Non-invasive probe for detecting medical conditions

A non-invasive probe for application to a body part, such as a finger, toe or limb, for the detection of a medical condition of the subject includes a housing defining a compartment closed at one end and open at the opposite end for receiving the distal end of the subject's body part including its terminal-most extremity, a sensor for sensing a predetermined condition of the body part after being received within the compartment, and a removable liner lining the inner surface of the housing, to facilitate the insertion of the body part into the compartment. The described probe is one which senses changes in the peripheral arterial tone as manifested by changes in the pulsatile arterial blood volume and/or changes in the oxygen saturation level in a terminal extremity of a body part, and includes a number of other features particularly useful in such probes.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to non-invasive probes for application to a body part of a subject for the detection of a medical condition of the subject. The invention is particularly useful in finger probes, such as described in U.S. Pat. Nos. 6,319,205 and 6,322,515, and in International Applications PCT/IL99/00292 (published Dec. 16, 1999 as International Publication No. WO 99/63884), PCT/IL00/00307 published Dec. 14, 2000 as International Publication No. WO 00/74551), PCT/IL00/00403 (published Jan. 18, 2001 as International Publication No. WO 01/03569; and PCT/IL01/00970, filed Oct. 22, 2001. The invention is therefore described below with respect to the probes described in the above patents and applications (hereinafter, “the above-identified U.S. patents and International Patent Applications”), but it will be appreciated that the invention could also be advantageously used in other types of probes.

The above-identified U.S. patents and International Patent Applications disclose various probe constructions, methods and apparatus for the non-invasive detection of a medical condition of a subject, particularly by monitoring changes in the peripheral arterial tone as manifested by changes in the pulsatile arterial blood volume in a terminal extremity of a body part, e.g., a digit (finger or toe) of the subject. The various medical conditions detected by such probes, as described therein, include mycardial ischemia, sleep apnea, endothelial dysfunction (ED), sleep disorders, mental stress, sympathetic nervous system reactivity, blood pressure, etc.

In general, the probes described in the above-identified U.S. patents and International Applications include a housing defining a compartment closed at one end and open at the opposite end for receiving the distal end of the subject's body part, such as a finger or toe, including its terminal-most extremity, and a sensor for sensing a predetermined condition of the body part after being received within the compartment. The preferred embodiments described therein are particularly useful for monitoring peripheral arterial tone in a subject's finger, and for this purpose, they include pressurizing means for applying a static pressure field substantially uniformly around the distal end of the subject's finger, including its terminal-most extremity. The pressure field is of a predetermined magnitude sufficient to substantially prevent distention of the venous vasculature, uncontrolled venous backflow and retrogade shockwave propagation into the distal end of the finger, and to partially unload the wall tension of, but not to occlude, the arteries in the distal end of the finger when at heart level or below. The probe sensor senses changes in the distal end of the subject's finger (or other body part) related to changes in volume therein due to pulsatile changes in instantaneous blood volume related to arterial tone.

Further particulars as to the construction of such probes, and the various medical conditions for which they may be used, are available in the above-identified U.S. patents and International Patent Applications, the contents of which are hereby incorporated by reference herein.

Because of the potential diagnostic capabilities of such probes, considerable research and development has been conducted to improve their construction, to make them more convenient to use, and to extend their diagnostic range.

BRIEF SUMMARY OF THE PRESENT INVENTION

The present invention relates to a number of improvements in non-invasive probes in general, which improvements are particularly useful in the probes described in the above-identified U.S. patents and International Applications, and which produce a number of advantages when implemented in such probes as will be more particularly described below.

According to one aspect of the present invention, there is provided a non-invasive probe for application to a body part of the subject for the detection of a medical condition of the subject, comprising: a housing defining a compartment closed at one end and open at the opposite end for receiving the subject's body part; a sensor for sensing a predetermined condition of the body part after being received within the compartment; and two removable liners of a low-friction sheet material lining two inner surfaces of the housing to face opposite sides of the body part when received in the compartment, each of the liners including an internal portion located within the housing, and an external portion extending externally of the housing to facilitate the slidable withdrawal of each liner from the housing after the body part has been inserted into the compartment.

According to another aspect of the present invention, there is provided a probe for application to a body part of a subject for the non-invasive detection of a medical condition of the subject, comprising: a housing defining a compartment closed at one end and open at the opposite end for receiving the distal end of the subject's body part including its terminal-most extremity; and a sensor for sensing a predetermined condition of the body part after being received within the compartment; the housing including: an inner casing; an inner membrane within the casing and defining an inner chamber for receiving a fluid to apply a predetermined static pressure to the body part when received within the compartment; an outer membrane over the outer surface of the inner casing and defining therewith an outer chamber communicating with the inner chamber via an opening in the inner casing effective to cause said predetermined static pressure applied by the inner membrane to be substantially unaffected by the size of the body part inserted into said compartment or by volume changes of the body part inserted therein; and an outer casing facing the outer surface of the outer membrane and defining therewith a third chamber; the outer casing including a vent opening venting the third chamber to the atmosphere.

According to further features in a described preferred embodiment, the probe further includes a pressure transducer for monitoring pressure changes within the third chamber via an opening in the outer casing.

According to yet another aspect of the present invention, there is provided a probe for application to a body part of a subject for the non-invasive detection of a medical condition of the subject, comprising: a housing defining a compartment closed at one end and open at the opposite end for receiving a distal end of the subject's body part including its terminal-most extremity; the housing including a casing, and an inner membrane within the casing defining, with the inner surface of the casing, a chamber for receiving a fluid to apply a predetermined static pressure to the body part when received within the compartment; a restraining member within the compartment to restrain the membrane from expelling the body part from the chamber when the chamber is pressurized by the static pressure; and a sensor for sensing a predetermined condition of the body part after being received within the compartment; the restraining member including an annular ring adjacent to the open end of the housing, and a plurality of arms extending axially within the compartment and terminating short of the closed end of the housing, and thereby short of the terminal-most extremity of the body part when received within the compartment.

According to further features in a described preferred embodiment, the sensor is an optical sensor including a light source and a light detector located externally of the compartment, and the arms of the restraining member include a light guide for guiding light into the interior of the compartment from the light source externally of the compartment, and for guiding light from the interior of the compartment to the light detector located externally of the compartment.

According to yet another aspect of the present invention, there is provided a probe for application to a body part of a subject for the non-invasive detection of a medical condition of the subject, comprising: a housing defining a compartment closed at one end and open at the opposite end for receiving a distal end of the subject's body part including its terminal-most extremity; the housing including a casing and a membrane within the casing and defining a chamber for receiving a fluid to apply a predetermined static pressure to the body part when received within the compartment; a restraining member within the compartment to restrain the membrane from expelling the body part from the chamber when the chamber is pressurized by the static pressure; and a sensor for sensing a predetermined condition of the body part after received within the compartment; the membrane being part of an inflatable elastic bag located within the housing and engaged by the restraining member to define the compartment after receiving the body part of the subject; the casing including an opening for venting the space between the elastic bag and the inner face of the casing.

According to a still further aspect of the present invention, there is provided a probe for application to a body part of a subject for the non-invasive detection of a medical condition of the subject, comprising: a housing defining a compartment closed at one end and open at the opposite end for receiving a distal end of the subject's body part including its terminal-most extremity; the housing including a casing, an inner membrane within the casing and defining an inner chamber for receiving a fluid to apply a predetermined static pressure to the body part when received within the compartment, and an outer membrane defining an outer chamber communicating with the inner chamber via an opening through the casing effective to cause the predetermined static pressure applied by the inner membrane to be substantially unaffected by the size of the body part inserted into the compartment or by volume changes of the body part inserted therein; a restraining member within the compartment to restrain the inner membrane from expelling the body part from the inner chamber when the inner chamber is pressurized by the static pressure; and a sensor for sensing a predetermined condition of the body part after received within the compartment; the restraining member including an annular ring facing the open end of the housing, and a plurality of arms extending axially within the compartment; the annular ring being located inwardly of the open end of the housing to define, with an inner section of the inner membrane, an inner section of the compartment for receiving the body part; the inner membrane including an outer section defining an outer section of the compartment for receiving the body part, and an outer section of the inner chamber for applying the static pressure to the body part when received in the compartment.

As will be described more particularly below, this feature provides a number of advantages, including a reduction in the tendency for the body part (e.g., finger) to be partially expelled from the probe.

According to a still further aspect of the present invention, there is provided a probe for application to a body part of a subject for the non-invasive detection of a medical condition of the subject, comprising: a housing defining a compartment closed at one end and open at the opposite end for receiving a distal end of the subject's body part including its terminal-most extremity; and a sensor for sensing a predetermined condition of the body part after being received within the compartment; the housing including: an inner casing; an inner membrane within the inner casing and defining an inner chamber for receiving a fluid to apply a predetermined static pressure to the body part when received within the compartment; an outer membrane over the outer surface of the inner casing and defining herewith an outer chamber communicating with the inner chamber via an opening in the inner casing; and a retraining member within the compartment; the inner and outer membranes being parts of an inflatable elongated elastic bag; one end of the elongated elastic bag being received over the outer surface of the casing to constitute the outer membrane defining the outer chamber; the opposite end of the elongated elastic bag being received within the casing to constitute the inner membrane engageable by the restraining member and defining the inner chamber communicating with the outer chamber via an opening in the casing.

According to further features in the described preferred embodiments of this aspect of the invention, the casing and the elongated elastic bag are so dimensioned that the one end of the elongated elastic bag, when received over the casing to define the outer chamber, is pre-tensioned sufficient to reduce diffusion of the fluid through the wall of the bag by reducing the static pressure when the body part is not received within the compartment, but not to substantially affect the deform ability of the inner membrane by pulsatile volume changes in the body part when received in the compartment.

In one described preferred embodiment, the inner chamber is partially filled with a supporting medium, and is at a fluid pressure below the predetermined static pressure, such that the added volume of the distal end of the subject's body part, when received within the compartment, produces the predetermined static pressure applied to the body part. As one example, the supporting medium may be or include a spongy body.

In another described preferred embodiment, the probe includes a pair of bistable elastic spring leaves carried by the casing and disposed within the inner chamber on opposite sides thereof; each of the bistable elastic spring leaves being movable to a first stable position projecting away from the casing inner surface into the inner chamber for pre-tensioning the membranes to reduce diffusion of the fluid through the membranes by the fluid pressure within the elongated elastic bag; each of the bistable elastic spring leaves being movable to a second stable position in contact with the casing inner surface to accommodate the subject's body part when introduced into the compartment.

According to a still further aspect of the present invention, there is provided a probe for the non-invasive detection of a medical condition of a subject, comprising: a housing defining a compartment closed at one end and open at the opposite end for receiving a limb of the subject including the distal end of the limb; an inner membrane within the housing and defining an inner chamber for receiving a fluid to apply a predetermined static pressure to the limb including the distal end thereof within the compartment; a restraining member within the compartment; and a sensor within the compartment for sensing a predetermined condition of the distal end of the limb within the compartment.

According to one described embodiment, the predetermined static pressure is produced by fluid self-contained within the probe, and in another described embodiment, it is produced by a fluid supplied from a fluid system external to the probe.

According to further features in this aspect of the invention, the compartment defined by the housing, and the inner chamber defined by the inner membrane, are divided into a plurality of sections, including a distal section at the closed end of the compartment for receiving the distal end of the limb, and at least one proximal section of the opposite open end of the compartment for receiving one or more proximal regions of the limb; the distal section and/or proximal sections of the compartment being subjected to the predetermined static pressure and including the sensor or sensors for sensing the predetermined condition of the distal end of the limb.

The proximal section and the distal section, or any of the intervening sections, of the compartment are also subjected to a predetermined static pressure, and any of such sections may incude sensing means for sensing the predetermined condition of the limb in the respective section of the compartment.

As described more particularly below, such a probe may be used to induce ischemia in a patient for evaluating the degree of induced reactive hyperemia for the purpose of determining the endothelial function state of the patient. The ischemia may be induced by applying pressure to at least one of the plurality of sections of the compartment by a fluid supplied from a fluid system external of the probe and of sufficient magnitude to occlude the flow of blood, the measurements of pulsatile volume changes taken during the application of counter-pressure for occluding blood flow being used to ensure that a sufficient level of counter-pressure is being applied to completely occlude the flow of blood.

As will be described more particularly below, the foregoing features, when applied to probes constructed in accordance with above-identified U.S. patents and International Patent Applications, significantly improve the operation of the probe, greatly facilitate its use, and extend its diagnostic capabilities.

Further features and advantages of the invention will be apparent from the description below.

DESCRIPTION OF PREFERRED EMBODIMENTS

FIG. 1illustrates a probe, therein generally designated10, of a construction similar to that described in the above-identified U.S. patents and International Patent Applications for receiving the distal end of a subject's finger, including its terminal-most extremity, and for detecting one or more medical conditions of the subject by monitoring pulsatile blood volume changes in the finger. Briefly, probe10includes a housing containing an inner casing11of thimble shape to define a compartment closed at one end and open at the opposite end for receiving a subject's finger. Probe10further includes a first, inner membrane12defining, with the inner surface of casing11, an inner chamber C1for receiving a fluid to apply a static pressure to the subject's finger when received within the compartment, and a second membrane13defining a second chamber C2communicating with the first chamber C1via openings14through casing11.

As distinguished from the probe constructions described in the above-identified U.S. patents and International Patent Applications, probe10further includes an outer casing15defining a third chamber C3with the second membrane13. This third chamber C3is vented to the atmosphere via an opening16formed in the outer casing15. The provision of the outer casing15, together with its vent opening16, provides a number of important advantages as will be described more particularly below.

Probe10further includes a restraining member, generally designated20, which is located within the compartment defined by casing11and membrane12for receiving the subject's finger. As described in the above-identified U.S. patents and International Patent Applications, restraining member20restrains the inner membrane12from expelling the subject's finger from the compartment when chamber C1is pressurized. Restraining member20may be of the construction as described in the above-cited patents and applications, to include an annular ring21at the open end of the probe10and mounting a U-shaped bar22extending to the closed end of the compartment defined by the inner membrane12and inner casing11, as described in those patents and applications. Preferably, however, the restraining member20is of the construction described below with respect toFIGS. 5 and 6, which construction provides a number of advantages also to be described below.

Probe10further includes an optical sensor30for sensing changes in the optical characteristics of the finger inserted within the compartment of the probe. In this case, the optical sensor30senses the density of the light passing through the skin of the subject's finger inserted within the compartment, and therefore includes a light source31and a light detector32staggered up to 180° with respect to each other. InFIG. 1they are shown as located on the opposite sides of the compartment such that the detector32is displaced 180° with respect to the light source31. The light source31and detector32are externally connected to a measuring system by electrical leads33and a connector34.

Except for the provision of the outer casing15, probe10illustrated inFIG. 1is constructed and used in the manner described in the above-cited U.S. patents and International Patent Applications, and therefore further details of the construction and use of such a probe are not set forth herein.

In accordance with one aspect of the present invention, probe10illustrated inFIG. 1is provided with a removable liner lining the inner surface of the compartment receiving the subject's finger. This liner is of a low-friction sheet material to facilitate the insertion of the subject's finger into the compartment. Such a liner is particularly useful in probes having a self-contained fluid for producing the predetermined static pressure applied to the finger and facilitates the insertion of the subject's finger and provides a low-friction surface between the finger and the inner membrane12under the static pressure. The low-friction property of the liner, together with the manner in which it is disposed between the subject's finger and the inner membrane12, also facilitates the slidable withdrawal of the liner from between the subject's finger and the inner membrane.

As shown inFIG. 1, probe10actually includes two liners,41and42, for lining the two inner surfaces of the housing compartment to face the opposite sides of the subject's finger when inserted therein. Each of the liners41,42includes an external portion, as shown at41aand42a, respectively, extending externally of the outer casing15, and an inner portion including two (or more) folded sections41b,41cand42b,42c, respectively, received within the compartment between the inner membrane12and the subject's finger when inserted into the compartment.

As shown inFIG. 1, the externally-extending portions41a,42aof the liner sheets are temporarily adherent to the outer surface of the outer casing15. This may be done by the provision of spots of adhesive43,44, between the respective liner and the outer casing.

FIG. 2aillustrates the probe10ofFIG. 1after the subject's finger has been inserted into the probe compartment, which insertion is facilitated by the provision of the liner sheets41,42, as described earlier.FIG. 2billustrates the condition as one of the liner sheets42is being withdrawn by grasping its external portion42a, and pulling it outwardly to first release it from its adherence at44to the outer casing15, and then to start its slidable withdrawal from the probe compartment.FIG. 2cillustrates the condition of the probe after liner42has been fully withdrawn, and the other liner41has also been withdrawn in the same manner. Providing the internal portion of each liner with the folded sections41b,41cand42b,42c, as illustrated inFIG. 1, facilitates the slidable withdrawal of each liner.

Including the outer casing15in probe10illustrated inFIG. 1produces a number of advantages. Thus, the outer casing15provides a rigid surface for adhering the removable liner strips41,42, e.g., at the adhesion points43,44. In addition, since the outer casing15encloses the outer membrane13, it provides protection for that membrane, both during the use of the probe, and also during its handling and storage before use and between uses

FIG. 3illustrates a further advantage that may be provided by the outer casing15, in that it enables pulsatile changes in the finger blood volume to be measured simultaneously with changes in the optical density. For this purpose, the probe illustrated inFIG. 3, therein designated50, is provided with a pressure transducer51, communicating, via an opening52in the outer casing15, with chamber C3between the outer casing15and the outer membrane13. In this case, vent opening16in the outer casing15is of relatively small diameter, as shown at16′, so as to retard the equalization of the air pressure within chamber C3to atmospheric pressure. This enables transducer50to measure the slight pressure swings developed in the probe due to the pulsatile blood volume changes in the finger of the subject received within the probe. It will be appreciated that signals developed by transducer50correspond to the pulsatile blood volume changes in the finger and are derived from the probe itself, i.e., without any connection to an external fluid system.

Probe50illustrated inFIG. 3is otherwise constructed as probe10described above with respect toFIG. 1, and includes the optical sensor30, constituted of light source31on one side of the finger and light detector32on the opposite side, for measuring changes in the optical density of the finger resulting from pulsatile blood volume changes in the finger.

It will be appreciated that probe10illustrated inFIG. 1and/or probe50illustrated inFIG. 3, as well as the other probes described below, may be used to measure, not only pulsatile volume changes, but also other changes, e.g., oxygen saturation level, blood pressure, etc., together with, or in lieu of, changes in the pulsatile blood flow through the finger received in the probe, as described in any of the above-identified U.S. patents and International Patent Applications. For example, such probes may include, in addition to the optical sensors or in lieu thereof, Hall Effect or other flow-related electromagnetic sensors, electrical impedance sensors, strain gauge sensors, Doppler sensors, isotope washout sensors, thermal washout sensors, etc. related to changes in the pulsatile blood flow through the finger.

FIG. 4illustrates a probe60, such as described above with respect toFIG. 1, including the above-described optical sensor30, but including a second optical sensor for sensing the optical density of the examined finger at two different locations of the finger. Thus, optical sensor30including light source31and light detector32, monitors changes in the optical density of the palmar region of the finger; whereas the second optical sensor, including light source61and light detector62, monitors changes in the dorsal region of the finger. By thus deriving optical density changes (and other volume-related changes if desired) from histologically different cutaneous regions, probe60can monitor changes in the vascular beds serving predominantly nutritive roles separate and apart from those serving predominantly thermoregulatory roles. Signals derived from each of these sites, and their relationship to each other based on concurrent recordings, may provide further information regarding the responses of the vascular beds to the monitored changes in the physiological state of the subject.

The illustrated probe may be further modified by incorporating into the probe a patient movement detecting device, such as an actigraph.FIG. 4illustrates probe60with the addition of such a device, at63, attached to the outer surface of the outer casing16. It will be appreciated, however, that a movement detecting device could also be included on a wrist-mounted unit, or on a unit mounted on a different part of the subject's body, connected to the finger probe.

FIGS. 5aand5billustrate a modification in the design of the restrainer member (20,FIG. 1) that may be included in the improved probe construction. As indicated earlier, the purpose of the restraining member is to restrain the membrane (12,FIG. 1) from expelling the subject's finger from the probe compartment when chamber C1is pressurized. In the above-identified U.S. patents and International Patent Applications (and also inFIG. 1of the present application), the restraining member20includes an annular ring to be located adjacent to the open end of the housing, and a U-shaped bar to extend towards the closed end of the housing.

In the modified construction of the restraining member shown inFIG. 5, and therein generally designated70, the restraining member also includes an annular ring71to be located adjacent to the open end of the housing. However, instead of a U-shaped member, it includes a pair of arms72,73to extend axially towards the closed end of the housing but terminating short of the closed end, and thereby short of the terminal-most extremity of the subject's finger when received in the probe compartment. Thus, the restraining member70illustrated inFIG. 5is similar to restraining member20described above with respect toFIG. 1, except that the bend at the end of the U-shaped bar22is removed, thereby effectively creating the two arms72,73which are disconnected at their ends.

Such a construction as illustrated inFIG. 5makes the arms72,73more flexible than the U-shaped bar (22inFIG. 1), thereby enabling their free ends to better accommodate the outer contour of the finger received within the probe compartment. This in turn better allows the static pressure field within the inner chamber C1to be more uniformly applied around the complete surface of the finger introduced within the probe compartment.

Arms72,73may be of the same length as the U-shaped bar22in theFIG. 1construction. Preferably, however, they are slightly shorter so as to terminate short of the terminal-most extremity of the finger inserted into the probe. In addition, arms72,73may be of any suitable elastic material, metal or plastic, enabling them to conform to the shape of the underlying surface of the finger, and allowing for a more uniform pressure field to be applied to the finger. Alternatively, there may be more than two arms, of the same lengths or of different lengths, and aligned with each other or staggered with respect to each other so that they do not directly overlap.

The restraining member70shown inFIG. 5amay also be used for mounting the optical or other sensors used within the probe. This is shown inFIG. 5b, wherein the two arms72,73of the restraining member70mount the distal ends of a pair of optical fibers74,75, while the proximal ends of the optical fibers74,75, are mounted on the annular ring71of the restrainer member70. Thus, the distal ends74a,75a, of the optical fibers74,75are disposed within the probe to detect optically-sensitive changes in the subject's finger inserted therein, whereas the proximal ends74b,75bof the optical fibers are disposed externally of the probe to communicate with a light source76and a light detector77, respectively, externally of the probe.

Optical fibers74,75mounted on restraining member70in the probe illustrated inFIG. 5bmay thus be used for guiding light into the interior of the probe compartment from light source76externally of the compartment, and for guiding light from the interior of the compartment to light detector77externally of the compartment for measuring changes in the optical density of the examined finger due to pulsatile blood volume changes, and/or oxygen saturation level changes. Such an arrangement provides a number of advantages. It eliminates the need for having the light source and the light detector located within the probe compartment, thereby avoiding local heating of the finger by the heat of the light source since the light source would be situated remotely from the skin surface being illuminated. In addition, such an arrangement permits a more compact construction for the probe since the electronic elements would not be part of the probe itself.

It will be appreciated that the two arms72,73of the restraining member70may be constructed of the light-conducting material so as to serve both the restraining function and the light guiding function. It will also be appreciated that the arms72,73of the restraining member70can be used for mounting other types of sensors within the probe including their connections to external devices.

FIG. 6illustrates a probe constructed similarly to that ofFIGS. 1 and 3but modified such that the compartment for receiving the subject's finger (or other body part) is divided into inner and outer sections, with the restraining member applied only in the inner section of the probe. For purposes of brevity and facilitating understanding, those elements of the probe illustrated inFIG. 6which are generally similar to those inFIG. 1are identified by the same reference numerals.

Thus, the probe illustrated inFIG. 6, and therein generally designated80, is of a similar construction as inFIG. 1, except the restraining member20is spaced inwardly of the compartment so as to define an inner section of the compartment for receiving the terminal-most part of the subject's finger. Annular ring21of restraining member20is located inwardly of the open end of the housing such that its pair of arms22define, with an inner section12aof the inner membrane12, an inner section of the compartment for receiving the terminal-most part of the subject's finger, and inner section C1aof the inner chamber C1for applying the static pressure to the terminal-most part of the subject's finger. The probe further includes another annular ring81which engages the outer end of the inner membrane12to define an outer section C1bof the inner chamber C1with the outer section12bof the inner membrane12. The outer section12bof the inner membrane12thus defines an outer section of the compartment receiving the subject's finger, and an outer section C1bof the inner chamber for applying the static pressure field to the remainder of the subject's finger receiving within the probe.

As also seen inFIG. 6, the inner casing11of the probe is formed with vent openings14aventing section C1aof the inner chamber C1to the outer chamber C2, and separate venting openings14bfor venting the outer section C1bof the inner chamber C1to the outer chamber C2. In all other respects, the probe illustrated inFIG. 6is otherwise constructed and operates in the same manner as described above.

An important advantage of the construction illustrated inFIG. 6is that such a construction decreases any tendency of the finger from being expelled from the probe by the pressure within the inner chamber C1applied to the finger when the two liner41,42are withdrawn. Thus, as the two liners are withdrawn, the inner section12aof the inner membrane12comes into direct contact with the terminal-most part of the subject's finger to better hold the finger within the probe as the respective liner is withdrawn from between the outermost part of the subject's finger and the outer section12bof the inner membrane12.

It will be appreciated that the restraining member20illustrated inFIG. 6could be of either the U-bend construction or of the free-end construction illustrated inFIGS. 5aand5b, and that the arms could also be used for mounting the sensor30and its connections to locations externally of the probe.

FIG. 6illustrates a further feature that may be included in the probe ofFIG. 6, or in any of the other described probes, namely the provision of a transmitter82mounted for example on one of the arms of the restraining member20as shown inFIG. 6, or at the terminal end of the connecting wiring as shown inFIG. 1by connector34, for transmitting, in a wireless manner, data sensed by the sensor30to a receiver (not shown) externally of the compartment receiving the subject's finger.

FIGS. 7a-7eschematically illustrate a number of probe constructions for application to other body parts of the subject, in particular to a limb of the subject, for detecting a medical condition in accordance with the method of any of the above-identified U.S. patents and International Patent Applications. The probes schematically illustrated inFIGS. 7a-7eare constructed and dimensioned for application to an arm of the subject, as shown inFIGS. 8a-8e, respectively, including the terminal-most extremities of the fingers of the hand. Such probes are suitable for deriving measurements from more extensive tissue regions of the body than the finger probes described earlier, while still conferring the basic advantages of the probe, namely the prevention of distal venous blood pooling, the unloading of wall tension from arterial blood vessels, and the inhibition of retrograde venous shock wave propagation to the actual measurement site.

FIGS. 7aand8aillustrate a probe, therein generally designated110, constituted of a single section dimensioned for receiving the forearm and hand of the subject;FIG. 7bschematically illustrates a probe120constituted of two sections121,122, one dimensioned for receiving the hand and wrist of the subject, and the other part for receiving the forearm of the subject; andFIG. 7cschematically illustrates a probe130also constituted of two sections131,132, but in this case one section131is dimensioned for receiving the hand of the subject, while the other section132is dimensioned for receiving the wrist and forearm of the subject.

FIGS. 7eand8e, respectively, illustrate three-section probes140and150. The closed-end section141,151, preferably covers all the fingers of the hand, whereas the other two sections142,153and152,153, respectively, may vary in dimension according to the particular application.

The probes110-150schematically illustrated inFIGS. 7a-7eand8a-8e, respectively, are of basically the same construction as in the above-identified U.S. patents and International Patent Applications (and in the other probes described herein), except that they would be designed and dimensioned for receiving a limb or part of a limb of the subject, rather than a finger of the subject. Further partitioning of the above described probes into additional sections is possible and may be useful due to the relatively large sample of tissue contained within the probe. Measurements of the pulsatile blood volume signals may be derived from any one or more of the sections illustrated in these probes, using any of the sensing modalities described. The fluid pressure applied to the various sections of the probe could be derived from fluid self-contained within the probe, or from fluid supplied from sources externally of the probe. Another possibility would be to use a fluid self-contained within the probe for applying the fluid pressure to the section at the closed end of the probe receiving the terminal-most part of the limb, and to utilize an external source of fluid for providing the pressure in one or more sections at the opposite open end of the probe receiving the more proximal regions of the limb.FIG. 9illustrates, for purposes of example, such a large-scale probe for receiving the complete hand and wrist of the subject, wherein the pressure-producing fluid is self-contained within the probe itself as previously described. Such a probe may form part of an overall larger probe as illustrated inFIGS. 7a-7eand8a-8erespectively. It may, for example, replace elements121;131;141and142; or151and152, of these figures, whereas the remainder of the large-scale probe may be of the externally pressurized type as described below with respect toFIG. 10.

The probe part illustrated inFIG. 9, and therein generally designated160, also includes an inner casing161having an inner membrane162defining an inner chamber C1; an outer membrane163defining a second chamber C2with casing161and communicating with chamber C1via openings164in the inner casing161; and an outer casing165defining a third chamber C3with membrane163, which chamber is vented to the atmosphere via a vent opening166formed in the outer casing165. Probe160further includes a restraining member, generally designated170, having an annular ring171adjacent to the open end of the probe, and a U-shaped arm172(or a pair of arms, corresponding to arm72,73illustrated inFIG. 5) extending axially within the compartment receiving the subject's hand for restraining the membrane162from expelling the hand when chamber C1is pressurized. Probe160illustrated inFIG. 9is otherwise constructed as described above, or in the above-identified U.S. patents and International Patent Applications, and is operative in the same manner as described therein for monitoring pulsatile blood volume changes, except that these changes are monitored in the complete hand of the subject, rather than merely in the distal portion of the subject's finger.

FIG. 10illustrates a three-section large-scale probe for receiving substantially the complete forearm of the subject. Thus, the large-scale probe illustrated inFIG. 10, and therein generally designated180, includes a housing181having one or more inner membranes182engaged by restraining members, such as restraining member20and one or more annular rings81inFIG. 6, to define three inner chambers183a,183b,183c, for applying predetermined static pressures to the portion of the forearm received in the respective section of the probe. In the probe illustrated inFIG. 10, the three chambers183a-183care supplied by fluid from an external fluid system, in this case a pneumatic system184under the control of a control unit185. The pneumatic system184also outputs electrical signals to a filter/signal conditioning circuit186which signals, after conversion to digital form by an A/D converter187, are processed within processor188which controls the control unit185and also produces a display in a display unit189.

WhileFIG. 10illustrates all three sections of the probe (i.e., containing the three inner chambers183a-183c) as being pressurized from an external fluid system, it will be appreciated that the distal section of the probe (i.e., that containing the distal chamber183a) could be pressurized by fluid from a self-contained source, as inFIG. 9; whereas the other two sections could be supplied with fluid from the external source.

An important advantage of the large-scale probe illustrated inFIGS. 7a-7eand8a-8e, respectively, is that such a probe, particularly one including an external fluid system as shown inFIG. 10, is especially suited, to effect an induced ischemia test for detecting the presence of endothelial dysfunction in a patient, as described in the above-cited International Applications PCT IL00/00403 and PCT/IL01/00970. Such induced ischemia tests are typically applied on the brachial artery of the upper arm. In the conventional method for inducing ischemia, a blood pressure cuff is inflated to above systolic blood pressure on the upper arm. In the process of inflating the blood pressure cuff, a variable amount of blood may pass beyond the venous tourniquet formed by the upper arm blood pressure cuff when the cuff pressure is sub-systolic but above venous blood pressure. This effectively means that a degree of venous pooling may be induced distal to the occlusion cuff. This has the potential of inducing local reflex vascular effects, such as the veno-arteriolar reflex, which may distort the outcome of the test for endothelial dysfunction.

The large-scale probes as illustrated inFIGS. 7a-10may be specifically designed to prevent the occurrence of such venous pooling in the entire measured vascular bed. Such probes would therefore confer substantial advantages for performing the induced ischemia test by controlling the applied pressure field over the entire tissue mass being studied.

When using a large-scale probe as illustrated inFIGS. 7a-10, it is also possible to apply supra-systolic external pressure to effectively empty all the blood vessels within the applied pressure field. That is, the ischemia would be induced by applying pressure to at least one of the plurality of sections of the compartment of the probe by fluid supplied from a fluid system external of the probe and of sufficient magnitude to occlude the flow of blood. The measurements of pulsatile volume changes taken during the application of counter-pressure for occluding blood flow can be used to ensure that a sufficient level of counter-pressure is being applied to completely occlude the flow of blood. The level of pressure can thus be regulated to the appropriate level if necessary. This would add a degree of certainty to the performance of the induced ischemia test.

An additional advantage in the use of such a large-scale probe is that it can allow simultaneous measurements of pulsatile blood volume changes in the distal ends of a plurality of fingers, thereby further increasing the amount of relevant data which can be derived from the measurements. The internal casing161and external casing165in the probe illustrated inFIG. 9, as well as the fore-arm probes illustrated inFIGS. 7a-7e,8a-8eand10, and the finger probes illustrated inFIGS. 1-5, may be rigid. However, they may also be semi-rigid, e.g., stiff but yielding, for patient comfort.

FIG. 11illustrates another probe, therein generally designated210, constructed in accordance with the present invention, andFIGS. 11a-11dillustrate various components of the probe ofFIG. 11. Probe210includes a thimble-shaped casing211open at one end and closed at its opposite end and receiving an elongated elastic bag212folded within casing211and retained therein by a retaining member213. The elongated elastic bag212is more particularly illustrated in its unfolded form inFIG. 11a, and in its folded form inFIG. 11b. The interior of elastic bag212defines an inner chamber C1, whereas the space between the surface of the elastic bag and the inner surface of casing211defines a second chamber C2. Chamber C2is vented to the atmosphere by opening214in casing211.

Retainer member213is more particularly illustrated inFIG. 11c, wherein it will be seen that it includes an annular ring213aadjacent to the open end of the housing defined by casing211, and a pair of arms213bextending axially within the housing but terminating short of the close-end of the housing defined by casing211. Restraining member213may be of the construction described above inFIG. 1, wherein the arms213bare constituted of a U-shaped member; preferably, however, it is of the construction as described above with respect toFIGS. 5 and 6, wherein the arms213bare two separate arms each terminating short of the closed end wall of the housing defined by casing211. An external ring214, shown inFIG. 11d, applied around the annular ring213aof the restraining member213, clamps the opposite ends of the folded elastic bag212to the annular ring213e.

Probe210illustrated inFIG. 11further includes removable liner strips215,216, corresponding to the removable liner strips41,42inFIG. 1. These liner strips, which temporarily adhere to the outer surface of casing211by spots of adhesive217,218, facilitate the insertion of the subject's finger (or other body part) into the probe compartment, in the same manner as described above with respect toFIGS. 1 and 2a-2c.

Various types of sensors can be included within the probe, not only optical sensors as shown inFIGS. 1,3and, but also other types of sensor for measuring changes in the pulsatile blood volume and/or in the oxygen saturation level, as described above and/or in the above-identified U.S. patents and International Patent Applications.

The elastic bag212may be filled with a gas or liquid, or at least partially filled with a liquid. The advantage of using a liquid rather than a gas is that the diffusion rate through the walls of the elastic bag tends to be higher for gasses than for liquids, and therefore it would be possible to maintain a positive pressure within the bag for longer periods of time using a liquid.

It will thus be seen that an elongated elastic bag may be used in a probe having a self-contained fluid in the two chambers, corresponding to chambers C1, C2inFIG. 1, which communicate with each other via an opening in the casing (e.g., openings14in casing11,FIG. 1). When using such an inflatable elastic bag, it would be desirable to reduce diffusion of the self-contained fluid through the walls of the elastic bag in order to maintain a positive pressure within the bag for longer periods of time. In addition to using a liquid as at least a part of the fluid filling the bag as described above, other means may be used for reducing the diffusion rate through the walls of the elastic bag.

FIGS. 12a-12dillustrate the components of another probe construction utilizing an elongated elastic bag220for self-containing the fluid. One end220aof elastic bag220is received over the outer surface of a rigid casing221(FIG. 12b), corresponding to casing11inFIG. 1, formed with a plurality of openings222, corresponding to openings14inFIG. 1. To facilitate the application of end220aof bag220around the outer surface of casing221, the end220aof the bag is formed with an opening, shown at223inFIG. 12a, which is sealed after that end of the bag has been applied over the casing221, as shown at223′ inFIG. 12b.

The opposite end220bof elastic bag220is then received within the casing221and is retained therein by retainer member224. As shown inFIG. 12c, retainer member224includes an annular ring224aand a U-shaped bar224b, as described above with respect toFIG. 1, but may also be of the modified construction described above with respect toFIGS. 5aand5band6.

When the elastic bag220and the retainer member224are assembled with respect to the casing221, as illustrated inFIG. 12d, the bag may be inflated with the fluid, e.g., a gas or liquid, to produce the predetermined static pressure field to be applied to the subject's finger when received within the probe. After the bag is so inflated, it may be sealed. It will be appreciated that when the probe is so assembled, end220bof the elastic bag220serves the equivalent of the inner membrane (12,FIG. 1) defining the inner chamber C1with the inner surface of casing221; and that end220aof the elastic bag serves as the second membrane (corresponding to13,FIG. 1) which cooperates with the outer surface of the casing221to define the second chamber C2communicating with the first chamber C1via the openings222in the casing221. It will also be appreciated that the retainer member224retains end220bof bag220within the probe and defines the compartment therein for receiving the subject's finger to be monitored.

For the sake of simplifying the drawings,FIG. 12ddoes not illustrate the sensor or sensors (corresponding to sensor30,FIG. 1) within the probe, the liner strips to facilitate insertion of the subject's finger into the probe, or the outer casing corresponding to casing15inFIG. 1.

The elongated elastic bag220is constructed and dimensioned such that, when its end220ais applied around the outer surface of the casing221, that end of the elastic bag is pre-tensioned. Pre-tensioning this end of the elastic bag reduces the diffusion rate of the fluid through the walls of the bag, and thereby enables a positive fluid pressure to be retained within the bag for longer periods of time. Such a construction also allows a larger volume of fluid to be retained at an effective zero pressure since any residual stretched wall tension at end220aof the bag is unloaded when it collapses to the point of coming to rest on the outer wall of casing221and the effective probe pressure is zero.

FIG. 13illustrates a self-contained fluid type probe, generally designated310, also including an elongated elastic bag320applied over a rigid casing321as described above to define the outer membrane by one end320aof the bag, and the inner membrane by the opposite end320bof the bag, with the latter end being retained in place by retainer member324, as described above.FIG. 13, however, also illustrates the outer casing315, the sensor light source331and light detector332within the probe, and the removable liners341,342, corresponding to elements15,30,41and42, respectively inFIG. 1.

FIG. 13, however, further illustrates the provision of a supporting medium within the inner chamber defined by end320bof the elastic bag320. This supporting medium is shown inFIG. 13as being in the form of sponge-rubber inserts350. These inserts should be of sufficient mechanical strength to support the end320bof the elastic bag320, serving as the inner membrane defining the inner chamber C1with the inner surface of the casing321, and should be of sufficient volume so as to partially fill this chamber such that the added volume of the subject's finger, when received within the probe, produces the predetermined static pressure to be applied to the subject's finger. Thus, the volume of the fluid (e.g., gas) initially included within the chamber C1can be significantly reduced, thereby reducing the pressure within the chamber before the subject's finger is inserted into the probe. Such an arrangement is therefore also effective to reduce the diffusion rate of the fluid when the probe is not in use, and thereby maintains the pressure within the probe for longer periods of time.

The supporting medium partially filling the chamber may be of material other than sponge rubber, such as a low-density collapsible foam-like matrix which partially fills the chamber with a minimum effect on the deform ability of the membrane by the pulsatile blood volume changes in the subject's finger when received within the probe.

FIGS. 14a-14care side views, andFIGS. 15a-15care end views, schematically illustrating another manner, useful in a self-contained fluid type probe, for reducing the diffusion rate of the fluid when the probe is not in use. This technique is based on pre-tensioning the membrane prior to its use so as to prevent it from compressing the contained fluid, thereby reducing the effective pressure within the probe. This reduces the diffusion rate through the membrane when the probe is not in use.

The probe schematically illustrated inFIGS. 14a-15c, and therein designated410, also includes a casing411having an inner membrane412defining an inner chamber C1within it, and an outer membrane413defining an outer chamber C2(best seen inFIGS. 14band15b) with the outer surface of the casing, with the two chambers in communication with each other via openings (not shown, but corresponding to openings14inFIG. 1).

Such a probe may also include a restraining member, a sensor, and the other elements of the probe as illustrated inFIG. 1but not shown inFIGS. 14a-15cfor purposes of simplifying the drawings.

In order to reduce the diffusion rate of the fluid within the two chambers C1, C2, the probe is provided with a pair of bistable elastic spring leaves451,452, carried by casing441and disposed within the inner chamber C1on opposite sides of that chamber. Each of the bistable elastic spring leaves451,452is movable to a first stable position, as shown inFIGS. 14aand15a, projecting away from the inner surface of the casing441, or to a second stable position, as shown inFIGS. 14band15b, in contact with the inner surface of the casing411. Thus, when the bistable elastic elements451,452are in their inner positions shown inFIGS. 14aand15a, they tend to expand chamber C1and thereby pre-tension the membranes, reducing the diffusion rate through the membranes, when the probe is not in use.

When the probe is to be used, the bistable elastic spring leaves451,452are snapped to their outer positions, shown inFIGS. 14band15b, into engagement with the inner surface of the casing411. This allows the user to insert a finger into the probe which displaces fluid from chamber C1and expands chamber C2to produce the predetermined static pressure in chamber C1applied to the finger.

After the probe has been used, the user may remove the finger and leave the bistable elastic spring leaves in their outer positions, as shown inFIGS. 14cand15c, wherein they pre-tension the membrane, and thereby reduce the diffusion rate on the fluid. If the probe is not to be used again within a short period of time, the bistable elastic spring leaves451,452may be snapped to their inner positions, as shown inFIGS. 14a,15a.

While the invention has been described with respect to several preferred embodiments, it will be appreciated that these are set forth merely for purposes of example, and that many other variations, modifications and applications of the invention may be made.