagnostic to give quick, non-invasive feedback to the surgeon as to whether the circulation at locations in question are healthy after the surgical intervention.
Patients without PAD presenting systemic disease affecting connective tissue (e.g., scleroderma, rheumatoid arthritis, lupus erythematosus, etc.), or oedema, or cardiovascular conditions reducing cardiac output (e.g., heart failure, hypovolemia, septic shock, etc.) can present reduced tissue perfusion. Also in these cases there exists the need for a diagnostic to give quick, non-invasive feedback to the physician as to whether these conditions can affect the circulation at locations in question.
One aspect of the invention is directed to a handheld probe that the operator may press against the patient. The probe has two parts which can move relative each other. The first part, which presses against the patient, has a blood circulation sensor near the tip contacting the patient which measures some aspect of the patient's circulation, e.g., the blood volume (i.e., the quantity of blood in the tissue region being sensed), the blood flow (i.e., the rate of flow of blood in the tissue region being sensed), or a pulsatile signal (i.e., the change in blood volume, or the change in blood flow, or the change in blood pressure, etc. in the tissue region being sensed). The operator holds a second part of the probe which is further away from the patient. The probe contains a means by which the second part transmits a force to the first part which is opposed by the patient, and a force or pressure sensor which provides a means of measuring the force exerted. The first part has a substructure with some defined shape whereby the force applies pressure to the patient. The probe further contains a means by which it can measure some aspect of the patient's circulation as a function of the applied pressure (e.g., an electronic controller connected to the circulation sensor and to the force or pressure sensor, with the electronic controller being configured to report the measured results to an observer and preferably also a data storage unit).
In one embodiment, the probe consists of a pair of telescoping cylindrical structures where the cylindrical structures are connected by a compression spring. The cylindrical structure contacting the patient has an atraumatic tip which contains a photoplethysmographic (PPG) sensor at the tip for sensing blood circulation. The operator holds the other cylindrical structure, which has a force or pressure sensor, and is able to apply pressure to the patient transmitted by the cylinders. The probe contains electronics which calculates the pulsatile signal from the PPG sensor while measuring the applied force via the force or pressure sensor. The pressure at which the pulsatile signal disappears or is significantly altered indicates the Tissue Perfusion Pressure (TPP) which is a significant marker of the circulatory health at the location where the probe contacts the patient. The absence of a pulsatile signal without any pressure being applied is a significant marker of extremely severe circulatory failure.
In another embodiment, the probe consists of two portions, with one portion carrying a blood circulation sensor (e.g., a PPG sensor) at its tip and with the other portion being configured to be held by the user so that the user can use the grasped portion to press the blood circulation sensor portion against a patient. A force or pressure sensor (e.g., a strain gauge) is provided on the probe to measure the force or pressure applied to the blood circulation sensor portion by the grasped portion.
In one form of the invention, there is provided an apparatus for performing a diagnostic measurement of blood circulation, wherein the apparatus comprises:
In one form of the invention, the force or pressure can be varied gradually so that a sufficiently precise TPP can be measured.
In another form of the invention, there is provided a method for performing a diagnostic measurement of blood circulation, wherein the method comprises:
In one form of the invention, the force or pressure is varied gradually so that a sufficiently precise TPP can be measured.
These and other objects and features of the present invention will be more fully disclosed or rendered obvious by the following detailed description of the preferred embodiments of the invention, which is to be considered together with the accompanying drawings wherein:
A variety of sensors have been used to assess the health of a patient's blood circulation. One of the most common is the finger pulse oximeter, which measures optical transmission at two wavelengths and its periodic variation with the patient's pulse, to measure the oxygen saturation of blood flowing to a patient's fingertip. Ultrasound is also used to measure blood flow, with Doppler ultrasound measuring blood velocity. X-ray imaging combined with contrast agents injected into a patient's arteries produces angiograms with highly resolved images of the fluid in the arteries.
Transcutaneous pO2 sensors can sense oxygenation through the skin after heating the skin to allow oxygen to permeate the skin. Skin perfusion pressure (SPP) sensors measure the effect of pressure on blood circulation using one of three different sensing techniques for SPP measurement, i.e., radioisotope clearance, PPG or laser Doppler. Hyperspectral imagers in combination with image processing can image blood vessels and the degree of blood oxygen saturation. Laser speckle single pixel or image sensors are another means of measuring blood flow.
Another sensing methodology measures the ankle brachial index (ABI) by taking the ratio of systolic blood pressure at the ankle to that at the arm, which gives an assessment of blood circulation at the foot. Toe pressure and toe brachial index are considered more accurate, because this measurement gives an assessment of blood circulation in the extreme peripheral tissues.
While all of these sensors and methodologies provide useful information, they generally fall short in providing enough information to diagnose when a patient has PAD. While a measure using the ABI is correlated with PAD, it is not very sensitive or specific in predicting whether a patient has PAD, especially in patients with CLTI. ABI detects obstruction in the big arteries above-the-ankle, but is unable to detect small artery disease below-the-ankle. Toe pressure can be evaluated only in the first toe (i.e., the so-called “big toe”), but it cannot be applied in other sites of the foot or the body. In other cases, the various methodologies may measure a single quantity accurately, over a limited portion of the patient's tissue, but that may not be sufficient to diagnose PAD or to localize it to a specific blood vessel which can be targeted for surgical intervention to improve blood circulation.
For example, angiography provides detailed maps of the circulatory system that allow measurement of the physical size of blood vessels large enough to be imaged distinctly. However, such images may not predict the sufficiency of blood flow due to the inability to map small collateral vessels which feed various angiosomes. Several of the techniques only provide reliable measures of blood circulation near the skin, but subdermal tissues may experience different perfusion. The body's skin is subjected to the thermoregulatory function, and every measurement of its perfusion requires a preliminary time for the patient to adapt to the ambient temperature. Many of the techniques do not enable the measurement to be taken in volumes small enough or in arbitrary positions on the patient in order to localize circulatory problems to specific blood vessels or angiosomes.
Moreover, many of these techniques require the application of sensors and a pressure cuff on the skin of the patient (e.g., the SPP, PPG, ABI, and toe pressure techniques), leading to the need for resterilization of the device before using it on another patient.
Thus there exists a need for a device which can assess blood circulation within subdermal tissues that is not affected by, or is only partially affected by, thermoregulation, and which can probe a relatively small volume of tissue in an arbitrary position on the patient in order to diagnose PAD and localize circulatory problems to specific blood vessels or angiosomes. The device is a handheld probe (or fixture mounted probe) that can easily be covered with a sterile, disposable cover, avoiding the risk of infection transmission and the time for resterilization.
A device which overcomes these limitations is pictured in
In one preferred form of the invention, and looking now at
As shown in
As the applied pressure increases, the blood is squeezed out of the vessels. Initially, the low pressure vessels (venous and capillary) are emptied of blood. With increasing pressure, the pulsatile flow of the arterial and arteriolar vessels is progressively overwhelmed. When the tissue pressure reaches the maximum pulsatile pressure of arteries and arterioles, the pulsatile signal disappears. Due to the pressure gradient, not every portion of the scanned tissue sample experiences the same pressure and hence there may not be a distinct pressure where the pulsatile signal disappears.
Nevertheless, a measure of how the blood circulation changes with applied pressure may be constructed that indicates the health of the patient's circulation. For instance, at high enough applied pressure, blood circulation measured by the blood circulation sensor 20 will fall below a defined threshold value. This threshold occurs at lower pressure for patients with PAD. This threshold pressure is termed the TPP. The TPP is greater for individuals with healthy circulation and less for individuals with PAD. In case of severe PAD, the pulsatile signal can be absent in the tissue circulation, and TPP is zero. In case of healthy subjects, in some areas of the body the pulsatile signal cannot be set to zero by any applied pressure, because blood continues to flow in bones and other non-compressible areas. The same phenomenon is noted with ABI, where the threshold of a healthy ABI is one where the ankle pressure is >0.9 times the arm pressure and lower indices are correlated with PAD. This effect of lower TPP for patients with PAD is illustrated in
The observation that the pressure at which a measure of circulation falls below a threshold provides information about PAD is not new, nor is the concept of measuring said pressure. However, previous devices in the literature use a pressure cuff that surrounds a limb to apply pressure, and many are only capable of measuring that pressure at the skin, not in deeper tissue. The new probe of the present invention differs in that the pressure is applied locally. Thus it may provide more detailed information about the patient's blood circulation at a particular position on the body. As is pictured in
The variation of blood circulation with applied pressure measured by the probe may be observed differently depending on the particular sensors used and the configuration of the probe. In one embodiment, both the blood circulation sensor 20 and the force or pressure sensor 25 may provide output that is mechanically linked to the two sensors 20, 25 (e.g., the two sensors 20, 25 may be mechanical in nature). For example, and looking now at
In other configurations, and more preferably, both the blood circulation sensor 20 and force or pressure sensor 25 may be electronic and their output may be mediated by electronic circuitry, e.g., a controller, and output as a visual or auditory signal. For instance, consider the sensor pictured in
The time-sampled signal may be analyzed by a microprocessor or other computer to measure the circulation. A simple measure is the peak-to-valley modulation of the AC signal, either the absolute value or the fractional value as a ratio to the time-averaged or DC value of the signal. The force or pressure sensor 25 may also be digitized with an ADC. If the applied force/pressure is varied slowly enough, i.e., on a timescale measured in seconds, the measure of circulation may be assessed as a function of the applied force/pressure. The pressure at which the measure of circulation falls below an appropriate threshold then becomes the TPP for that location on the patient. That threshold may be a fixed threshold, either of the absolute or fractional value of a particular measure. It may also be a proportional threshold of an initial value. Consider a PPG signal, as shown in
Other measures of the blood circulation may be used in order to define the TPP. The integral of the sensor signal over a fixed time period or over some number of heartbeats, or the integral of the sensor signal above a fixed or proportional threshold, may be used. In addition, a measure of the shape of the curve may be used. In
Since there will be pressure gradients within the tissue from application of pressure by the probe, and the circulation sensor measures over a volume of tissue, the measured blood circulation may not exhibit a very sharp cutoff with increasing pressure. Rather, it is likely to decrease more gradually. Thus some clinical data may be required to establish a measure of circulation and an appropriate threshold for a TPP that exhibits a high degree of sensitivity and specificity for diagnosing PAD or identifying blood vessels most affected by the disease.
The probe may be configured to produce an electronic output that signifies the sensor measurements or derived quantities. For instance, a speaker may output a tone whose pitch or volume is correlated with the output, or a display may show either a digital number or some other visual signal, e.g., color or intensity of an LED or lamp reflecting the output. The outputs may also be sent electronically, either by wired or wireless connection, to a computing device which has a user interface (UI) that displays the measurements. The computing device may be a computer, tablet, or smartphone. When a derived quantity, such as the peak-to-valley modulation measurement, must be calculated from the data, that calculation may either be done by an embedded processor in the device or by a separate computing device.
For embodiments where the force or pressure does not result in a mechanical indication, the probe may employ an electronic transducer that senses either the applied force or pressure. The output of that transducer (i.e., the output of force or pressure sensor 25) can then be reported on a computer or smaller device display. For instance, a strain gauge is a sensor whose output typically reflects the strain on a thin foil which can be related to the applied force. Similarly, force sensitive resistors produce an output related to the applied force. In both of these cases, the tip of the probe must be rigidly linked to the sensor. See, for example,
Another type of sensor is a pressure sensor which typically senses the deformation of a membrane by a pressure transmitted by a fluid, either liquid or gas, which is in contact with the membrane. This embodiment generally requires the tip of the probe push a piston in a cylinder whose contents come under pressure. See, for example,
Alternatively, and as seen in
One embodiment senses the displacement of the sliding contact on a potentiometer by measuring the varying resistance to that contact.
Another embodiment uses a syringe for a similar purpose.
Some calculation may be required to equate the measured force or pressure to the pressure applied by the probe. This is a result of two factors. First, the applied pressure will depend on the area over which the probe contacts the patient and can apply a force to the skin. Second, it will depend on the properties of the materials used in the probe, especially at the tip. It is desirable that applying the probe to the patient causes no trauma, especially since patients suspected of having PAD may have wounds which do not heal quickly or at all due to circulatory insufficiency. Thus the materials chosen may be soft and compliant. While metals and hard plastics will undergo little deformation, the deformation of more compliant materials like rubber must be taken into account when calculating the pressure applied to the patient.
Additional factors may be required to calculate the pressure applied to the patient. For embodiments where force is measured, that force must be divided by the effective area of the tip of the probe. For embodiments where pressure is measured using a sliding piston-like member such as the probe piston 85 shown in
Additionally, the measurements made should account for the pressure gradients which will be produced in the patient's tissue. As shown in
It is notable that the devices pictured in the Figures may employ a variety of blood circulation sensors 20. Sensors that can probe deep into the patient's tissue are preferred. However, measuring the TPP for mainly the dermal layer with a localized device may also provide useful information that is not available from other devices. Thus the blood circulation sensor 20 at the tip of the probe may be chosen from the range of sensors including ultrasound, laser Doppler, tcpO2, SPP, PPG, hyperspectral imagers, and laser speckle.
Depending on the location on the patient, it may be preferable to have a tip of a specific size and shape and made of a particular material. For some locations on the body, a tip with a flattened shape may be more suitable while for others, a rounded tip of a specified radius may be advantageous. For example, when probing around the hand or wrist or the bones of the foot, a probe with a smaller tip may afford greater precision in measuring the TPP. For areas where the underlying tissue is more uniform over several centimeters of lateral extent, a tip with a large flat region may be preferred.
It is possible to engineer the probe so such tips with the appropriate shape and size may be installed by the device operator just prior to measuring a particular location on a patient. For example, the PPG sensor shown in
This invention was conceived as a means by which an operator, e.g., a physician, would manually place the probe against a patient and manually vary the pressure applied to the patient. However, the role of the operator may be replaced by a fixture which holds the tip against the patient and by an automated mechanism in the probe which applies a force or pressure which is transmitted to the patient. The fixture may be a rigid mechanical structure attached to the furniture the patient rests upon or it may be straps or tape attaching the probe to the patient or the furniture.
Many mechanisms can be constructed which would apply the force or pressure. Mechanisms which are considered linear actuators could be mounted to the probe and exert a force on the fixture, thereby causing an opposing force to be transmitted to the patient. A linear actuator consisting of a motor turning a screw held by a nut would exert a force against the nut, with the force increasing or decreasing depending on the direction the screw is turned. Current going through a coil of wire exerts a force on a magnetic material passing through the inside of the coil proportional to the current and resulting magnetic field. Other mechanisms like an inflatable bladder apply pressure when they are constrained by a housing and the pressure exerted on the housing varies with the inflation pressure. Additional mechanisms known to those skilled in the art could be automated to apply a variable force or pressure of the sort required to measure the TPP.
See, for example,
It will be appreciated that a fixtured, automated probe of the sort described need not be as large as one designed to be hand-held. A compact design could produce a probe that would not interfere with the actions of a surgeon who wanted to monitor the TPP at one or more locations during a procedure.
It should also be appreciated that probe 5 may be mounted to, or be formed as part of, a robotic arm, so that probe 5 can be manipulated robotically. In this case, blood circulation sensor 20 and force or pressure sensor 25 are preferably electrical, and their outputs are preferably transmitted along the length of the robotic arm to a controller 30 located proximal to the robotic arm.
The results from two different prototype devices demonstrate the utility of this approach. Measurements taken with the device shown in
The device shown in
It is clear from these measurements that the measured TPP as defined above and as measured at various locations with embodiments described herein shows a clear difference between healthy patients and those diagnosed with PAD. It also shows that patients who undergo a revascularization procedure show improved circulation as measured by the TPP.
The TPP is much higher for healthy patients than for PAD patients who have undergone a revascularization procedure. It is notable that for PAD patients, no pulsatile signal was measurable with the subject apparatus at some locations even with no pressure applied to the patient so the TPP at these locations was measured to be 0.
Other embodiments of this invention may be more sensitive and able to detect the pulsatile signal on these patients. This highlights the fact that measurements of TPP are likely to be device and location dependent. As is seen in
Although limited, the measured data show significant differences in the improvement from revascularization to different patients and significant variation at different locations. This is expected since multiple arteries supply the foot, and a revascularization procedure will not affect all arteries equally. This highlights the value of information TPP measurement with a device that can probe different locations can provide. TPP measurement can be used by a surgeon to identify locations or angiosomes with poor circulation which could benefit from intervention. It can also be used to quantify the improvement resulting from a surgical intervention. If this measurement can be made in real time during a surgical procedure, it offers the possibility of significantly improving surgical interventions. TPP measurement is non-invasive and is much less costly than the gold standard for assessing circulatory improvement during a procedure, i.e., x-ray angiography with contrast dyes.
Although various exemplary embodiments of the invention have been disclosed, it should be apparent to those skilled in the art that various changes and modifications can be made which will achieve some of the advantages of the invention without departing from the true scope of the invention.
This patent application claims benefit of pending prior U.S. Provisional Patent Application Ser. No. 63/169,456, filed Apr. 1, 1921 by VOTIS Subdermal Imaging Systems, Ltd. and Roberto Ferraresi for COMPACT DEVICE FOR SENSING CIRCULATORY HEALTH (Attorney's Docket No. VOTIS-1 PROV), which patent application is hereby incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 63169456 | Apr 2021 | US |
