Abstract:
An optical sensor includes photoemitter and photodetector elements at multiple spacings (d 1 , d 2 ) for the purpose of measuring the bulk absorptivity (α) of an area immediately surrounding and including a hemodialysis access site, and the absorptivity (α o ) of the tissue itself. At least one photoemitter element and at least one photodetector element are provided, the total number of photoemitter and photodetector elements being at least three. The photoemitter and photodetector elements are collinear and alternatingly arranged, thereby allowing the direct transcutaneous determination of vascular access blood flow.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]    The present patent application is a continuation-in-part of application Ser. No. 09/084,958, filed May 28, 1998, which is a continuation of application Ser. No. 08/479,352, filed Jun. 7, 1995 (now U.S. Pat. No. 5,803,908), which is a continuation of application Ser. No. 08/317,726, filed Oct. 4, 1994 (now U.S. Pat. No. 5,499,627), which is a divisional of application Ser. No. 08/011,882, filed Feb. 1, 1993 (now U.S. Pat. No. 5,372,136), which is a continuation of application Ser. No. 07/598,169, filed Oct. 16, 1990 (abandoned); and a continuation-in-part of application Ser. No. 09/244,756, filed Feb. 5, 1999, which claims the benefit of Provisional Application No. 60/073,784, filed Feb. 5, 1998), all of which are incorporated herein by reference in their entireties. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    The present invention relates to apparatus for non-invasively measuring one or more blood parameters. More specifically, the invention relates to apparatus for the transcutaneous measurement of vascular access blood flow. The invention can also be used for precise access location, as a “flow finder,” and also can be used to locate grafts and to localize veins in normal patients for more efficient canulatization.  
           [0004]    2. Related Art  
           [0005]    Routine determination of the rate of blood flow within the vascular access site during maintenance hemodialysis is currently considered an integral component of vascular access assessment. While the relative importance of vascular access flow rates and venous pressure measurements in detecting venous stenoses is still somewhat controversial, both the magnitude and the rate of decrease in vascular access flow rate have been previously shown to predict venous stenoses and access site failure. The traditional approach for determining the vascular access flow rate is by Doppler flow imaging; however, these procedures are expensive and cannot be performed during routine hemodialysis, and the results from this approach are dependent on the machine and operator.  
           [0006]    Determination of the vascular access flow rate can also be accurately determined using indicator dilution methods. Early indicator dilution studies determined the vascular access flow rate by injecting cardiogreen or radiolabeled substances at a constant rate into the arterial end of the access site and calculated the vascular access flow rate from the steady state downstream concentration of the injected substance. These early attempts to use indicator dilution methods were limited to research applications since this approach could not be routinely performed during clinical hemodialysis. It has long been known that in order to determine the vascular access flow (ABF) rate during the hemodialysis procedure, the dialysis blood lines can be reversed (by switching the arterial and venous connections) to direct the blood flow within the hemodialysis circuit in order to facilitate the injection of an indicator in the arterial end of the access site and detect its concentration downstream (N. M. Krivitski, “Theory and validation of access flow measurements by dilution technique during hemodialysis,”  Kidney Int  48:244-250, 1995; N. M. Krivitski, “Novel method to measure access flow during hemodialysis by ultrasound velocity dilution technique,”  ASAIO J  41:M741-M745, 1995; and T. A. Depner and N. M. Krivitski, “Clinical measurement of blood flow in hemodialysis access fistulae and grafts by ultrasound dilution,”  ASAIO J  41:M745-M749, 1995)). D. Yarar et al.,  Kidney Int.,  65: 1129-1135 (1999), developed a similar method using change in hematocrit to determine ABF. Various modifications of this approach have been subsequently developed. While these latter indicator dilution methods permit determination of the vascular access flow rate during routine hemodialysis, reversal of the dialysis blood lines from their normal configuration is inconvenient and time-consuming since it requires that the dialyzer blood pump be stopped and the dialysis procedure is relatively inefficient during the evaluation of the flow rate which can take up to twenty minutes. Furthermore, some of these indicator dilution methods also require accurate determination of the blood flow rate.  
           [0007]    Clinical usefulness and ease of use are major developmental criteria. From a routine clinical point of view the need to design a simple sensor, easily attached to the patient, requiring no line reversals, no knowledge of the dialysis blood flow rate, Q b , and transcutaneously applied to skin, thereby accomplishing the measurement within a total of 1-2 minutes, is crucial to have repeated, routine meaningful ABF trend information, whereby access health is easily tracked.  
         SUMMARY OF THE INVENTION  
         [0008]    It is therefore an object of the present invention to provide apparatus for non-invasively measuring one or more blood parameters.  
           [0009]    It is another object of the present invention to provide an optical hematocrit sensor that can detect changes in hematocrit transcutaneously.  
           [0010]    It is still another object of the invention to provide an optical hematocrit sensor that can be used to determine the vascular access flow rate within 2 minutes and without reversal of the dialysis blood lines or knowledge of Q b , all transcutaneously.  
           [0011]    These and other objects of the invention are achieved by the provision of an optical sensor including complementary emitter and detector elements at multiple spacings (d 1 , d 2 ) for the purpose of measuring the bulk absorptivity (α) of the volume immediately surrounding and including the access site, and the absorptivity (α o ) of the tissue itself.  
           [0012]    In one aspect of the invention, the optical sensor system comprises an LED of specific wavelength and a complementary photodetector. A wavelength of 805 nm-880 nm, which is near the known isobestic wavelength for hemoglobin, is used.  
           [0013]    When the sensor is placed on the surface of the skin, the LED illuminates a volume of tissue, and a small fraction of the light absorbed and back-scattered by the media is detected by the photodetector. The illuminated volume as seen by the photodetector can be visualized as an isointensity ellipsoid, as individual photons of light are continuously scattered and absorbed by the media. Because a wavelength of 805 nm-880 nm is used, hemoglobin of the blood within the tissue volume is the principal absorbing substance. The scattering and absorbing characteristics are mathematically expressed in terms of a bulk attenuation coefficient (a) that is specific to the illuminated media. The amount of light detected by the photodetector is proportional via a modified Beer&#39;s law formula to the instantaneous net a value of the media.  
           [0014]    When the volume of tissue illuminated includes all or even part of the access, the resultant a value includes information about both the surrounding tissue and the access itself. In order to resolve the signal due to blood flowing within the access from that due to the surrounding tissues, the sensor system illuminates adjacent tissue regions on either side of the access. Values of α o  for tissue regions not containing the access are then used to normalize the signal, thus providing a baseline from which relative changes in access hematocrit can be assessed.  
           [0015]    Other objects, features and advantages of the present invention will be apparent to those skilled in the art upon a reading of this specification including the accompanying drawings.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0016]    The invention is better understood by reading the following Detailed Description of the Preferred Embodiments with reference to the accompanying drawing figures, in which like reference numerals refer to like elements throughout, and in which:  
         [0017]    [0017]FIG. 1 is a diagrammatic view of a dialysis circuit in which a TQ a  hematocrit sensor in accordance with the present invention is placed at the hemodialysis vascular access site.  
         [0018]    [0018]FIG. 2 is a perspective view of a first embodiment of a TQ a  hematocrit sensor in accordance with the present invention.  
         [0019]    [0019]FIG. 3 is a bottom plan view of the TQ a  hematocrit sensor of FIG. 2.  
         [0020]    [0020]FIG. 4 is a side elevational view of the TQ a  hematocrit sensor of FIG. 2.  
         [0021]    [0021]FIG. 5 is a top plan view of the TQ a  hematocrit sensor of FIG. 2.  
         [0022]    [0022]FIG. 6 is a cross-sectional view taken along line  6 - 6  of FIG. 2.  
         [0023]    [0023]FIG. 7 is a diagrammatic view illustrating the TQ a  sensor of FIG. 2 and the illuminated volumes or “glowballs” produced by the emitters and seen by the detectors thereof.  
         [0024]    [0024]FIG. 8 is a perspective view of a second embodiment of a TQ a  hematocrit sensor in accordance with the present invention.  
         [0025]    [0025]FIG. 9 is a bottom plan view of the TQ a  hematocrit sensor of FIG. 8.  
         [0026]    [0026]FIG. 10 is a side elevational view of the TQ a  hematocrit sensor of FIG. 8.  
         [0027]    [0027]FIG. 11 is a top plan view of the TQ a  hematocrit sensor of FIG. 8.  
         [0028]    [0028]FIG. 12 is a cross-sectional view taken along line  12 - 12  of FIG. 9.  
         [0029]    [0029]FIG. 13 is a diagrammatic view illustrating the TQ a  hematocrit sensor of FIG. 8 and the illuminated volumes or “glowballs” produced by the emitters and seen by the detector thereof.  
         [0030]    [0030]FIG. 14 is a perspective view of a third embodiment of a TQ a  hematocrit sensor in accordance with the present invention.  
         [0031]    [0031]FIG. 15 is a bottom plan view of the TQ a  hematocrit sensor of FIG. 14.  
         [0032]    [0032]FIG. 16 is a side elevational view of the TQ a  hematocrit sensor of FIG. 14.  
         [0033]    [0033]FIG. 17 is a top plan view of the TQ a  hematocrit sensor of FIG. 14.  
         [0034]    [0034]FIG. 18 is a cross-sectional view taken along line  18 - 18  of FIG. 15.  
         [0035]    [0035]FIG. 19 is a diagrammatic view illustrating the TQ a -hematocrit sensor of FIG. 14 and the illuminated volumes or “glowballs” produced by the emitter and seen by the detectors thereof.  
         [0036]    [0036]FIG. 20 is a perspective view of a fourth embodiment of a TQ a  hematocrit sensor in accordance with the present invention.  
         [0037]    [0037]FIG. 21 is a partial cross-sectional view of the TQ a  hematocrit sensor of FIG. 20.  
         [0038]    [0038]FIG. 22 is a diagrammatic view of the TQ a  hematocrit sensor of FIG. 20 showing the placement of the emitters and detectors relative to the access site.  
         [0039]    FIGS.  23 - 26  are diagrammatic views illustrating the TQ a  hematocrit sensor of FIG. 20 and the illuminated volumes or “glowballs” produced by the emitters and seen by the detectors thereof.  
         [0040]    [0040]FIG. 27 is a perspective view of a fifth embodiment of a TQ a  hematocrit sensor in accordance with the present invention.  
         [0041]    [0041]FIG. 28 is a partial cross-sectional view of the TQ a  hematocrit sensor of FIG. 27.  
         [0042]    [0042]FIG. 29 is a diagrammatic view of the TQ a  hematocrit sensor of FIG. 27 showing the placement of the emitters and detectors relative to the access site.  
         [0043]    FIGS.  30 - 33  are diagrammatic views illustrating the TQ a  hematocrit sensor of FIG. 27 and the illuminated volumes or “glowballs” produced by the emitters and seen by the detectors thereof.  
         [0044]    [0044]FIG. 34 is a cross-sectional view of a TQ a  hematocrit sensor in accordance with the present invention in the form of a disposable adhesive patch.  
         [0045]    [0045]FIG. 35 is a graphical representation of a signal proportional to the hematocrit in the vascular access as recorded by a sensor and associated monitoring system in accordance with the invention.  
         [0046]    [0046]FIG. 36 is a graphical representation of plotted values of the vascular access flow rate determined using a TQ a  sensor in accordance with the present invention versus that determined by a conventional HD 01  monitor.  
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0047]    In describing preferred embodiments of the present invention illustrated in the drawings, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected, and it is to be understood that each specific element includes all technical equivalents that operate in a similar manner to accomplish a similar purpose.  
         [0048]    The following abbreviations and variables are used throughout the present disclosure in connection with the present invention:  
         [0049]    α=access site optical attenuation coefficient  
         [0050]    α o =non-access site optical attenuation coefficient  
         [0051]    B o =composite of all the non-access region S, K coefficients  
         [0052]    C=proportionality scalar  
         [0053]    CPR=cardiopulmonary recirculation  
         [0054]    d=distance between the emitter and the detector  
         [0055]    H=hematocrit, generally  
         [0056]    H a =hematocrit within the vascular access site  
         [0057]    H ao =hematocrit beneath the sensor (outside the dialyzer)  
         [0058]    ΔH=change in hematocrit (H a −H ao )  
         [0059]    i=intensity of light, generally  
         [0060]    I baseline =baseline intensity (taken in the absence of a bolus)  
         [0061]    I measure =light back-scattered from a turbid tissue sample  
         [0062]    I o =emitter radiation intensity  
         [0063]    K=bulk absorption coefficient  
         [0064]    K b =access site blood coefficient  
         [0065]    Q a =vascular access blood flow rate  
         [0066]    Q b =dialyzer blood flow rate  
         [0067]    Q f =dialyzer ultrafiltration rate  
         [0068]    Q i =average injection inflow rate  
         [0069]    S=bulk scattering coefficient  
         [0070]    SD=standard deviation  
         [0071]    SNR=signal-to-noise ratio  
         [0072]    t=time (measured from time of injection)  
         [0073]    TQ a =transcutaneous access blood flow  
         [0074]    V=known volume of saline injected into dialysis venous line  
         [0075]    X b =percentage of the access volume to the total volume illuminated (access blood proration value)  
         [0076]    X o =percentage of the non-access area to the total volume  
         [0077]    The optical hematocrit sensor in accordance with the present invention comprises a light emitting source (emitter) (preferably an LED of specific wavelength) and a complementary photodetector that can be placed directly on the skin over a vascular access site. The LED preferably emits light at a wavelength of 805 nm-880 nm, because it is near the known isobestic wavelength for hemoglobin, is commercially available, and has been shown to be effective in the optical determination of whole blood parameters such as hematocrit and oxygen saturation.  
         [0078]    When the sensor is placed on the surface of the skin, the LED illuminates a volume of tissue, and a small fraction of the light absorbed and back-scattered by the media is detected by the photodetector. While light travels in a straight line, the illuminated volume as seen by the photodetector can be visualized as an isointensity ellipsoid, as individual photons of light are continuously scattered and absorbed by the media. Because a wavelength of 805 nm-880 nm is used, hemoglobin of the blood within the tissue volume is the principal absorbing substance. The scattering and absorbing characteristics are mathematically expressed in terms of a bulk attenuation coefficient (α) that is specific to the illuminated media. The amount of light detected by the photodetector is proportional via a modified Beer&#39;s law formula to the instantaneous net a value of the media.  
         [0079]    When the volume of tissue illuminated includes all or even part of the access, the resultant α o  value includes information about both the surrounding tissue and the access itself. In order to resolve the signal due to blood flowing within the access from that due to the surrounding tissues, the sensor system illuminates adjacent tissue regions on either side of the access. Values of α o  for tissue regions not containing the access are then used to normalize the signal, thus providing a baseline from which relative changes can be assessed in access hematocrit in the access blood flowing directly under the skin.  
         [0080]    [0080]FIG. 1 illustrates a dialysis circuit in which a TQ a  hematocrit sensor  12  in accordance with the present invention is placed over the hemodialysis vascular access site  14 , with the dialysis arterial and venous blood lines  16   a  and  16   b  in the normal configuration, for measuring TQ a . A dialyzer  20  downstream of the vascular access site  14  and a syringe  22  for injecting a reference diluent (for example, saline) downstream of the dialyzer  20  are indicated. The hematocrits and flow rates under steady state conditions are also indicated, where Q a  is the access flow rate, Q b  is the dialyzer blood flow rate, Q i  is the injection flow rate, H a  is the hematocrit in the access flow, and H o  is the hematocrit at the sensor  12 . The hematocrit sensor  12  is placed directly on the skin over the vascular access site  14  downstream of the venous dialysis needle  24 .  
         [0081]    As shown in FIG. 35, the sensor  12  and an associated monitoring system  30  records a signal proportional to the hematocrit in the vascular access site  14  (H a ). The monitoring system  30  can be a computer including a computer processor and memory, and output means such as a video monitor and printer (not shown). After a stable Ha value is obtained, a known volume (V) of normal saline is injected via the syringe  22  into the dialysis venous line  16   b , which reduces the hematocrit beneath the sensor  12  to a time-dependent hematocrit H o  during the injection.  
         [0082]    Derivation of the equation used to calculate the vascular access flow rate when using the bolus injection indicator dilution approach is complex. However, the constant infusion and bolus injection indicator dilution approaches yield identical results; therefore, the governing equation was derived from steady state constant infusion principles. Consider the dialysis circuit in FIG. 1 where a steady infusion of saline occurs in the dialysis venous blood line  16   b  (ultrafiltration at the dialyzer  20  is neglected). Red cell balance where the dialysis venous blood flow enters the access site  14  requires  
           H   a ( Q   a   −Q   b )+ H   a   Q   b   =H   o ( Q   a   +Q   i )  (1)  
         [0083]    Solving for Q a , the vascular access flow rate, yields  
               Q   a     =       Q   i         Δ                 H       H   o                 (   2   )                               
 
         [0084]    where ΔH denotes H a −H ao . This equation describes the changes in hematocrit at the sensor  12  during a constant infusion of normal saline in the dialysis venous blood line  16   b . (If ultrafiltration at the dialyzer  20  occurs at a rate of Q f , then the numerator in this equation becomes Q i −Q f ).  
         [0085]    Noting that Q i  is equivalent to the volume of saline injected in a specified time interval, equation (2) is therefore equivalent to:  
               Q   a     =     V     ∫       F        (       Δ                 H     H     )            (   t   )             t                   (   3   )                               
 
         [0086]    to yield the vascular access flow rate (Q a ), where ΔH denotes H a −H ao  and the integral (area under the curve) in the above equation is from the time of injection (t=0) to where the signal has returned to the baseline value (t=∞). This equation is valid independent of the rate of saline injection or the dialyzer blood flow rate. The signals detected by the TQ a  sensor  12  can be used to calculate  
         F        (       Δ                 H       H   o       )       .                         
 
         [0087]    Determination  
       fF        (       Δ                 H     H     )                           
 
         [0088]    The percentage change in blood parameters (both macroscopic and microscopic) passing through the access site  14  may be measured in a variety of ways. Macroscopic parameters such as bulk density or flow energy can be measured by ultrasonic, temperature, or conductivity means. Microscopic parameters (sometimes called “physiologic or intrinsic” parameters) such as hematocrit or red cell oxygen content are measured by optical means. Each technique has its respective advantages and disadvantages, both rely on the quantity  
           Δ                 H     H     .                         
 
         [0089]    Inherent in all of these is the need to differentiate the access site  14 , and parameter changes therein, from the surrounding tissue structure. The TQ a  sensor  12  in accordance with the present invention is positioned directly over the access site region  14  itself approximately 25 mm downstream of the venous needle  24 , and is based upon optical back-scattering of monochromatic light (λ=805 nm−880 nm) from the blood flow in the access site  14  and the surrounding tissues. The theory on which the construction of the TQ a  sensor  12  is based requires the use of optical physics and laws associated with optical determination of physiologic elements including hematocrit.  
         [0090]    Modified Beer&#39;s Law  
         [0091]    Numerous studies have shown that light back-scattered from a turbid tissue sample follows a modified form of Beer&#39;s Law,  
           I   measured   =I   o   Ae   −ad   (4)  
         [0092]    where I o  is the radiation intensity emitted from the LED, A is a complex function of d and α of the various layers of tissue (epidermis, dermis, and subcutaneous tissue), d is the distance between the LED and detector, and a is the bulk optical attenuation coefficient. The α term is a function of the absorption and scattering nature of the tissue and has a strong dependence on hematocrit.  
             α   ≈         -   L                   n                   (       I   measured       I   o       )       d             (   5   )                               
 
         [0093]    Compartmentalization of α 
         [0094]    A transcutaneously measured a value is actually a prorated composite measure of all the absorption and scattering elements contained within the illuminated volume or “glowball” of the emitter source, and typically includes the effects of tissue, water, bone, blood, and in the case of hemodialysis patients, the access site  14 . In the determination of a, clearly only the blood flowing through the access site  14  is of interest. The task therefore becomes one of separating the effects of absorption and scattering of the access site  14  from that of surrounding tissue structure. Starting with the well known definition,  
         α={square root}{square root over (3 K ( K+S ))}  (6)  
         [0095]    where K is the bulk absorption coefficient and S is the bulk scattering coefficient, and separating the access site  14  from non-access blood coefficients and rearranging terms,  
           X   b   K   b ≈α 2   −B   o   (7)  
         [0096]    where  
         [0097]    X b =ratio of the access volume to the total volume illuminated  
         [0098]    K b =access blood coefficient  
         [0099]    B o =composite of all the non-access region S and K coefficients  
         [0100]    Now, letting the non-access components become α o   2 =B o , we have  
           X   b   K   b   =X   b   =α   2 −α o   2   (8)  
         [0101]    In equation (6), the access blood coefficient, K b , is directly proportional to hematocrit (H), K b =H·C. Therefore,  
           X   b   K   b   =X   b   ·H·C=α   2 −α o   2   (9)  
         [0102]    where C is a proportionality scalar known from the literature or empirically derived.  
         [0103]    To determine α o , measurements are made in areas  130   b  and  130   c  near but not including the access site  14 , as depicted, for example, in FIG. 7. If the tissue is more or less homogenous, it is only necessary to make a single reference α o  measurement, using either two emitters  202   a  and  202   b  and one detector  204  (as shown in FIG. 13) or one emitter  302  and two detectors  304   a  and  304   b  (as shown in FIG. 19), as discussed in greater detail hereinafter. On the other hand, if a gradient in α o  exists in the area of interest (and this is often the case in vivo) multiple measurements are made to establish the nature of the gradient and provide an averaged estimate of α o , using two emitters  102   a  and  102   b  and two detectors  104   a  and  104   b , as discussed in greater detail hereinafter in connection with FIGS.  2 - 6 .  
         [0104]    Determination of  
       di   i                         
 
         [0105]    The value of  
       di   i                         
 
         [0106]    is defined as the time derivative of intensity i, normalized by i. This is expressed as  
                   di   i     =             X   b     ·   Δ                     K   b       α          (     d   -     1   α       )         ,       where                 A     ≈   α     ,     from                   equation                             (   4   )              
          or   ,     
                X   b     ·   Δ                     K   b       =           d   i     i        α       (     d   -     1   α       )                   (   10   )                               
 
         [0107]    wherein ΔK b  is proportional to ΔH. Hence,  
                   X   b     ·   Δ                     H   ·   C       =           X   b     ·   Δ                     K   b       =           d   i     i        α       (     d   -     1   α       )                 (   11   )                               
 
         [0108]    To determine  
           d                 i     i     ,                         
 
         [0109]    a baseline intensity (taken in the absence of a bolus) is first measured to establish a reference. The intensity is then measured as a time varying signal as the saline bolus is injected, I(t). The quantity  
         d                 i     i                         
 
         [0110]    is then calculated as  
                 d                 i     i     =         I   baseline     -     I        (   t   )           I   baseline               (   12   )                               
 
         [0111]    Final Determination of  
       F        (       Δ                 H     H     )                           
 
         [0112]    The value  
       F        (       Δ                 H     H     )                           
 
         [0113]    is the ratio of equations (11) and (8),  
               F        (       Δ                 H     H     )       =             d                 i     i        α         (     d   -     1   α       )          (       α   2     -     α   o   2       )         .             (   13   )                               
 
         [0114]    Since d is fixed and known  
           d                 i     i     ,                         
 
         [0115]    α, and α o  are computed by equations (10) and (5). It is important to note that in the final ratio of  
         F        (       Δ                 H     H     )       ,                         
 
         [0116]    the access blood proration value, X b , cancels out. This removes vascular access size, volume, or depth dependence from the final result. Likewise, the  
         d                 i     i                         
 
         [0117]    and  
       α       α   2     -     α   o   2                             
 
         [0118]    ratios eliminate skin color variations.  
         [0119]    In order to use indicator dilution techniques to measure vascular access flow rates during routine hemodialysis, the indicator must be injected upstream and its concentration detected downstream in the blood flowing through the vascular access site  14 . Reversing the dialysis blood lines  16   a  and  16   b  during the hemodialysis treatment permits application of indicator dilution by direct injection of the indicator into the dialysis venous tubing  16   b . Because the TQ a  sensor  12  can detect a dilution signal downstream of the venous needle  24  through the skin, a unique application of indicator dilution principles permits determination of the vascular access flow rate without reversal of the dialysis blood lines  16   a  and  16   b . Various methods of measuring vascular access blood flow rate, as well as a method for locating accesses and grafts and localizing veins in normal patients, using the TQ a  sensor  12  are described in co-pending application entitled “Method of Measuring Transcutaneous Access Blood Flow,” filed on even date herewith, Attorney Docket P65685US0, which is incorporated herein in its entirety.  
         [0120]    The accuracy of the measurements taken using the TQ a  sensor  12  depends critically on at least two factors. As can be seen in equation (3) above, the calculated access flow rate depends directly on the volume of saline injected; therefore, care must be taken to inject a given amount of saline over a specified time interval. The latter does not need to be known precisely; however, it is important that it be less than approximately 10 seconds to avoid significant interference due to cardiopulmonary recirculation (CPR) of the injected saline. The second factor that is important to consider in the accuracy of the TQ a  measurements is the placement of the TQ a  sensor  12  to accurately determine changes in hematocrit through the skin. The sensor  12  must be placed directly over the vascular access site  14  approximately 25 mm downstream of the venous needle  24  in the specified orientation to accurately determine the relative changes in hematocrit. Additional variability due to sensor placement does not appear, however, to be significant, in that small variations in sensor placement do not significantly influence the measured vascular access flow rate. An additional concern is whether variations in accuracy of measurements taken using the TQ a  sensor  12  may occur with access sites that are not superficial or if the access diameter is very large; however, varying the spacing of sensor elements eliminates difficulties associated with very large accesses or with deeper access sites such as those typically found in the upper arm or thigh. Less accurate results would also be obtained if the sensor  12  does not accurately detect changes in hematocrit due to significant variation in skin pigmentation. The TQ a  sensor in accordance with the invention has been specifically designed to account for the individual absorption and scattering properties of patient tissues, through the use of 805 nm-880 nm LED optical technology, and the normalized nature of the measurements  
       (     di   i     )                         
 
         [0121]    suggests that the sensitivity of the calculated vascular access flow rate to skin melanin content is minimal.  
         [0122]    Referring now to FIGS.  2 - 6 , there is shown a first embodiment of the TQ a  sensor  100  in accordance with the present invention for the transcutaneous measurement of vascular access blood flow in a hemodialysis shunt or fistula  14 . In this embodiment two emitters  102   a  and  102   b  and two detectors  104   a  and  104   b  are arranged in alignment along an axis A 1  on a substrate  110 . As mentioned above, this embodiment is employed if a gradient in α o  exists in the area of interest (as is often the case in vivo), as multiple measurements must be made to establish the nature of the gradient and provide an averaged estimate of α o .  
         [0123]    The sensor  100  has an access placement line L 1  perpendicular to the axis A 1 . For proper operation, the sensor  100  must be placed with the access placement line L 1  over the venous access site (shunt)  14 . One of the emitters (the “inboard emitter”)  102   a  and one of the detectors (the “inboard detector”)  104   a  are placed at inboard positions on either side of and equidistant from the access placement line L 1 . The second emitter (the “outboard emitter”)  102   b  is placed at a position outboard of the inboard detector  104   a , while the second detector (the “outboard detector”)  104   b  is placed at a position outboard of the inboard emitter  102   a , so that the emitters  102   a  and  102   b  and detectors  104   a  and  104   b  alternate. The spacing between the emitters  102   a  and  102   b  and the detectors  104   a  and  104   b  is uniform.  
         [0124]    The substrate  110  is provided with apertures  116  in its lower surface (the surface which in use faces the access site  20 ) for receiving the emitters  102   a  and  102   b  and the detectors  104   a  and  104   b . The apertures  116  are sized so that the emitters  102   a  and  102   b  and the detectors  104   a  and  104   b  lie flush with the lower surface of the substrate  110 .  
         [0125]    Preferably, the upper surface of the substrate  110  is marked with the access placement line L 1 . The upper surface of the substrate  110  may also be provided with small projections  120  or other markings above the apertures  116  indicating the locations of the emitters  102   a  and  102   b  and the detectors  104   a  and  104   b.    
         [0126]    The circuitry (not shown) associated with the emitters  102   a  and  102   b  and the detectors  104   a  and  104   b  can be provided as a printed circuit on the lower surface of the substrate  110 . The substrate  110  is made of a material that is flexible enough to conform to the contours of the underlying tissue but rigid enough to have body durability.  
         [0127]    As shown in FIG. 7, there are three illuminated volumes or “glowballs”  130   a ,  130   b , and  130   c  in the tissue, T, seen by the two detectors  104   a  and  104   b : a first glowball  130   a  representing the reflective penetration volume (α) of the inboard emitter  102   a  through the access site tissue as seen by the inboard detector  104   a  in the process of determination of the access Hematocrit; a second glowball  130   b  representing the reflective penetration (α o1 ) of the inboard emitter  102   a  through the non-access site tissue that surrounds the access site  14  as seen by the outboard detector  104   b ; and a third glowball  130   c  representing the reflective penetration (α o2 ) of the outboard emitter  102   b  through the non-access site tissue that surrounds the access site  14  as seen by the inboard detector  104   a . An estimate of α o  is made by averaging α o1  and α o2 . That is,  
               α   o     =         α   o1     +     α   o2       2             (   14   )                               
 
         [0128]    Due to the depth of the access site  14 , in order for the cross-section of the access site  14  to be enclosed by the glowball  130   a  of the inboard emitter  102   a  seen by the inboard detector  104   a , the spacing between the inboard and outboard detectors  104   a  and  104   b  is typically 24 mm.  
         [0129]    Referring now to FIGS.  8 - 12 , there is shown a second embodiment of the TQ a  sensor  200  in accordance with the present invention. In this embodiment two emitters  202   a  and  202   b  and one detector  204  are arranged in alignment along an axis A 2  on a substrate  210 . As mentioned above, this embodiment is employed if the tissue, T, is more or less homogenous, and it is only necessary to make a single reference a o  measurement.  
         [0130]    The sensor  200  has an access placement line L 2  perpendicular to the axis A 2 . One of the emitters (the “inboard emitter”)  202   a  and the detector  204  are placed at inboard positions on either side of and equidistant from the access placement line L 2 . The second emitter (the “outboard emitter”)  202   b  is placed at a position outboard of the detector  204 , so that the emitters  202   a  and  202   b  and the detector  204  alternate. The spacing between the emitters  202   a  and  202   b  and the detector  204  is uniform.  
         [0131]    The substrate  210  is provided with apertures  216  in its lower surface for receiving the emitters  202   a  and  202   b  and the detector  204 . The apertures  216  are sized so that the emitters  202   a  and  202   b  and the detector  204  lie flush with the lower surface of the substrate  210 .  
         [0132]    Preferably, the upper surface of the substrate  210  is marked with the access placement line L 2 , and also is marked with “plus” and “minus” signs  218   a  and  218   b , which indicate the direction to move the sensor  200  left or right. The upper surface of the substrate  210  may also be provided with small projections  220  or other markings above the apertures  216  indicating the locations of the emitters  202   a  and  202   b  and the detector  204 .  
         [0133]    The circuitry (not shown) associated with the emitters  202   a  and  202   b  and the detector  204  can be provided as a printed circuit on the lower surface of the substrate  210 . The substrate  210  is made of a material that is flexible enough to conform to the contours of the underlying tissue but rigid enough to have body durability.  
         [0134]    As shown in FIG. 13, there are two illuminated “glowballs”  230   a  and  230   b  seen by the single detector  204 : a first glowball  230   a  representing the reflective penetration (α) of the inboard emitter  202   a  through the access site tissue as seen by the single detector  204  in the process of determination of the access Hematocrit; and a second glowball  230   b  representing the reflective penetration (α o ) of the outboard emitter  202   b  through the non-access site tissue that surrounds the access site  14  as seen by the single detector  204 .  
         [0135]    Referring now to FIGS.  14 - 18 , there is shown a third embodiment of the TQ a  sensor  300  in accordance with the present invention. The third embodiment is similar to the second embodiment, except that one emitter  302  and two detector  304   a  and  304   b  are arranged in alignment along an axis A 3  on a substrate  310 .  
         [0136]    The sensor  300  has an access placement line L 3  perpendicular to the axis A 3 . The emitter  302  and one of the detectors (the “inboard detector”)  304   a  are placed at inboard positions on either side of and equidistant from the access placement line L 3 . The second detector (the “outboard detector”)  304   b  is placed at a position outboard of the emitter  302 , so that the emitter  302  and the detectors  304   a  and  304   b  alternate. The spacing between the emitter  302  and the detectors  304   a  and  304   b  is uniform.  
         [0137]    The substrate  310  is provided with apertures  316  in its lower surface for receiving the emitter  302  and the detectors  3204   a  and  3204   b . The apertures  316  are sized so that the emitter  302  and the detectors  304   a  and  304   b  lie flush with the lower surface of the substrate  210 .  
         [0138]    The circuitry (not shown) associated with the emitter  302  and the detectors  304   a  and  304   b  can be provided as a printed circuit on the lower surface of the substrate  310 . The substrate  310  is made of a material that is flexible enough to conform to the contours of the underlying tissue but rigid enough to have body durability.  
         [0139]    Preferably, the upper surface of the substrate  310  is marked with the access placement line L 3 , and also is marked with “plus” and “minus” signs  318   a  and  318   b , which indicate the direction to move the sensor  300  left or right. The upper surface of the substrate  310  may also be provided with small projections  320  or other markings above the apertures  316  indicating the locations of the emitter  302  and the detectors  304   a  and  304   b.    
         [0140]    As shown in FIG. 19, there are two illuminated “glowballs”  330   a  and  330   b  seen by the detectors  304   a  and  304   b : a first glowball  330   a  representing the reflective penetration (a) of the single emitter  302  through the access tissue as seen by the inboard detector  304   a  in the process of determination of the access Hematocrit; and a second glowball  330   b  representing the reflective penetration (α o ) of the single emitter  302  through the non-access site tissue that surrounds the access site  14  as seen by the outboard detector  304   b  In the first three embodiments, the placement of the emitters and detectors permits all of the measurements to be made only in tissue volumes perpendicular to the access site  14 . There will now be discussed fourth and fifth embodiments, in which the placement of the emitters and detectors permits measurements to be made in tissue areas parallel, as well as perpendicular, to the access site  14 .  
         [0141]    Referring to FIGS.  20 - 22 , there is shown a fourth embodiment of the TQ a  sensor  400  in accordance with the present invention. In the fourth embodiment, a flexible components layer  410  is provided having an access placement line L 4 . An upstream and a downstream emitter  402   a  and  402   b  are arranged on the components layer  410  along a first diagonal line D 1  forming a 45° angle with the access placement line L 4 , and an upstream and a downstream detector  404   a  and  404   b  are arranged along a second line D 2  perpendicular to the first line at its point of intersection P with the access placement line L 4 . The upstream and downstream emitters  402   a  and  402   b  and the upstream and downstream detectors  404   a  and  404   b  are equidistant from the point of intersection P. It will thus be seen that the upstream emitter  402   a  and the downstream detector  404   b  lie on one side of the access placement line L 4  along a line parallel thereto, and the upstream detector  404   a  and the downstream emitter  402   b  lie on the other side of the access placement line LA along a line parallel thereto; and that the upstream emitter  402   a  and the upstream detector  404   a  lie along a line perpendicular to the access placement line L 4 , as do the downstream emitter  402   b  and the downstream detector  404   b.    
         [0142]    In the TQ a  sensor  400  in accordance with the fourth embodiment, the circuitry associated with the emitters  402   a  and  402   b  and the detectors  404   a  and  404   b  is also incorporated in the flexible components layer  410 . The components layer  410  has a lower surface that faces the access site  14 , and an upper surface that faces away. The emitters  402   a  and  402   b  and the detectors  404   a  and  404   b  may protrude from the lower surface of the components layer  410 . A cover layer  412  of flexible foam or the like covers the upper surface of the components layer  410 . A spacer layer  414  of flexible foam or the like covers the lower surface of the components layer  410 , and has apertures  416  in registration with the emitters  402   a  and  402   b  and the detectors  404   a  and  404   b , so that each emitter and detector is received in its own corresponding aperture  416 . The spacer layer  414  has an upper surface that contacts the lower surface of the components layer  410  and a lower surface that faces away from the components layer  410 .  
         [0143]    Preferably, the upper surface of the cover layer  412  is marked with the access placement line L 4 , and also is marked to indicate which end of the access placement line L 4  is to be placed adjacent the venous needle  24 , to assist in proper placement. Also, the TQ a  sensor  400  preferably is elongated in the direction of the access placement line L 4 , in order to ensure the proper placement of the emitters  402   a  and  402   b  and the detectors  404   a  and  404   b  relative to the venous needle  24 .  
         [0144]    In order to hold the TQ a  sensor  400  in place, a transparent adhesive layer  420  can be applied to the lower surface of the spacer layer  414 . The adhesive can be any suitable pressure sensitive adhesive. A release liner  422  covers the adhesive layer  420 . Prior to use, the release layer  424  is removed from the adhesive layer  420  of the TQ a  sensor  400 , and the TQ a  sensor  400  is adhered to the access site  14 .  
         [0145]    As shown in FIGS.  23 - 26 , there are four illuminated “glowballs” seen by the upstream and downstream detectors: a first glowball  430   a  representing the reflective penetration (a) of the upstream emitter  402   a  through the access site tissue as seen by the upstream detector  404   a  in the process of determination of the access hematocrit (FIG. 23); a second glowball  430   b  representing the reflective penetration (a) of the downstream emitter  402   b  through the access site tissue as seen by the downstream detector  404   b  in the process of determination of the access Hematocrit (FIG. 24); a third glowball  430   c  representing the reflective penetration (α o1 ) of the upstream emitter  402   a  through the non-access site tissue that surrounds the access site  14  as seen by the downstream detector  404   b  (FIG. 25); and a fourth glowball  430   d  representing the reflective penetration (α o2 ) of the downstream emitter  404   b  through the non-access site tissue that surrounds the access site  14  as seen by the upstream detector  404   a  (FIG. 26). An estimate of α o  is again made by averaging α o1  and α o2 .  
         [0146]    Referring to FIGS.  27 - 29 , there is shown a fifth embodiment of the TQ a  sensor  500  in accordance with the present invention. In the fifth embodiment, a substrate  510  is provided having an access placement line L 5 . A first upstream emitter  502   a  and a downstream emitter  502   b  are arranged on the substrate  510  along a first diagonal line D 3  forming a 45° angle with the access placement line L 5 , and upstream and downstream detectors  504   a  and  504   b  are arranged along a second line D 4  perpendicular to the first line at its point of intersection P with the access placement line L 4 , exactly as in the fourth embodiment, with the first upstream and the downstream emitters  502   a  and  502   b  and the upstream and downstream detectors  504   a  and  504   b  being equidistant from the point of intersection P. In addition, the second, third, fourth, fifth, and sixth upstream detectors  502   c ,  502   d ,  502   e ,  502   f , and  502   g  are arranged in alignment along a line defined by the first upstream emitter  502   a  and the upstream detector  504   a , with the fourth detector  502   e  lying on the access placement line L 5 . The second, third, fourth, fifth, and sixth emitters  502   c ,  502   d ,  502   e ,  502   f , and  502   g  are uniformly spaced between the first upstream emitter  502   a  and the upstream detector  504   a  and can be used to locate the access. In addition, pairs of emitters  502   a  and  502   c - 502   g  can be used to determine the diameter of the access.  
         [0147]    The cover layer  512 , spacer layer  514 , adhesive layer  522 , and release liner  524  of the sensor  500  in accordance with the fifth embodiment are identical to those of the sensor  400  of the fourth embodiment, except that the apertures  516  in the spacer layer  514  will be placed in accordance with the placement of the emitters  502   a - 502   g  and the detectors  504   a  and  504   b  in the components layer  510  of the fifth embodiment.  
         [0148]    As shown in FIGS. 30 and 31, there are six illuminated glowballs perpendicular to the access site  14  and one illuminated glowball parallel to the access site  14  that are seen by the upstream detector  504   a : a first glowball  530   a  representing the reflective penetration (α) of the first upstream emitter  502   a  through the access site tissue in the process of determination of the access site Hematocrit (FIG. 30); a second glowball  530   b  representing the reflective penetration (α o1 ) of the downstream emitter  502   b  through the non-access site tissue that is parallel to the access site  14  (FIG. 31); a third glowball  530   c  representing the reflective penetration of the second upstream emitter  502   c  through both non-access and some of the access volume (FIG. 30); a fourth glowball  530   d  representing the reflective penetration of the third upstream emitter  502   d  through both non-access and some of the access volume (FIG. 30); a fifth glowball  530   e  representing the reflective penetration of the fourth upstream emitter  502   e  through both non-access and some of the access volume (FIG. 30); a sixth glowball  530   f  representing the reflective penetration of the fifth upstream emitter  502   f  through non-access the access volume (FIG. 30); and a seventh glowball  530   g  representing the reflective penetration of the sixth upstream emitter  502   g  through non-access volume (FIG. 30).  
         [0149]    As shown in FIGS. 32 and 33, there are two illuminated “glowballs” seen by the downstream detector  504   b : an eighth glowball  530   h  representing the reflective-penetration (α o2 ) of the first upstream emitter  502   a  through the non-access site tissue that is parallel to the access site  14  (FIG. 32); and a second glowball  530   i  representing the reflective penetration (a) of the downstream emitter  502   b  through the access site tissue in the process of determination of the access Hematocrit (FIG. 33). An estimate of α o  is made by averaging α o1  and α o2 , and then using equation (13) to determine  
         F        (       Δ                 H     H     )       .                         
 
         [0150]    Due to the depth of the access site  14 , in order for the cross-section of the access site  14  to be enclosed by the glowball of the first upstream emitter  502   a  seen by the upstream detector  504   a , the spacing between the first upstream emitter  502   a  and the upstream detector  504   a  is typically 24 mm. The remaining upstream emitters  502   c - 502   g  are equally spaced between the first upstream emitter  502   a  and the upstream detector  504   a . Similarly, the spacing between the downstream emitter  502   b  and the downstream detector  504   b  are typically 24 mm.  
         [0151]    As indicated above, in all of the embodiments, the emitters are preferably LEDs that emit light at a wavelength of 805 nm-880 nm, and the detectors are silicon photodiodes. In the first three embodiments shown in FIGS.  2 - 6 ,  8 - 12 , and  14 - 18 , the substrate preferably is provided with an exterior covering (see FIG. 34) of a plastic material, for example urethane or silicone, and the emitters and detectors lie flush with the lower surface of the exterior covering, that is, the surface that faces the skin, so that the emitters and detectors lie on the skin. In the fourth and fifth embodiments shown in FIGS.  20 - 22  and  27 - 29 , each emitter and detector is recessed in an aperture. The fourth and fifth embodiments use more LED&#39;s than the other embodiments.  
         [0152]    Also in all of the embodiments, an emitter-detector separation is required so that the reflectance of the first layer of tissue (a non-blood layer of epithelium) does not further exaggerate a multiple scattering effect, as discussed in U.S. Pat. No. 5,499,627, which is incorporated herein by reference in its entirety.  
         [0153]    Further, in the all of the embodiments, the distance between each adjacent pair of emitters and detectors must be sufficient for a portion of the access site  14  to be enclosed within the illuminated volume or “glowball” of the inboard emitter. This distance typically is about 24 mm, except as described above with respect to the fifth embodiment.  
         [0154]    Finally, in all of the embodiments, the sensor can be fastened in place using surgical tape. Alternatively, any of the embodiments can be made as a disposable adhesive patch that cannot be recalibrated and used again. Referring to FIG. 34, a sensor  600  includes a substrate  610  that houses a plurality of emitters and detectors (not shown) as previously described, a circuit  652  printed on the skin side of the substrate  610 , and an exterior covering  654  covering the circuit  652  and the exposed sides of the substrate  610 . The substrate  610  can comprise a flexible material such as MYLAR on which conductive paint has been deposited to define a circuit. Apertures  656  are formed through the skin side of the exterior covering  654  in registration with circuit junctions that are covered by conductive paint that allows continuity across the junctions. Plugs  660  are inserted into the apertures  656  in such a fashion that they adhere to the conductive paint at the circuit junctions. The skin side of the exterior covering  654  is covered by a removable protective layer  662 , to which the plugs  660  are also affixed.  
         [0155]    Following removal of the sensor  600  from its sterile package and pre-use test and calibration, the protective surface protective layer  662  must be removed in order for the sensor  600  to take a measurement. Because the plugs  660  are adhered to the protective layer  662 , when the protective layer  662  is peeled off, the plugs  660  are pulled out of their apertures  656  along with the conductive paint covering the circuit junctions. The circuitry is designed such that once the circuit is broken, the sensor  600  cannot be calibrated again, and can only be used to take one measurement. The sensor  600  thus cannot be re-used.  
         [0156]    Operability of the TQ a  sensor in accordance with the invention was confirmed in in vivo tests in 59 hemodialysis patients. Prior to the study dialysis session, a disposable tubing with an injection port (CO-daptoR, Transonic Systems, Ithaca, N.Y., USA) was placed between the venous dialysis tubing and the venous needle. The dialysis circuit was primed with saline in usual fashion taking extra care to remove any air bubbles from the venous injection port.  
         [0157]    Within the first hour of dialysis, access recirculation was first measured by the HD 01  monitor (Transonic Systems). Then, the dialyzer blood pump was stopped, the dialysis lines were reversed from their normal configuration, and the access blood flow rate was determined, in duplicate, by the HD 01  monitor (Transonic Systems). Injection of saline was performed using the saline release method (abstract: Krivitski et al, J Am Soc Nephrol 8:164A,  1997 ). The dialyzer blood pump was again stopped and the dialysis lines were returned to their normal configuration.  
         [0158]    After the dialysis blood lines were returned to the normal configuration and the dialyzer blood pump was restarted, the transcutaneous hematocrit sensor was placed on the skin over the patient&#39;s vascular access approximately 25 mm downstream of the venous needle. Thirty ml of normal saline solution were then injected into the injection port of the disposable tubing adjacent to the venous needle at a rate of approximately 300 nm/min to determine access blood flow rate using the TQ a  sensor of the invention. In six patients, saline was injected directly into the arterial dialysis needle before connecting the needle to the complete dialysis circuit. In two patients, saline was injected directly into the access by using a needle and syringe. The data from these various methods were combined together, independent of where saline was injected into the access. The resulting  
       F        (       Δ                 H     H     )                           
 
         [0159]    signal proportional to  
         Δ                 H     H                         
 
         [0160]    is shown in FIG. 35 with the saline bolus. In  38  patients, this measurement was performed in duplicate to assess the replicability of the method.  
         [0161]    All measured and calculated values are reported as mean±SD. The significance of differences in calculated vascular access flow rates determined using the TQ a  sensor and those determined by the HD 01  monitor was determined using a paired Student&#39;s t-test. The variability of the slope and intercept from the regression equation is expressed as ± the estimated SD (or the SE). The results from the replicability and reproducibility studies are expressed as the average coefficient of variation for the duplicate measurements. P values less than 0.05 were considered statistically significant.  
         [0162]    The patients studied were predominantly male and Caucasian; 5 Black and 1 Native American patients were studied. Although the distribution of patient race in the study was not representative of that within the United States as a whole, it was representative of the population in the geographical region where the test was conducted. The age of the patients, the fraction of diabetic patients and the fraction of patients with synthetic PTFE grafts were similar to those for chronic hemodialysis patients in the United States. Eleven patients were studied twice and one patient was studied three times. All other patients were studied once for a total of 72 measurements. Access recirculation was significant in three patients. In those patients, the blood pump setting was reduced to 150 ml/min to eliminate access recirculation before completing the study protocol.  
         [0163]    [0163]FIG. 36 shows values of the vascular access flow rate determined using the TQ a  sensor plotted versus that determined by the HD 01  monitor. The best-fit linear regression line has a slope of essentially unity and a small y-intercept. There was no significant difference between vascular access flow rates determined using the TQ a  sensor and those determined by the HD 01  monitor; the mean absolute difference between these methods was 71±63 ml/min. When these results were analyzed for various patient subgroups (male vs. female, black vs. white, diabetic vs. nondiabetic, synthetic grafts vs. native fistulas), excellent agreement between the measured access blood flow rates was similarly observed.  
         [0164]    Because the optical TQ a  sensor in accordance with the invention can accurately determine instantaneous changes in hematocrit, it permits use of the bolus injection indicator dilution approach (Henriques-Hamilton-Bergner Principle). This optical approach is likely to be of considerable interest to nephrologists since it is also possible to determine the vascular access flow rate when the patient is in the physician&#39;s office or in the clinic and not being treated by hemodialysis by simply injecting saline directly into the access and measuring with a downstream TQ a  sensor. During the initial study, eight patients had vascular access flow rate determinations by direct injection of saline into the access prior to dialysis; their results were later confirmed once the dialysis circuit was in place and functioning. Furthermore, two additional studies were perfored excusively by injecting saline into the access, with excellent results. Thus, it may now be possible to use the TQ a  sensor in accordance with the invention to regularly monitor the vascular access flow rate as an indicator of access function when the patient is not being dialyzed, as well as during maturation of native fistulas prior to first use.  
         [0165]    Modifications and variations of the above-described embodiments of the present invention are possible, as appreciated by those skilled in the art in light of the above teachings. For example, the sensor in accordance with the present invention can be used to measure blood constituents other than hematocrit, such as albumen and glucose, in which case the LEDs emit different wavelengths suited to the specific constituent.  
         [0166]    Further, the detector-emitter arrangement of the sensor in accordance with the present invention, and in particular of the sensor  110  shown in FIG. 7, allows for precise access location, as a “flow finder,” and also can be used to locate grafts and to localize veins in normal patients for more efficient canulatization. In this connection, the sensor  110  is placed directly on the skin over the approximate area of the access, graft, or vein, and values of α, α 1 , and α 2  are calculated as described above. A reference ratio, RR, is developed, where:  
       RR   =       (     1   -       α   o1       α   02         )     ×   100                           
 
         [0167]    When RR&lt;±15, then the access or graft or vein is “centered” correctly or found between the inboard LED  102   a  and the inboard detector  104   a . Also, a signal strength (SS) indicator advises the user whether a sufficient signal is present for an accurate measurement, where  
       SS   =     [       (     α   -     (         α   o1     +     α   o2       2     )       ]     ×   100                             
 
         [0168]    When SS&gt;40, then a sufficient amount of the access or graft or vein is within the illuminated volume of tissue. If RR is not &lt;+15 (that is, if RR≧2±15), or if SS is not &gt;40 (that is, if SS is &lt;40), then the sensor  110  is moved right or left (+ or −) to find the appropriate spot or location.  
         [0169]    It is therefore to be understood that, within the scope of the appended claims and their equivalents, the invention may be practiced otherwise than as specifically described.