WO2016125087A1

WO2016125087A1 - Deep vein thrombosis prevention

Info

Publication number: WO2016125087A1
Application number: PCT/IB2016/050543
Authority: WO
Inventors: Alex TENDLER; Tomer Yablonka; Alon Ironi; Amnon Harpak; Ronen Jashek; Avner Taieb
Original assignee: Siano Mobile Silicon Ltd.
Priority date: 2015-02-04
Filing date: 2016-02-03
Publication date: 2016-08-11

Abstract

Systems and methods are described, including a system (20) that includes a control unit (34), a plurality of electrodes (30a, 30b, 32a, 32b) connected to the control unit, and a mobile device (22). The mobile device comprises a processor (24) configured to, when the electrodes are coupled to skin of a subject, wirelessly communicate a control signal to the control unit that causes the control unit to compute a measure of flow of blood into a portion of a body of the subject during a period of time, based on impedance measurements acquired, using at least some of the electrodes, during the period of time, and, in response to the computed measure, control at least some of the electrodes. Other embodiments are also described.

Description

DEEP VEIN THROMBOSIS PREVENTION

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the priority of commonly-assigned US Provisional Application 62/1 1 1,705, filed February 4, 2015, whose disclosure is incorporated herein by reference.

FIELD OF THE IN VENTION

Embodiments of the present invention relate to the measurement of blood flow, and additionally relate to electrostimulation, such as transcutaneous electrostimulation.

BACKGROUND

Deep vein thrombosis (DVT) is the formation of a blood clot (thrombus) within a deep vein, such as a deep vein in a leg. DVT is associated with potentially life-threatening complications, such as postthrombotic syndrome and pulmonary embolism.

US Patent 8,755,894 to Nachum, whose disclosure is incorporated herein by reference, describes a non-invasive method comprising positioning a first electrode on a lower end of a lower leg, a second electrode on the lower leg, and a third electrode on an upper end of the lower leg, whereby the first and third electrodes are disposed on opposite ends of the lower leg, and the second electrode and one of the first and third electrodes are disposed on a same end of the lower leg; effecting a sequence of muscuiar contractions of the lower leg by (i) applying a first electrical impulse between the electrodes on the same end of the lower leg to induce a first muscular contraction and (ii) applying at least a second electrical impulse between the first and third electrodes to induce a longitudinal muscular contraction; and repeating operations (i) and (ii), to repeatedly induce the contractions, to effect the increased flow of blood.

US Patent 3,340,867 to Kubicek, whose disclosure is incorporated herein by reference, relates to plethysmography and particularly to an impedance plethysmograph and process of using the same.

Nyboer, Jan, Marian M. Kreider, and Leonard Hannapel. "Electrical Impedance Plethysmography A Physical and Physiologic Approach to Peripheral Vascular Study," Circulation 2.6 (1950): 81 1 -821, which is incorporated herein by reference, describes a method for deriving the volume of a pulse. Bernstein, Donald P. "Impedance cardiography: Pulsatile blood flow and the biophysical and electrodynamic basis for the stroke volume equations, " Journal of Electrical Bioimpedance 1.1 (2010): 2- 17, describes aspects of impedance cardiography (ICG).

SUMMARY OF TH E INVENTION

There is provided, in accordance with some embodiments of the present invention, a system that includes a control unit, a plurality of electrodes connected to the control unit, and a mobile device that includes a processor. The processor is configured to, when the electrodes are coupl ed to skin of a subject, wirei essly communicate a control signal to the control unit that causes the control unit to (i) compute a measure of flow of blood into a portion of a body of the subject during a period of time, based on impedance measurements acquired, using at least some of the electrodes, during the period of time, and (ii) in response to the computed measure, control at least some of the electrodes.

in some embodiments,

the impedance measurements include a time-varying impedance Z between two of the electrodes over at least one systolic period of a cardiac cycle, and

the controi unit is configured to compute the measure by:

performing an adjusted backward extrapolation from an end of the systolic period, and

using the adjusted backward extrapolation, computing a volume of blood flow

2 2

that is less than (pL /Zo )^x(min(-dZ/dt)xT + Zp - Zf), where p is 150 Ω-cm, L is a distance between the two electrodes, dZ/dt is a derivative of Z with respect to time, min(-dZ/dt) is a minimum of -dZ/dt over the systoli c period, T is a total duration of the systolic period, ZF is a value of Z at the end of the systolic peri od, Zi is a value of Z at a beginning of the systolic period, and Zo is a mean of Z\ and a value of Z at an end of the cardiac cycle. in some embodiments, the control unit i s configured to compute the volume by computing (pL 7Zo ^')x(-dZ/dt|i8^xT + ZF - Zi), where -dZ/dtjt8 is a value of -dZ/dt at a time t.8 during the systolic period that is different from a time during the systolic period at which -dZ/dt = min(-dZ/dt).

In some embodiments, t8 = 2t3 - 12, where t2 is a time during the systolic period at which

-dZ/dt reaches a maximum, and t3 is a time during the systolic period at which Z reaches a minimum.

in some embodiments, the control unit i s configured to, in response to the computed measure being less than a threshold, cause the electrodes to increase electrostimulation of the subject.

In some embodiments, the processor is further configured to:

receive, from the control unit, the computed measure, and

in response to the computed measure, prompt the subject to adjust a location of at least one of the electrodes.

In some embodiments, the control unit is configured to obtain electromyographic measurements of the subject from at least some of the electrodes, and to control at least some of the electrodes in response to the electromyographic measurements.

In some embodiments, the control unit is configured to:

obtain a respective one of the electromyographic measurements at each of a plurality of different values of an electrostimulation parameter,

identify a threshold one of the values, by ascertaining that a signal energy of the electromyographic measurements does not increase as the value of the parameter is increased beyond the threshold, and

control the at least some of the eiectrodes in response to the electromyographic measurements, by setting the parameter of the electrostimulation to be less than the threshold.

There is further provided, in accordance with some embodiments of the present invention, a method for electrostimulation. Using a mobile device, a control signal is wirelesslv communicated to a control unit, the control unit being connected to a plurality of electrodes coupled to skin of a subject. Using the control unit, in response to the control signal, (i) a measure of flow of blood into a portion of a body of the subject during a period of time is computed, based on impedance measurements acquired, using at least some of the electrodes, during the period of time, and (ii) in response to the computed measure, at least some of the electrodes are control led.

In some embodiments, the portion of the body of the subject includes a leg of the subject.

There is further provided, in accordance with some embodiments of the present invention, a computer software product including a tangible non-transitory computer-readable medium in which program instructions are stored. The instructions, when read by a processor of a mobile device, cause the processor to wirelesslv communicate a control signal to a control unit that is connected to a plurality of electrodes coupled to skin of a subject. The control signal causes the control unit to (i) compute a measure of flow of blood into a portion of a body of the subject during a period of time, based on impedance measurements acquired, using at least some of the electrodes, during the period of time, and (ii) in response to the computed measure, control at least some of the electrodes.

The present invention will be more fully understood from the following detailed description of embodiments thereof, taken together with the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a schematic illustration of a system for electrostimulating a subject, in accordance with some embodiments of the present invention; and

Fig. 2 shows plots of example plethysmographic data, whi ch may be acquired and used in accordance with some embodiments of the present invention.

DETAILED DESCRIPTION OF EMBODIMENTS

OVERVIEW

In embodiments of the present invention, electrostimulation (typically, transcutaneous electrostimulation) is used to improve blood circulation, and thus, help prevent an occurrence of DVT. For example, an apparatus comprising a control unit and a plurality of electrodes, coupled to a subject's leg, may be used to drive stimulating electric currents into the leg. The stimulating currents cause muscles of the leg to contract, thus causing an increase in blood flow through the leg, primarily by increasing venous return.

Typically, impedance plethysmography is used to monitor the flow of blood. In particular, the impedance between a pair of the electrodes is measured over a period of time, and, based on the measured impedance, the control unit computes a measure of the fl ow of blood into the portion of the body of the subject that is between the electrodes, during the period of time. For example, the control unit may compute the average flow rate of the blood into the portion of the subject's body during the period of time. The control unit then compares this measure to a threshold. If the measure is below the threshold, the control unit increases electrostimulation of the subject, e.g., by commencing an electrostimulation program, or by adjusting a parameter of a currently-running electrostimulation program. Typically, the control unit performs the various tasks described herein in response to receiving control signals from a mobile device, such as a smartphone. An advantage of using plethysmography to control the treatment of the subject is that the treatment is generally provided only when needed, and with minimal excess power consumption.

Embodiments of the present invention further provide an adjusted backward extrapolation method for estimating, based on the impedance measurements, the volume of blood flow during each systolic period during the period of time. This method has been found to be more accurate than any other method that has heretofore been described.

SYSTEM DESCRIPTION

Reference is initially made to Fig. 1 , which is a schematic illustration of a system 20 for electrostimuiating a subj ect, in accordance with some embodiments of the present invention.

System 20 comprises a cuff (or "sleeve") 26, which may be worn around a limb of the subject's body. For example, cuff 26 may be worn around the lower leg 28 of a subject, as shown. (Fig. 1 shows both a front view and back view of the leg.) Cuff 26 comprises a plurality of stimulating electrodes. When the cuff is worn around the leg, the stimulating electrodes are coupled to the skin of the leg, and thus, may electrostimulate the leg, as further described below. For example, an electric current ma be passed between two stimulating electrodes 30a and 30b, disposed, respectively, near opposite ends of the cuff. When the electrodes are positioned over the calf of the leg, as shown, such a current may cause contraction of the gastrocnemius, soleus, tibialis anterior, and/or tibialis posterior muscles, and/or stimulation of the peroneal nerve, which causes the leg muscles to contract in a manner that mimics walking.

In the context of the present application, including the claims, electrodes may be considered to be "coupled" to skin even if they are not in direct contact with the skin, as long as no layer of air separates the electrodes from the skin. For example, even if, as is typically the case, the electrodes are embedded between the inner and outer layers of the cuff, the electrodes may nonetheless be coupled to the leg via the inner layer of the cuff.

Cuff 26 further comprises two sensing electrodes 32a and 32b, which, as further described below, are used to acquire plethysmography measurements. In some embodiments, the cuff further comprises another set of sensing electrodes (not shown), used to acquire electromyographic measurements. Alternatively, sensing electrodes 32a and 32b may acquire electromyographic measurements, in addition to the plethysmography measurements. In some embodiments, a single pair of electrodes performs the functions of both the stimulating electrodes and the sensing electrodes.

The cuff further comprises a control unit 34, which comprises circuitry configured to receive feedback from the electrodes, perform relevant computations based on the feedback, control the electrodes, exchange communication (e.g., wirelessly) with other devices, and/or perform any other relevant tasks. For example, control unit 34 typically comprises a processor 35, comprising a central processing unit (CPU) configured to execute program instructi ons (provided, for example, in microcode) that cause processor 35 to carry out the various tasks described herein. Control unit 34 typically further comprises a wireless transceiver (not shown), such as a Bluetooth Low Energy (BLE) transceiver. Typically, the circuitry of control unit 34 is fabricated on a printed circuit board (PCB), e.g., in a system -on-chip (SoC). Typically, the stimulating electrodes and sensing electrodes are wiredly connected to control unit 34, e.g., as shown in the figure. (Alternatively, at least one of the electrodes may be wirelessly connected to the control unit.)

Typically, the cuff further comprises a power source (not shown), comprising, for example, one or more batteries.

It is noted that the particular configuration of cuff 26 shown in Fig. 1 is only one of many possible configurations. For example, the numbers and/or placement of the electrodes on the cuff may be different from that which is shown. Moreover, is some embodiments, the sensing electrodes and/or stimulation electrodes may be coupled to the skin via a wrap, adhesive patch, sock, or other supporting device, instead of via a cuff. The electrodes may be coupled to the supporting device in any suitable manner, including, for example, printing or weaving. Alternatively, the electrodes may be coupled directly to the skin, without any supporting device at all.

Typically, system 20 further comprises a mobile device 22, such as a smartphone, which is configured to communicate wirelessly with control unit 34, e.g., using the Bluetooth Low Energy (BLE) protocol. A software application running on device 22 includes program instructions that cause a processor 24 of device 22 to receive input from the subject, the control unit, and/or other sources (e.g., the Internet, or a physician 38 of the subject), process the input, and, in response to processing the input, communicate relevant instructions to the control unit. For example, as further described below, processor 24 may communicate, to the control unit, a control signal that causes the control unit to compute a measure of blood fl ow and, in response to the measure, increase or decrease electrostimulation of the subject.

In general, each of processor 24 and processor 35 may be embodied as a single processor, or a cooperatively networked or clustered set of processors. Processor 24 and/or processor 35 is typically a programmed digital computing device comprising a central processing unit (CPU), random access memory (RAM), non-volatile secondary storage, such as a hard drive or CD ROM drive, network interfaces, and/or peripheral devices. Program code, including software programs and/or microcode, and/or data, are loaded into the RAM for execution and processing by the CPU and results are generated for disp!ay, output, transmittal, or storage, as is known in the art. The program code and/or data may be downloaded to the processor in electronic form, over a network, for example, or it may, alternatively or additionally, be provided and/or stored on non-transitory tangible media, such as magnetic, optical, or electronic memory. Such program code and/or data, when provided to the processor, produce a machine or speci al- purpose computer, configured to perform the tasks described herein.

Reference is now made to Fig. 2, which shows plots of example plethysmographic data, which may be acquired and used in accordance with some embodiments of the present invention. Fig. 2 includes a first plot 21, which shows a time-varying impedance (Z) between the sensing electrodes. Plot 21 is based on actual impedance measurements that were acquired, by the inventors, over several cardiac cycles. Since, for noise removal, the acquired measurements were averaged over the cardiac cycles, the horizontal time axis of plot 21 shows only a single cardiac cycle, and for ease of description, the paragraphs below relate to plot 21 as if the plotted impedance were for a single cardiac cycle. To acquire the time-varying impedance, the control unit typically causes a relatively weak, non-stimuiating current of known amplitude to be passed between the stimulating electrodes. By measuring the voltage between the sensing electrodes, and dividing the voltage by the amplitude of the current, the control unit may derive the impedance between the sensing electrodes.

In general, techniques for blood-flow estimation described below may be applied to impedance measurements over a single cardiac cycle, or alternatively, to impedance measurements over multiple cardiac cycles, e.g., by averaging the impedance as described above. Any reference in the present description and claims to a "systolic period" includes within its scope an average systolic period. Thus, for example, any reference to an impedance value at the beginning or end of a systolic period includes within its scope the average impedance value over the respective beginnings or ends of multiple systolic periods. Analogously, other terms in the description and claims, such as "cardiac cycle," may include within their scope similar averages.

It is noted that, by convention in the field of plethysmography, impedance is plotted such that Z decreases, rather than increases, along the vertical axis. To obviate any possible confusion, Fig. 2 explicitly shows an upward-pointing arrow next to plot 21, accompanied by the expression "Zj.". Fig. 2 also shows a second plot 23, which is derived from plot 21. In particular, the negative of the derivative of Z with respect to time (dZ/dt) is plotted in second plot 23. (Effectively, plot 23 is the straightforward time-derivative of plot 21. However, due to the above-noted "reverse" convention in the plotting of Z, plot 23 actually shows -dZ/dt, rather than dZ/dt.) The data in second plot 23 is typically derived by the control unit.

Time tl is the start of the systolic portion of the cardiac cycle. At tl, Z = Zi, the initial value of Z. As time progresses, changes in the volume of blood between the sensing electrodes, and/or changes in the velocity of the blood, cause changes in Z. The following model, which explains the changes in Z, is presented, for example, in the above-cited reference to Bernstein: AZ(t) = (Ap(t)xL²)/Vi + (pixL²)/AV(t) (equation 1), where AZ(t) = Z(t) - Zj, Vi is the "baseline" volume of blood between the sensing electrodes at tl, AV(t) = V(t) - Vi, pi is the characteristic impedance of blood when the blood is stationary (typically around 150 Ω-cm, although other values may be used), Ap(t) = p(t) - pi, and L (which is explicitly indicated in Fig. 1) is the distance between the sensing electrodes.

Effectively, the model above explains AZ(t) in light of two phenomena. First, as the velocity of blood changes, the characteristic impedance of the blood changes, thus affecting AZ(t). For example, with increasing velocity, Ap(t) comes more negative, thus causing Z to decrease. This first phenomenon is reflected by the term ( Ap(t)xL ^")/Vi in equation 1 . Second, as the volume of blood between the sensing electrodes changes from the baseline value Vi, Z changes. This second phenomenon is reflected by the term (prxL²)/AV(t) in equation 1.

Between tl and time t3, changes in the volume of the blood between the sensing electrodes, and in the velocity of the blood, cause Z to decrease from Zi to a minimum value ΖΜ·

(In line with convention, plot 21 shows ZM as a maximum, rather than a minimum .) At time t.2, between tl and t3, the rate of decrease of Z is at a maximum, i.e., dZ/dt reaches its most negative value, hence, plot 23 shows a maximum, positive (+ve) value of -dZ/dt at t2. Subsequently to t3, changes in volume and/or velocity cause Z to increase. At time t4, the time at which the aortic valve closes, the rate of increase of Z reaches a maximum, ie., dZ/dt reaches its most positive value; hence, plot 23 shows a minimum, negative (-ve) value of -dZ/dt at t4. Z continues to increase until time t5, the time at which the pulmonic valve closes and the systolic portion of the cardiac cycle ends. Since i5 marks the end of the systolic period, the value of Z at t5 is referred to as the fma! value of Z, Zp.

Using the impedance-related data, the control unit computes a measure of blood flow into the portion of the subject's body that is between the electrodes. For example, the controi unit may compute a flow rate (expressed, for example, in mL/minute) over the systolic period. First, the control unit computes an estimated volume of blood flow into the region of interest (the portion of the subject's body between the electrodes) during the systolic period. This volume is then multiplied by the subject's heart rate during the systolic period, to arrive at the flow rate. (In some embodiments, the control unit does not compute flow rates at all, but rather, uses the "raw" volume measures to control the electrostimulation.)

As noted above, the measure of blood flow may be computed based on a single systolic period, or alternatively, based on an average of the measured impedance over several systolic periods. Alternatively, the control unit may compute separate estimated volumes of blood flow for each of several systolic periods, compute an average of the estimated volumes, and then compute a flow rate based on the average volume. Alternatively, the control unit may compute separate flow rates for each of several systolic periods, and then compute the average of these flow rates.

Below, a particular method for estimating the volume of blood flow during a systolic period is described. It is noted that, notwithstanding the below, other methods may be used by the control unit.

By way of introduction, the above-cited reference to Nyboer uses a technique known as backward extrapolation to calculate blood-flow volume. In brief, Nyboer first ignores the effect of changing velocity, and assumes that ΔΖ is affected only by the second term in equation 1, i.e.,

ΔΖ(ί) = (pixL²)/AV(t) (equation 2).

By inverting equation 2, and with a further refinement, Nyboer arrives at the equation AVmax ^;:; -((pi^xL^")/Zo ^")ΔΖ_ηιαχ (equation 3), where AV_max is the total (or "maximum") volume of blood that enters the region of interest during the systolic period, AZ_max is the maximum change in Z that theoretically could be attained if blood flow from the region of interest were prevented, and Zo is the mean of Zj and the value of Z at the end of the cardiac cycle. (In Fig. 2, Z is shown returning to Z\ at the end of the cardiac cycle, such that Zo = (Zi + Zi)/2 = Zi.) Nyboer then uses backward extrapolation to estimate AZ_ma . Beginning with ZF at t5, Nyboer extrapolates backward in time along a first extrapolation line 25, whose slope KIBE is the value of -dZ/dt at t-4. (As noted above, -dZ/dt reaches a minimum at t4, such that ITIBE may be alternatively written as min(- dZ/dt)). The value ΖβΕ of first extrapolation line 25 at tl is therefore raBE^xT + ZF, where T = t5 - tl . ZBE i s subtracted from Z\ to yield AZ_fflax Thus, per Nyboer,

AVmax = -(ί ί ΐ ο½/Β Κ - Zj) (equation 4).

From experimentation, the inventors have observed that equation 4 consi stently overestimates AV_max. The inventors assume that the overestimation is due to the fact that

Nyboer ignores the first term in equation 1. In other words, Nyboer assumes that the observed changes in Ζ are due only to changes in volume, when in fact, the observed changes are also due to the changing velocity of the blood.

Hence, embodiments of the present invention utilize an adjusted backward extrapolati on from t5. The adj usted backward extrapolation yields a value ZADJ that is greater than ZBE.

Thus, the absolute difference between ZADJ and Zj is less than the absolute difference between ZBE and Zr, and therefore, the AV_max that is computed in accordance with embodiments of the present invention is less than the AV_max that is computed per Nyboer.

For example, in some embodiments, a second extrapolation line 27 is used instead of first extrapolation line 25, second extrapolation line 27 having a slope mADJ that i s less negative than πτβΕ- Typically, mADJ is the value of -dZ/dt at a time t8 that is different from t4. In other words, ZADJ = -dZ/dt|t8^xT + ZF, where -dZ/dtjtg is the value of -dZ/dt at t8. In some embodiments, t8 is offset from t3 by the same amount of time At by which t3 is offset from t2, such that t.8 = 2t3 - 12.

Reference is again made to Fig. 1 . As described above, using AVma , the control unit computes a measure of blood flow, and, in response to the computed measure, controls the electrodes, i .e., controls the electrostimulation of the subj ect that is delivered by the electrodes.

For example, the control unit may compute a flow rate, by multiplying AVmax by the subj ect's heart rate. The control unit may then compare the flow rate to a threshold, which may be provided, for example, by the subj ect's physician. If the flow rate is less than the threshold, the control unit may increase electrostimulation of the subject, by beginning to execute an electrostimulation program, or, if an electrostimulation program is already in session, increase the amplitude, frequency, and/or width of the electrostimulation pulses, and/or otherwise change the shape of the pulses such as to increase the stimulation . (Alternatively, as noted above, the control unit may omit the calculation of the flow rate, and simply compare AV_max to a suitable threshold.)

Alternatively or additionally, the control unit may communicate the computed measure to processor 24. In response to the received measure, the processor may prompt the subject to increase the electrostimulation, by, for example, beginning to execute an electrostimulation program, adjusting a parameter of the electrostimulation program, and/or adjusting a location of the electrostimulation, e.g., by adjusting the position of the cuff. To prompt the subject, the processor may display a suitable message on a display 36 of the mobile device, and/or output a suitable audio message.

Conversely, if the flow rate i s greater than the threshold, the control unit may reduce the electrostimulation, by, for example, reducing the amplitude, frequency, and/or width of the electrostimulation pulses, or by stopping the electrostimulation entirely.

As noted above, in some embodiments, electromyographic measurements of the subject are obtained, from the electrodes, by the control unit. In such embodiments, the electrostimulation may be controlled in response to the electromyographic measurements, alternatively or additionally to the computed measure of blood flow. For example, the control unit may increases the stimulation intensity until the electromyogra hic measurements show the expected degree of muscle contraction. Alternatively or additionally, the processor of the mobile device may prompt the subject to adjust the position of the cuff (and hence, the stimulating electrodes), until the electromyographic measurements show the expected degree of muscle contraction.

Alternatively or additionally, an electromyographic measurement may be obtained at each of a plurality of different electrostimulation intensities. The control unit may then ascertain that up to a certain threshold ("supramaximal") intensity, the signal energy of the electromyographic measurements increases with increasing stimulation intensity, but beyond the threshold intensity, no increase in signal energy is observed. Further to identifying the threshold intensity, the intensity of the electrostimulation program may be set slightly less than the threshold. In this manner, a maximal electrostimulation effect may be achieved, without consuming excess power. For example, to identify the threshold intensity, the stimulation intensity may be periodically increased by a particular offset. Upon ascertaining that the increase in intensity has not caused an increase in the signal energy of the electromyographic measurement, the latest stimulation intensity may be identified as the threshold intensity. Alternatively, the threshold intensity may be identified by periodically reducing the stimulation intensity until a decrease in the electromyographic signal energy is observed.

Using such electromyographic measurements, the threshold for any relevant parameter of the electrostimulation may be identified, alternatively or additionally to the stimulation intensity. For example, electromyographic measurements may be used to identify the threshold pulse width, i.e., the pulse width at which a maximal stimulation effect is observed.

In some embodiments, techniques known in the art are used to ascertain the body composition of the stimulated portion of the subject's body, and the electrostimulation parameters are set such as to coirespond to the body composition. For example, to stimulate a leg having a relatively high percentage of body fat, the pulse amplitude may be made relatively high.

in some embodiments, system 20 is used to facilitate remote monitoring of the subject. For example, blood-flow measures computed by the control unit may be uploaded by processor 24 to a remote server, and subsequently downloaded for viewing, e.g., in real-time, by physician 38. Alternatively or additionally, the subject himself may monitor the blood-flow measures, by viewing appropriate data displayed on display 36. In response to a decrease in blood flow, processor 24 may generate appropriate alerts for the subject, the physician, and/or any other relevant individual, alternatively or additionally to beginning or adjusting an electrostimulation procedure.

In some embodiments, processor 24 allows the subject to choose between various electrostimulation programs. Alternatively or additionally, processor 24 may update the treatment programs offered to the subject, in response to receiving collective "wisdom of the crowd" feedback or information based on "big data" processing. For example, a remote server may process results from electrostimulation treatment of a plurality of other subjects, and the processor may use, as the default stimulation parameters, stimulation parameters (including, for example, an intensity or duration of stimulation) derived from such processing.

In some embodiments, the measured impedances may be used for monitoring the coupling of the electrodes to the skin, as described, for example, in US Application 14/992,046, filed January 11, 2016, which is incorporated herein by reference. Such monitoring enhances the comfort and safety of the subject. For example, if the measured impedance is sufficiently higher than expected, processor 24 may notify the subject that the cuff has come loose.

In some embodiments, one or more of the computational tasks attributed above to the control unit are instead performed by processor 24. For example, in some embodiments, the control unit simply communicates the measured time-varying impedance to processor 24, without calculating any measure of blood flow. Processor 24 then computes the measure of blood flow, and, in response to the computed measure, issues appropriate instructions to the control unit.

It is noted that techniques for blood-flow monitoring described herein may be practiced even outside the context of electrostimulation. For example, techniques described herein may be used to monitor blood flow in a patient who has recently undergone surgery, and is therefore at heightened risk of DVT.

It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.

Claims

1 . A system, comprising:

a control unit:

a plurality of electrodes connected to the control unit; and

a mobi le device, comprising a processor configured to, when the electrodes are coupled to skin of a subject, wirelessly communicate a control signal to the control unit that causes the control unit to:

compute a measure of flow of blood into a portion of a body of the subject during a period of time, based on impedance measurements acquired, using at least some of the electrodes, during the period of time, and

in response to the computed measure, control at least some of the electrodes.

2. The system according to claim 1 ,

wherein the impedance measurements include a time-varying impedance Z between two of the electrodes over at least one systolic period of a cardiac cycle, and

wherein the control unit is configured to compute the measure by:

using the adjusted backward extrapolation, computing a volume of blood flow that is less than (pL /Zf )^x(min(-dZ/dt)xT + Zp - Zj), where p is 150 Ω-cm, L is a distance between the two electrodes, dZ/dt is a derivative of Z with respect to time, min(-dZ/dt) is a minimum of -dZ/dt over the systolic period, T is a total duration of the systolic period, ZF is a value of Z at the end of the systolic period, Zi is a value of Z at a beginning of the systolic period, and Zo is a mean of Z{ and a value of Z at an end of the cardiac cycle.

3. The system according to claim 2, wherein the control unit is configured to compute the volume by computing (pLⁱ/Zo^i')^x(-dZ/dt|t8^x + ZF - Z j, where -dZ/dtjts is a value of -dZ/dt at a time t.8 during the systolic period that is different from a time during the systolic period at which -dZ/dt = min(-dZ/dt).

4. The system according to claim 3, wherein†,8 =^: 2t3 - t2, where t2 is a time during the systolic period at which -dZ/dt reaches a maximum, and t3 is a time during the systolic period at which Z reaches a minimum.

5. The system according to any one of claims 1-4, wherein the control unit i s configured to, in response to the computed measure being less than a threshold, cause the electrodes to increase electrostimulation of the subject.

6. The system according to any one of claims 1-4, wherein the processor is further configured to:

receive, from the control unit, the computed measure, and

7. The system according to any one of claims 1-4, wherein the control unit is configured to obtain electromyographic measurements of the subject from at least some of the electrodes, and to control at least some of the electrodes in response to the electromyographic measurements.

8. The system according to claim 7, wherein the control unit is configured to:

control the at least some of the electrodes in response to the electromyographic measurements, by setting the parameter of the electrostimulati on to be less than the threshold.

9. A method, comprising:

using a mobile device, wirelessly communicating a control signal to a control unit, the control unit being connected to a plurality of electrodes coupled to skin of a subject; and

using the control unit, in response to the control signal :

computing a measure of flow of blood into a portion of a body of the subject during a period of time, based on impedance measurements acquired, using at least some of the electrodes, during the period of time, and

in response to the computed measure, controlling at least some of the electrodes.

10. The method according to claim 9, wherein the portion of the body of the subject includes a leg of the subj ect.

11. The method according to claim 9,

wherein the impedance measurements include a time-varying impedance Z between two of the electrodes over at least one systolic period of a cardi ac cycle, and

wherein computing the measure comprises: performing an adjusted backward extrapolation from an end of the systolic period, and

using the adjusted backward extrapolation, computing a volume of blood flow

2 2

that is less than (pL /¾ )x(min(-dZ/dt)xT + Zp - ¾), where p is 150 Ω-cm, L is a distance between the two electrodes, dZ/dt is a derivative of Z with respect to time, min(-dZ/dt) is a minimum of -dZ/dt over the systolic period, T is a total duration of the systolic period, Zp is a value of Z at the end of the systolic period, l.\ is a value of Z at a beginning of the systolic period, and ZQ is a mean of L ' \ and a value of Z at an end of the cardiac cycle,

12. The method according to claim 11, wherein computing the volume comprises computing

2 , 2 .

(pL /Zfj )x(-dZ/dt|t8^xT + ZF - Zi), where -dZ/dt|t8 is a value of -dZ/dt at a time t8 during the systolic period that is different from a time during the systolic period at which -dZ/dt ^:= min(-dZ/dt).

13. The method according to claim 12, wherein t8 = 2t3 - t2, where t2 is a time during the systolic period at which -dZ/dt reaches a maximum, and t3 is a time during the systolic period at which Z reaches a minimum.

14. The method according to any one of claims 9-13, wherein controlling the at least some of the electrodes comprises, in response to the computed measure being less than a threshold, causing the electrodes to increase electrostimulation of the subject.

15. The method according to any one of claims 9-13, further comprising, using the mobile device:

receiving, from the control unit, the computed measure, and

in response to the computed measure, prompting the subject to adjust a location of at least one of the electrodes.

16. The method according to any one of claims 9-13, further comprising, using the control unit:

obtaining electromyographic measurements of the subject from at least some of the electrodes, and

controlling at least some of the electrodes in response to the electromyographic measurements.

17. The method according to claim 16, wherein the obtaining comprises obtaining a respective one of the electromyographic measurements at each of a plurality of different values of an electrostimulation parameter,

wherein the method further comprises identifying a threshold one of the values, by ascertaining that a signal energy of the electromyographic measurements does not increase as the value of the parameter is increased beyond the threshold, and

wherein controlling the at least some of the electrodes in response to the electromyographic measurements comprises setting the parameter of the electrostimulation to be less than the threshold.

18. A computer software product comprising a tangible non-transitory computer-readable medium in which program instructions are stored, which instructions, when read by a processor of a mobile device, cause the processor to wirelessly communicate a control signal to a control unit that is connected to a plurality of electrodes coupled to skin of a subject, the control signal causing the control unit to:

in response to the computed measure, control at least some of the electrodes.

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