Abstract:
Non-invasive spectrophotometric monitoring of oxygen saturation levels based on a combination of continuous wave spectrophotometry (CWS) and phase modulation spectrophotometry (PMS) is described. First information representative of absolute oxygen saturation levels in relatively shallow regions of a patient tissue volume are acquired from PMS-based monitoring thereof during a reference interval. Second information representative of non-absolute oxygen saturation levels in relatively deep regions of the tissue volume are acquired from CWS-based monitoring thereof during the reference interval. Based on the first and second information acquired during the reference interval, a mapping is automatically determined between the second information and estimated absolute oxygen saturation metrics for the relatively deep regions. On a continuing basis during a monitoring interval subsequent to the reference interval, the second information continuously acquired from CWS-based monitoring of the tissue volume are continuously mapped into estimated absolute oxygen saturation metrics, which are continuously displayed on a display output.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This patent application claims the benefit of U.S. Provisional Ser. No. 61/150,017, filed Feb. 5, 2009, which is incorporated by reference herein. 
     
    
     FIELD 
       [0002]    This patent specification relates to the monitoring of a physiological condition of a patient using information from near-infrared (NIR) optical scans. More particularly, this patent specification relates to the monitoring of tissue oxygenation based on a combination continuous wave spectrophotometry (CWS) and phase-modulation spectrophotometry (PMS). 
       BACKGROUND AND SUMMARY 
       [0003]    The use of near-infrared (NIR) light as a basis for the measurement of biological properties or conditions in living tissue is particularly appealing because of its relative safety as compared, for example, to the use of ionizing radiation. Various techniques have been proposed for non-invasive NIR spectroscopy or NIR spectrophotometry (NIRS) of biological tissue. Generally speaking, these techniques are directed to detecting the concentrations of one or more chromophores in the biological tissue, such as blood hemoglobin in oxygenated (HbO) and deoxygenated (Hb) states. 
         [0004]    As used herein, NIR tissue oxygenation level monitoring refers to the introduction of NIR radiation (e.g., in the 500-2000 nm range) into a tissue volume and the processing of received NIR radiation migrating outward from the tissue volume to generate at least one metric indicative of oxygenation level(s) in the tissue. One example of an oxygenation level metric is oxygen saturation, denoted herein by the symbol SO 2 , which refers to the fraction or percentage of total hemoglobin in the tissue volume that is oxygenated hemoglobin. An NIR-based oxygen saturation reading can be classified as “absolute” or “non-absolute” in nature. An absolute SO 2  reading refers to an actual quantitative percentage of the total hemoglobin that is oxygenated hemoglobin for the tissue volume of interest. In contrast, a non-absolute SO 2  reading, which can alternatively be termed a “relative” or “trend-only” reading, refers to a measurement that cannot or should not be tied to such an actual quantitative percentage. By way of analogy, absolute SO 2  readings can be likened to an auto speedometer having a dial that is specifically printed with miles per hour or kilometers per hour numbers on it, whereas non-absolute SO 2  readings can be likened to an auto speedometer having a dial with no numbers printed on it, or that alternatively has an arbitrary scale of numbers printed on it. 
         [0005]    NIR cerebral oxygenation level monitoring, which refers to the transcranial introduction of NIR radiation into the intracranial compartment and the processing of received NIR radiation migrating outward therefrom to generate at least one metric indicative of oxygenation level(s) in the brain, represents one particularly important type NIR tissue oxygenation level monitoring. One exemplary need for reliable determination of oxygen saturation levels in the human brain arises in the context of the millions of surgical procedures performed under general anesthesia every year. One statistic recited in U.S. Pat. No. 5,902,235 is that at least 2,000 patients die each year in the United States alone due to anesthetic accidents, while numerous other such incidents result in at least some amount of brain damage. Certain surgical procedures, particularly of a neurological, cardiac or vascular nature, may require induced low blood flow or pressure conditions, which inevitably involves the potential of insufficient oxygen delivery to the brain. Many surgical procedures also involve the possibility that a blood clot or other clottable material can break free, or otherwise get introduced into the bloodstream, and travel to the brain to cause a localized or widespread ischemic event therein. At the same time, the brain is highly intolerant to oxygen deprivation, and brain cells will die (become infarcted) within a few minutes if not sufficiently oxygenated. Accordingly, the availability of immediate, accurate and reliable information concerning brain oxygenation levels is of critical importance to anesthesiologists and surgeons, as well as other involved medical practitioners. 
         [0006]    Pulse oximetry, in which infrared sources and detectors are placed across a thin part of the patient&#39;s anatomy such as a fingertip or earlobe, has arisen as a standard of care for all operating room procedures. However, pulse oximetry provides only a general measure of blood oxygenation as represented by the blood passing by the fingertip or earlobe sensor, and does not provide a measure of oxygen levels in vital organs such as the brain. In this sense, the surgeons in the operating room essentially “fly blind” with respect to brain oxygenation levels, which can be a major source of risk for patients (e.g., stroke) as well as a major source of cost and liability issues for hospitals and medical insurers. 
         [0007]    Valid NIR cerebral oxygenation level readings can provide crucial monitoring data for the surgeon and other attending medical personnel, providing more direct data on brain oxygenation levels than pulse oximeters while being just as safe and non-invasive as pulse oximeters. Generally speaking, such systems involve the attachment of an NIR probe patch, or multiple such NIR probe patches, to the forehead and/or other available skin surface of the head. Each NIR probe patch usually comprises one or more NIR optical sources for introducing NIR radiation into the cerebral tissue and one or more NIR optical receivers for detecting NIR radiation that has migrated through at least a portion of the cerebral tissue. One or more oxygenation level metrics are then provided on a viewable display in a digital readout and/or graphical format. 
         [0008]      FIG. 1A  illustrates a conceptual block diagram of a continuous wave spectrophotometer (CWS) system  102  according to the prior art. CWS-based systems are known in the art and are discussed, for example, in WO1992/20273A2 and WO1996/16592A1. CWS system  102  comprises a CWS modulator  104  that modulates optical source(s)  106 , the optical radiation propagating through tissue T to optical radiation detector(s) such as a photodiode  108 . Electrical signals corresponding to the received optical radiation are demodulated by CWS demodulation circuitry  110  and processed by processor  112  to result in an output SO 2  reading  114  which, for conventional CWS-based systems. Generally speaking, as used herein, a CWS-based system is one for which intensity measurements, but no phase measurements, for the detected radiation are processed to compute SO 2  readings. At present, absolute measurement of chromophore concentration in CWS system is still not feasible due to difficulty in measuring optical pathlength of photons traversing the live tissue. Therefore, the pathlength of photons might be longer than the distance traveled between light source and detector. Hence, during a specific activity, only relative changes in chromophore concentration rather than absolute chromophore concentration can be calculated, by measuring the physiological range at a point of interest from a baseline level. Accordingly, the SO 2  reading  114  is denoted in  FIG. 1  as a non-absolute (relative, trend-only) SO 2  metric. 
         [0009]      FIG. 2  illustrates a conceptual block diagram of a phase modulation spectrophotometer (PMS) system  202  for providing oxygen saturation readings. PMS-based systems, which are sometimes termed intensity modulation spectroscopy systems and sometimes termed frequency domain spectroscopy systems, are known in the art and are discussed, for example, in U.S. Pat. No. 4,972,331, U.S. Pat. No. 5,187,672, and WO1994/21173A1. Generally speaking, as used herein, a PMS-based system is one for which both intensity measurements and phase measurements for the detected radiation are processed to compute SO 2  readings. PMS system  202  comprises a PMS modulator  204  that modulates optical source(s)  206 , the optical radiation propagating through tissue T to an optical radiation detection system including collector optics  207  (for example, windows and prism reflectors in a probe patch) that transfer the optical radiation to optical fibers  208  that, in turn, transfer the optical radiation to a photomultiplier tube (PMT)  209 . Electrical signals from the PMT tube  209  corresponding to the received optical radiation are demodulated by PMS demodulation circuitry  210  and processed by processor  212  to result in an output SO 2  reading  214  which, advantageously, can be an absolute oxygen saturation reading. 
         [0010]    For oxygen saturation monitoring (SO 2  monitoring) in the brain it is often more desirable for to be provided with absolute SO 2  readings than relative SO 2  readings, for at least the reason that a given percentage drop in SO 2  level may, or may not, represent a critical ischemic situation. By way of example, it has been found in practice that absolute SO 2  readings in the range of 60%-80% are usually associated with non-problematic conditions, with the SO 2  reading varying within the 60%-80% range for any of a variety of normal, non-problematic reasons, whereas absolute SO 2  readings below 60% can be associated with a problematic ischemic condition. Accordingly, by way of example, a fifteen percent relative drop in SO 2  from an absolute reading of 75% to an absolute reading of 64%, as measured by a PMS-based system, can be considered non-problematic, while a fifteen percent relative drop in SO 2  from 65% to 55%, as measured by a PMS-based system, could be reason for alarm. However, if a CWS-based system is being used, the relative drop of fifteen percent is the only information being provided by the monitoring system, and therefore the medical personnel face an uncertain situation because they do not know if that drop is truly problematic or not, making relative SO 2  readings generally less desirable than absolute SO 2  readings in this environment. 
         [0011]    Unfortunately, PMS-based systems contain certain practical limitations compared to CWS-based systems that make PMS-based system much more expensive and less robust in everyday clinical environments. Whereas CWS modulation rates are relatively low, typically only around 25 kHz or lower (not tending all the way to DC primarily to avoid unacceptable 1/f noise levels), PMS modulation rates are relatively very high in the 100 MHz-1000 MHz range. The lower modulation rate of CWS makes the modulation and demodulation circuitry relatively easy and less expensive to implement in comparison to PMS modulation and demodulation circuitry. Furthermore, electromagnetic interference issues become more important and complex in the PMS modulation range of 100 MHz 1000 MHz, for at least the reason that over-the-air television signals, FM radio signals, etc. fall in that frequency band, making electromagnetic shielding requirements more important and the performance of the device less robust. 
         [0012]    Importantly, PMS-based systems further tend to suffer from a more limited penetration depth than CWS-based systems. Physically, in the relevant radiation wavelengths in the neighborhood of 700-800 nm, attenuation of propagating radiation is substantially higher when that radiation is modulated at 100 MHz-1000 MHz than when that radiation is modulated at only 25 KHz. Also, the detector size for PMS-based systems (see  FIG. 2 , A D,PMS ) needs to remain small in order for discernable signal phase delays to remain intact. Even when highly sensitive (and expensive, bulky, and complex) PMT detector systems are used, the source-to-detector spacing in PMS-based systems is more limited than for CWS-based systems. CWS-based systems are less sensitive to detector size, allowing larger-area detectors (see  FIG. 1 , A D,CWS ), and therefore greater source-to-detector spacing and/or the advantageous ability to use cheaper, less expensive detectors such as photodiodes rather than PMT detector systems. One thumbnail empirical relationship is that penetration depth tends to be about one-half of the source-detector spacing, for both CWS systems (D CWS ≈S CWS /2, see  FIG. 1 ) and PMS systems (D PMS ≈S PMS /2, see  FIG. 2 ). By way of nonlimiting numerical example, the source-detector spacing in many PMS-based systems is often limited to 4-6 cm, making the penetration depth limited to about 2-3 cm. In contrast, the source-detector spacing in many CWS-based systems can substantially greater than the range of 4-6 cm, although, as discussed supra, CWS-based systems such as those of  FIG. 1  can only provide non-absolute, trend-only output readings. 
         [0013]      FIGS. 3A-3E  summarize, in simplified form, the well-accepted “slope method” that is applicable to PMS-based systems and, in a reduced form, to CWS-based systems. Descriptions of the slope method can be found, for example, in Fantini. Franceschini, and Gratton, “Semi-Infinite-Geometry Boundary Problem For Light Migration In Highly Scattering Media: A Frequency-Domain Study In The Diffusion Approximation,” J. Opt. Soc. Am. B, Vol. 11, pp. 2128-38 (1994) and Fantini, Hueber, and Franceschini, et. al., “Non-Invasive Optical Monitoring of the Newborn Piglet Brain Using Continuous-Wave and Frequency-Domain Spectroscopy,” Phys. Med. Biol., Vol. 44, pp. 1543-1563 (1999), each of which is incorporated by reference herein. For PMS-based systems, the basis of the slope method is (i) for any particular NIR radiation wavelength, a plot of log (r 2 I) versus r (where I is the measured intensity and r is the source-detector distance,  FIG. 3B ) has a relatively constant slope K a  over an appreciably useful range of distances, (ii) a plot of φ versus r (where φ is the measured phase,  FIG. 3C ) also has a relatively constant slope K p  over an appreciably useful range of distances, and (iii) the values of K a  and K p  can be used to compute the absorption coefficient μ a  and the effective or reduced scattering coefficient μ s ′ for that NIR radiation wavelength ( FIG. 3D ), where w is the angular frequency corresponding to the source intensity modulation and v is the speed of light in the tissue. For CWS-based systems, the same intensity-based slope K a  is computed ( FIG. 3B ), but there is no phase measurement available for a phase-based slope measurement. For CWS-based systems, the absorption coefficient μ a  is computed from the value of K a  in conjunction with a simple fixed estimate of the effective scattering coefficient μ s ′ ( FIG. 3E ). 
         [0014]    For both PMS-based and CWS-based cases, the absorption coefficient μ a  for multiple NIR wavelengths (on opposite sides of the isosbestic wavelength for oxygenated and deoxygenated hemoglobin) can then be used to compute the oxygenated hemoglobin saturation value SO 2 , such as by using the well-known empirical relationship of  FIG. 3F  for the particular NIR wavelengths of 690 nm and 830 nm. Generally speaking, consistent with the more precise measurement of the absorption coefficient μ a  based on both intensity and phase measurement, the SO 2  reading for the PMS-based case can be characterized as an absolute percentage value. Generally speaking, consistent with the generally rougher computation of the absorption coefficient μ a , the SO 2  reading for the CW-based case measurements should be provided as a non-absolute (relative, trend-only) reading on an output display. 
         [0015]    Thus, generally stated, the CWS-based system of  FIG. 1  is capable of providing SO 2  readings applicable to substantially greater tissue depths than the PMS-based system of  FIG. 2 , but only in a non-absolute SO 2  context, while the PMS-based system of  FIG. 2  is capable of providing absolute SO 2  readings, but only for generally shallower tissue depths than the CWS-based system of  FIG. 1 . It would be desirable to provide a non-invasive spectrophotometric monitoring system that is capable of providing absolute oxygen saturation level measurements applicable to relatively deep levels in the human brain, the measurements being sufficiently practical to obtain and yet being sufficiently reliable for use in surgical environments or other clinical settings in which the patient may slip from a non-ischemic condition to an ischemic condition. However, it is to be appreciated that the scope of the preferred embodiments described hereinbelow is not limited to cerebral oxygen saturation monitoring, but also includes devices and related methods for practical, reliable determination of absolute oxygen saturation levels in relatively deep parts of anatomy other than the human brain, such as the human kidney. Other issues arise as would be apparent to a person skilled in the art in view of the present disclosure. 
         [0016]    According to one preferred embodiment, a method for non-invasive spectrophotometric monitoring of oxygen saturation levels based on a combination of combined continuous wave spectrophotometry (CWS) and phase modulation spectrophotometry (PMS) is provided. The method is applied for a patient monitoring session that includes (i) a reference interval, and (ii) a monitoring interval subsequent to the reference interval. First information acquired from PMS-based monitoring of a patient tissue volume during the reference interval is received, the first information being representative of one or more absolute oxygen saturation levels in one or more respective relatively shallow regions of the tissue volume. Second information acquired from CWS-based monitoring of the tissue volume during the reference interval is also received, the second information being representative of one or more non-absolute oxygen saturation levels in one or more respective relatively deep regions of the tissue volume. Based on the first and second information associated with the reference interval, a mapping is automatically determined between the second information and at least one estimated absolute oxygen saturation metric applicable to one or more respective relatively deep regions. Then, on a continuing basis during the monitoring interval, the second information acquired from the CWS-based monitoring is mapped into estimated absolute oxygen saturation metrics applicable to the one or more respective relatively deep regions by applying the determined mapping, and the estimated absolute oxygen saturation metrics are continuously displayed on a display output. In another preferred embodiment a computer readable medium tangibly embodying computer code is provided, the computer code causing all or a substantial part of the above-described method to be carried out when executed by one or more processors. 
         [0017]    Also provided is a system for non-invasive spectrophotometric monitoring of oxygen saturation levels in a tissue volume of a patient during a patient monitoring session, the patient monitoring session including a reference interval and a monitoring interval subsequent to the reference interval. The system comprises a PMS subsystem for PMS-based monitoring of the tissue volume, the PMS subsystem generating first information representative of one or more absolute oxygen saturation levels in one or more respective relatively shallow regions of the tissue volume. The system further comprises a CWS subsystem for CWS-based monitoring of the tissue volume, the CWS subsystem generating second information representative of one or more non-absolute oxygen saturation levels in one or more respective relatively deep regions of the tissue volume. The system further comprises a processing system, such as a programmable computer, that is programmed to determine, based on the first information and the second information as acquired during the reference interval, a mapping between the second information and one or more estimated absolute oxygen saturation metrics applicable to the one or more relatively deep regions of the tissue volume. The programmable computer is further programmed to compute, on a continuing basis during the monitoring interval, the one or more estimated absolute oxygen saturation metrics applicable to the respective one or more relatively deep regions by applying the determined mapping to the second information as acquired during the monitoring interval. The system further comprises an output display for displaying, on a continuing basis during the monitoring interval, the one or more estimated absolute oxygen saturation metrics applicable to the respective one or more relatively deep regions of the tissue volume. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0018]      FIG. 1  illustrates tissue oxygen saturation monitoring using continuous wave spectrophotometry (CWS) according to the prior art; 
           [0019]      FIG. 2  illustrate tissue oxygen saturation monitoring using phase modulation spectrophotometry (PMS) according to the prior art; 
           [0020]      FIGS. 3A-3F  illustrate a slope method for computing oxygen saturation levels; 
           [0021]      FIG. 4  illustrates a hybrid CWS-PMS oxygen saturation monitoring system that uses combined continuous wave spectrophotometry (CWS) and phase modulation spectrophotometry (PMS) according to a preferred embodiment; 
           [0022]      FIG. 5  illustrates oxygen saturation monitoring using a combination of continuous wave spectrophotometry (CWS) and phase modulation spectrophotometry (PMS) according to a preferred embodiment; 
           [0023]      FIGS. 6A-6C  illustrates a probe unit of a hybrid CWS-PMS cerebral oxygen level measurement system according to a preferred embodiment; 
           [0024]      FIG. 7A  illustrates a conceptual top view of the a probe unit of  FIGS. 6A-6C  as applied to the head of a patient; 
           [0025]      FIG. 7B  illustrates an output display of a hybrid CWS-PMS cerebral oxygen level measurement system hybrid according to a preferred embodiment; 
           [0026]      FIG. 8A  illustrates a conceptual top view of the a probe unit of  FIGS. 6A-6C  as applied to the head of a patient; 
           [0027]      FIG. 8B  illustrates an output display of a hybrid CWS-PMS cerebral oxygen level measurement system hybrid according to a preferred embodiment; 
           [0028]      FIG. 9  illustrates a probe unit of a hybrid CWS-PMS renal oxygen level measurement system according to a preferred embodiment; 
           [0029]      FIG. 10  illustrates a cross-section of an abdominal tissue volume to which is two of the probe units of  FIG. 9 ; 
           [0030]      FIGS. 11A-11B  illustrate a user display of a hybrid CWS-PMS renal oxygen level measurement system according to a preferred embodiment; and 
           [0031]      FIG. 12  illustrates a conceptual plot of source power for different CWS sources of a cerebral oxygen level measurement system according to a preferred embodiment. 
       
    
    
     DETAILED DESCRIPTION 
       [0032]    Hybrid CWS-PMS cerebral oxygen saturation monitoring system using combined continuous wave spectrophotometry (CWS) and phase modulation spectrophotometry (PMS) according to one or more preferred embodiments is based at least in part on a finding that, for many practical clinical applications, it is sufficiently accurate and practical to assume that the SO 2  levels throughout the brain are substantially uniform prior to the beginning of a surgical procedure, the ingestion of a drug, the application of an external stimulus, or more generally some event (termed herein a “subject medical event”) over the course of which SO 2  monitoring will be desired. Thus, during a generally quiescent period subsequent to the mounting of the CWS and PMS hardware on the head of the patient but prior to the onset of the subject medical event, absolute SO 2  readings from the PMS hardware, which are technically limited in applicability to relatively shallow brain regions near the PMS source-detector pairs, can be considered as being applicable to all regions of the brain, including relatively deep-level regions that are technically only being “reached” by the CWS source-detector pairs. Based on this premise, absolute PMS-based SO 2  readings and non-absolute CWS SO 2  readings acquired during that quiescent period (termed herein a “reference interval”) can be processed to generate a mapping (which can be a direct scaling in a simplest preferred embodiment) between the non-absolute CWS SO 2  readings and an estimate of absolute SO 2  levels in the corresponding relatively deep regions of the brain. Once this mapping is determined, it can be applied on an ongoing basis subsequent to the onset of the medical event (during a “monitoring interval”) to compute estimated absolute SO 2  readings applicable to the relatively deep-level regions from the non-absolute CWS SO 2  readings. 
         [0033]      FIG. 4  illustrates a hybrid CWS-PMS oxygen saturation monitoring system  402  that uses combined continuous wave spectrophotometry (CWS) and phase modulation spectrophotometry (PMS) according to a preferred embodiment, comprising a housing  404  and a probe unit  406 . The system  402  includes a CWS-based monitoring subsystem  408  comprising CWS-based hardware  410  and at least one CWS-based source-detector pair (S CWS , C CWS ). The system  402  further includes a PMS-based monitoring subsystem  412  comprising PMS-based hardware  416  and at least one PMS source-detector unit (S PMS , C PMS ). The system  402  further comprises a processor  418 , an output display  422 , the processor being configured and programmed to achieve the functionalities described herein. A user interface is provided that includes a calibration trigger input  420  that is manually instantiated by a user of the system (for example, just prior to the beginning of the subject medical event) to signal an end of a quiescent reference interval and the beginning of a monitoring interval. The calibration trigger input  420  can be provided in a variety of ways, such as with a hardware button, a softbutton pressable by mouse click, a touchscreen button, etc. An arbitrary time value “0” is shown in  FIG. 4  as representing the time of the manual calibration trigger input from the user. Illustrated on the output display  422  is a time plot identifying a reference interval (REF) and a monitoring interval (MON), and displaying a time plot  424  of the desired estimated absolute SO 2  reading applicable to the relatively deep-level region  495  during the monitoring interval MON. 
         [0034]    Conceptually illustrated in  FIG. 4  is a relatively deep region  495  that is “reached” only by the CWS-based monitoring subsystem  408 , and a relatively shallow region  493  to which the “reach” of the PMS-based monitoring subsystem  412 . by the CWS-based monitoring subsystem  408 . The spatial probe arrangements can be provided in a variety of different ways that cause the regions  495  and  493  to be spatially distinct, partially overlapping, or substantially overlapping, each without departing from the scope of the preferred embodiments. For one preferred embodiment, the source-detector spacing for the PMS source-detector pair units is less than about 6 cm, which corresponds to a thumbnail estimate of the relatively shallow region  493  as being less than about 3 cm deep, while the source-detector spacing for the CWS source-detector pair is greater than about 6 cm, which corresponds to a thumbnail estimate of the relatively deep region  495  as being greater than about 6 cm deep. Although this 3 cm depth demarcation (6 cm source-detector spacing demarcation) between “relatively shallow” and “relatively deep” has been found to be a useful demarcation for many of today&#39;s practical PMS and CWS systems, this example is by no means intended to limit the scope of the preferred embodiments. More generally, for purposes of the described preferred embodiments, the demarcation between “relatively shallow” and “relatively deep” depths can be associated with a practical maximum source-detector spacing reliably achieved by the PMS subsystem to be used, and which is exceeded by the CWS subsystem to be used. Thus, for example, if the particular PMS subsystem to be used has a reliably achieved practical maximum source-detector spacing of about 4 cm, then the demarcation between “relatively shallow” and “relatively deep” would be about 2 cm, whereas if the particular PMS subsystem to be used has a reliably achieved practical maximum source-detector spacing of about 8 cm, then the demarcation between “relatively shallow” and “relatively deep” would be about 4 cm. 
         [0035]      FIG. 5  illustrates steps executed by the processor  418  in conjunction with the user interface and user display  422  according to a preferred embodiment. At step  502 , in association with the reference interval, an absolute oxygen saturation metric SO 2,493  applicable to the relatively shallow region  493  (or other information from which that value can be derived) is received from the from the PMS monitoring subsystem  412 . At step  504 , in association with the reference interval, a non-absolute oxygen saturation metric R 495  applicable to the relatively deep region  495  (or other information from which that value can be derived) is received from the from the CWS monitoring subsystem  408 . At step  506  a mapping is determined based on SO 2,493  and R 495 , between the non-absolute oxygen saturation level and an estimated absolute oxygen saturation metric SO 2,495,ABS  (t) applicable to the relatively deep region  495 . As one of many examples within the scope of the present teachings,  FIG. 5  illustrates a relatively simple mapping  550  in which is a scaling of R 495  by a constant scaling factor  552 , wherein the constant scaling factor  552  is that which, when multiplied by R 495 ( 0 ) results in SO 2,493 ( 0 ). The values for R 495 ( 0 ) and SO 2,493 ( 0 ) can be instantaneous values at time 0, or alternatively can be averaged over some or all of the reference interval. At step  508 , on a continuing basis during the monitoring interval, the non-absolute oxygen saturation level R 495 (t) for the relatively deep region  495  is received from the CWS-based monitoring subsystem  408 . At step  510 , on a continuing basis during the monitoring interval, the estimated absolute oxygen saturation metric SO 2,495,ABS (t) applicable to the relatively deep region  495  is computed by applying the determined mapping  550  to the non-absolute oxygen saturation level R 495 (t) for the relatively deep region  495 . 
         [0036]      FIGS. 6A-6C  illustrates a probe unit  602  of a hybrid CWS-PMS cerebral oxygen level measurement system according to a preferred embodiment, which represents an extension of the preferred embodiments of  FIGS. 4-5  for the case of multiple PMS source-detector pair units (and therefore multiple relatively shallow regions of the tissue volume), multiple CWS sources, and multiple CWS detectors (and therefore multiple relatively deep regions of the tissue volume). Probe unit  602  comprises a headband or other means for supporting/mounting (i) a plurality of PMS source-detector units PMS 1  and PMS 2 , each including plural sources PMSS and detectors PMSD, (ii) a plurality of CWS sources SA, SB, SC, SD, and SF, and (iii) a plurality of CWS detectors D 1 , D 2 , D 3 , and D 4  to the skin of the head of the patient around its periphery in a region above the ears and eyebrows, as shown. Preferably, the head is shaved so that good optical coupling can be achieved all around the head, although it is not outside the scope of the preferred embodiments for “hairbrush” style fiber couplings to be used to obviate the need for shaving the head. 
         [0037]    While many components of the probe unit  602  are omitted from the drawings for clarity of presentation (for example, fiber couplings, optical shielding, waveguides, etc.), it is to be appreciated that a person skilled in the art would be able to construct a probe unit and associated system according to the preferred embodiments in view of the present disclosure without undue experimentation. Unless indicated otherwise herein, any particular PMS source-detector unit PMS 1 , PMS 2 , etc., referenced herein shall be presumed to be accompanied by the necessary radiation collection optics, optical fibers, PMT tube(s), PMS demodulator circuitry, PMS signal processing circuitry, and output display devices as necessary to implement an overall PMS cerebral oxygen level measurement unit that provides a corresponding absolute SO 2  reading. 
         [0038]    The plurality of CWS sources and detectors form the following individual source-detector pairs: SA-D 1 , SB-D 1 , SB-D 3 , SD-D 3 , SF-D 4 , SC-D 4 , SC-D 2 , and SA-D 2 . According to a preferred embodiment, in order to increase CWS source-detector distance and thereby increase CWS penetration depth, each of the CWS detectors comprises a photomultiplier tube (PMT)-based radiation detection scheme. However, provided that sufficient source-detector spacing is facilitated, it would not be outside the scope of the present teachings for photodiode-based detection schemes to be used. Unless indicated otherwise herein, any particular CWS source-detector pair referenced herein shall be presumed to be accompanied by the necessary radiation collection optics, optical fibers, PMT tube(s), CWS demodulator circuitry, and CWS signal processing circuitry as necessary to generate a corresponding relative SO2 reading. According to a preferred embodiment, this relative SO 2  reading is further processed, as described hereinbelow, such that a clinically meaningful absolute SO 2  reading is provided that corresponds to that CWS source-detector pair. 
         [0039]    In operation, only one PMS source or CWS source is firing at any particular moment in time, and is firing at only one of its two or more source wavelengths (e.g., 690 nm or 830 nm). Because the NIR optical signal loss in living tissue such as the brain is extraordinarily high (about a factor of 10 for every cm of source-detector distance), CWS measurement pairs are only established for directly adjacent sources and detectors. However, it would not be outside the scope of the present teachings to also use non-adjacent CWS source-detector pairs (for example, the pair SA-D 3 ) in the event that a meaningful reading could be acquired at D 3  of a signal originating at the source SA. 
         [0040]    In the preferred embodiment of  FIGS. 6A-6C  the CWS sources SD, SB, SA, SC, and SF can be characterized as being at “clockface coordinates” of about 12:30, 3:00, 6:00, 9:00 and 11:30, respectively, where the nose is considered to be at 12:00, while the CWS detectors D 3 , D 1 , D 2 , and D 4  can be considered to be at about 1:30, 4:30, 7:30, and 10:30, respectively. According to another preferred embodiment (not shown), a plurality of CWS sources are distributed at 1:30, 4:30, 7:30, and 10:30 and a plurality of CWS detectors are distributed at 12:00, 3:00, 6:00, and 9:00. 
         [0041]      FIG. 7A  illustrates a simplified version of  FIG. 6C  (omitting the headband and source/detector iconic shapes), and  FIG. 7B  illustrates an output display  702  according to a preferred embodiment, with annotations added for illustrating particular applications of the method of  FIGS. 4-5  supra for the multiple deep-region, multiple shallow-region case. It has been found useful, practical, and sufficiently accurate to assume the head to have a substantially uniform SO 2  prior to the beginning of a surgical procedure, the ingestion of a drug, the application of an external stimulus, or more generally some event (termed herein a “subject medical event”) over the course of which SO 2  monitoring will be desired, and to calibrate one or more CWS source-detector pairs at some point in time t CAL  prior to the onset of the subject medical event based on absolute PMS-based SO 2  readings acquired by one or more PMS source-detector units at the time t CAL  that are located with or near the one or more CWS source-detector pairs. The calibration process comprises (i) computing an absolute PMS-based SO 2  reading L CAL  representative of the assumed-uniform tissue at the time t CAL , such as by taking an average of the absolute PMS-based SO 2  readings of the one or more PMS source-detector units, (ii) for each CWS source-detector pair, determining a numerical calibration factor (scaling factor) that, when multiplied by the relative SO 2  reading at time t CAL , would result in an absolute output reading of L CAL  for that CWS source-detector pair, and (iii) from time t CAL  onward, setting the absolute SO 2  reading for that CWS source-detector pair equal to the product of that numerical calibration factor and the relative SO 2  reading corresponding to that CWS source-detector pair. The time t CAL  should be a sufficient interval (probably about 1 minute or so depending on the system hardware and patient coupling equipment) after an initial connection or reset time t 0  to allow the absolute and relative readings to reach a reasonably quiescent state. 
         [0042]      FIGS. 8A-8B  illustrate an exemplary numerical example corresponding to the preferred embodiment of  FIGS. 7A-7B , respectively, for an exemplary scenario in which an ischemic event begins to affect a part of the brain at a time t s  during the subject medical event. At the time of calibration t CAL , a reference PMS-based absolute SO 2  reading is computed by averaging the PMS-based absolute SO 2  readings for the two relatively shallow regions (e.g., 75% is the average of 76% and 74%), and then a distinct scaling factor is computed for each relatively deep tissue region such that, when multiplied by the non-absolute CWS-based SO 2  metric for that deep region at time t CAL , results in the value of that reference PMS-based absolute SO 2  reading (e.g., that results in a value of 75%). Thereafter, those scaling factors are applied to the corresponding non-absolute CWS-based SO 2  metric for each deep region to result in the estimated absolute SO 2  reading applicable to each deep region. Advantageously, the medical professional can readily see a downward trend pattern in the graphical plots (or, in an alternative preferred embodiment, numerical output readings) that can be readily used to localize the area of the ischemic event. As a further advantage, the severity of ischemic event can be assessed by looking at the absolute SO 2  readings for the relevant CWS source-detector pairs, and seeing if they are falling below a dangerous absolute lower limit (such as 60% for the numerical clinical example given previously). 
         [0043]      FIG. 9  illustrates a probe unit  902  of a hybrid CWS-PMS renal oxygen level measurement system according to a preferred embodiment, which is analogous to the probe unit  602  of  FIGS. 6A-6C , supra, except that it comprises a single CWS source-detector pair and a single PMS measurement unit. As with the CWS source-detector pairs of  FIGS. 6A-6C , it is preferable for a photomultiplier tube (PMT)-based detection system (not shown) to be used for optical detection, so that the distance “d” is between about 15-16 cm. For another preferred embodiment the distance “d” can be between 10-20 cm. A PMS source-detector unit “PMS” is provided approximately halfway between the source S and detector D. 
         [0044]      FIG. 10  illustrates a cross-section of an abdomen to which is applied an instance of the probe unit  902  for each of the left kidney (unit  902 L) and right kidney (unit  902 R). While calibration of a hybrid CWS-PMS renal oxygen level measurement system is presented herein assuming dual simultaneous probe units  902 L and  902 R, the methods can be readily adapted for a single probe unit  902  that is shifted manually between the left and right kidneys. As illustrated conceptually in  FIG. 10 , the PMS units PMSL and PMSR provide absolute SO 2  for relatively limited depths into subdermal fat tissue, while the CWS source-detector pairs SL-DL and SR-DR achieve substantially greater penetration depth that can encompass a significant portion of the kidney. 
         [0045]      FIGS. 11A-11B  illustrate a user display  1102  of a hybrid CWS-PMS renal oxygen level measurement system according to a preferred embodiment at different times, with annotations added for illustrating a method for calibrating CWS source-detector pairs of a hybrid CWS-PMS renal oxygen level measurement system according to a preferred embodiment. Unlike with the brain oxygen saturation monitoring scenarios described above, it is substantially less likely that the monitoring system will have been put in place before the onset of an ischemic kidney event (or suspected ischemic kidney event). Rather, it will be more likely that the monitoring system will be used to detect whether an ischemic kidney event is already taking place, such as when the patient arrives at the medical facility with kidney pain, although the preferred embodiments can certainly be used for ongoing prospective monitoring of an asymptomatic patient as well. 
         [0046]    It has been found useful, practical, and sufficiently accurate to assume that an (i) ischemic kidney event, if it has occurred, has only affected one kidney and not the other, and that (ii) the general area of the unaffected kidney including the tissue between that kidney and the probe unit  902  can be approximated as having a generally uniform SO 2  level. Shown in  FIG. 11A  are plots of the relative SO 2  readings for the left and right kidneys at some time subsequent to the placement of the monitoring system on the patient ( FIG. 10 ) or system reset such that a quiescent state is reached (e.g., about 1 minute afterward), but prior to a calibration procedure according to a preferred embodiment, which can be instituted at an otherwise arbitrary time t 0 . Absolute SO 2  readings are also being taken by the PMS units PMSL and PMSR and output on the user display but are omitted from  FIGS. 11A-11B  for clarity of presentation. 
         [0047]    As of the time t 0 , the absolute SO 2  readings from the PMS units PMSL and PMSR are presumed to have reached reasonably quiescent values denoted here as PMSL( 0 ) and PMSR( 0 ), respectively, or can be time-averaged to produce those values. As of the time t 0 , the relative SO 2  readings from SL-DL and SR-DR are presumed to have reached reasonably quiescent values denoted as L( 0 ) and R( 0 ), respectively, or can be time averaged to produce those values. According to a preferred embodiment, a calibration rule (i.e., a mapping) is applied to generate an absolute SO 2  level X to which the SL-DL relative output is mapped by virtue of the scaling axis  1106 , as well as to generate an absolute SO 2  level Y to which the SR-DR relative output is mapped by virtue of the scaling axis  1108 , and these computed scalings remain fixed thereafter. According to one preferred embodiment, the calibration rule, as illustrated in box  1104 , is that if L( 0 ) is greater than or equal to R( 0 ) (that is, the right-side kidney is detected as having the ischemic condition), then X is assigned to the average of PMSL( 0 ) and PMSR( 0 ) Y is assigned to the value of X times R( 0 )/L( 0 ), whereas if L( 0 ) is less than R( 0 ) (that is, the left-side kidney is detected as having the ischemic condition), then Y is assigned to the average of PMSL( 0 ) and PMSR( 0 ) and X is assigned to the value of Y times L( 0 )/R( 0 ). 
         [0048]    According to another preferred embodiment, the calibration rule is that if L( 0 ) is greater than or equal to R( 0 ), then X is assigned to PMSL( 0 ) and Y is assigned to the value of X times R( 0 )/L( 0 ), whereas if L( 0 ) is less than R( 0 ), then Y is assigned to PMSR( 0 ) and X is assigned to the value of Y times L( 0 )/R( 0 ). In other words, the calibration to an absolute value is based on an SO 2  uniformity assumption with the nearby PMS reading for whichever kidney (left or right) is yielding the higher CWS relative SO 2  value, and then the opposing side is scaled to an absolute value based on a ratio of the lower CWS relative SO 2  value to the higher CWS relative SO 2  value. 
         [0049]      FIG. 12  illustrates a conceptual plot of source power for a probe unit  1202  of a cerebral oxygen level measurement system according to a preferred embodiment, which can optionally be a hybrid CWS-PMS probe unit, although the scope of the present teachings is not so limited. Detectors are omitted from  FIG. 12  for clarity of presentation, with only sources being shown. According to a preferred embodiment, the average operating laser power for sources near the back of the head, which are very distant from the retina, is turned up very high and is limited only by FDA regulations on laser power to the head in general. In contrast, as the position of the source draws nearer to the front of the head, the source power is reduced in order to avoid retinal damage or unpleasant visual sensations due to laser light incident upon the retina. By maximizing power in this way, safety and patient comfort are accommodated, while also maximizing penetration depth for brain tissue closer to the back of the head, since source-detector separation can be increased with increased amounts of source power. By way of example and not by way of limitation, the average laser power for sources S 1  and S 9  may be limited to about 30 mW due to their proximity to the retina, whereas the average laser power for sources S 3 -S 7  might be about 500 mW depending on applicable FDA regulatory limits, and keeping in mind that only one of them is firing at any given time. 
         [0050]    Whereas many alterations and modifications of the present invention will no doubt become apparent to a person of ordinary skill in the art after having read the foregoing description, it is to be understood that the particular embodiments shown and described by way of illustration are in no way intended to be considered limiting. By way of example, whereas one or more of the above-described preferred embodiments includes a hybrid CWS-PMS scheme in which absolute PMS SO 2  readings are used to provide a basis for calibrating relative CWS SO 2  readings to an absolute scale, in an alternative preferred embodiment there is provided a hybrid TRS (time resolved spectrophotometry)-PMS scheme in which absolute TRS SO 2  readings are used to provide a basis for calibrating non-absolute CWS SO 2  readings to an absolute scale. Therefore, reference to the details of the embodiments are not intended to limit their scope, which is limited only by the scope of the claims set forth below.