Patent Publication Number: US-2009234245-A1

Title: Non-invasive monitoring of intracranial pressure

Description:
FIELD 
     This patent specification relates to the monitoring of a physiological condition of a patient using non-invasive measurement techniques. More particularly, this patent specification relates to the monitoring of intracranial pressure (ICP) using non-invasive optical techniques. 
     BACKGROUND AND SUMMARY OF THE DISCLOSURE 
     Intracranial pressure refers to the pressure exerted by the cranium on the tissue and fluid matter contained inside the cranium, which includes brain tissue, cerebrospinal fluid, and blood circulating in the brain. Typical values of ICP for a patient at rest are in the range of 10-15 mm Hg (0.013-0.020 atm). Elevated ICP levels are generally undesirable and are often a result of a traumatic head injury, an infectious disease such as meningitis, or another pathological condition such as brain tumor. For an adult, an elevated ICP above 40 mm Hg is likely to cause severe harm, and even pressures between 25 and 30 mm Hg are usually fatal if prolonged. Detection of ICP variations is recognized as an important tool in monitoring the state of injured patients, diagnosing symptoms of potentially diseased patients, and monitoring patient health during surgery or other therapeutic interventions. 
     Although various proposals have been made for non-invasive ICP monitoring, it is still generally recognized that reliable detection of ICP variations requires invasive measurement devices. However, such invasive techniques involve exposing and potentially traumatizing the brain tissue, which can increase the risk of infection, hemorrhage, leakage of cerebrospinal fluid, and other problems that can actually worsen the patient&#39;s condition. 
     Described in this patent specification are methods, systems, and related computer program products for non-invasive detection of ICP variations using optical techniques in the visible and/or near infrared regime. According to one preferred embodiment, optical radiation is propagated transcranially into the intracranial compartment, and optical radiation is detected that has migrated through at least a portion of the intracranial compartment and back out of the cranium. At least one signal representative of the detected optical radiation is processed to extract therefrom at least one component signal that varies in time according to at least one of an intrinsic physiological oscillation in the patient and an externally driven oscillation in the patient. For one preferred embodiment, the intrinsic physiological oscillation comprises at least one of an intrinsic respiratory oscillation and a cardiac oscillation. For one preferred embodiment, the externally driven oscillation comprises at least one of an external skull vibrator oscillation and a ventilated respiratory oscillation. The at least one extracted component signal is then processed to generate an output signal representative of the ICP variations in the intracranial compartment. 
     According to another preferred embodiment, a method for ICP monitoring is provided in which an absolute ICP of a patient is monitored using an invasive ICP monitoring device, such as a subarachnoid bolt. Simultaneously with the invasive ICP monitoring, a non-invasive ICP monitoring device is placed in optical communication with the head of the patient, the non-invasive ICP monitoring device using optical radiation to transcranially detect variations in the magnitudes of periodic intracranial matter oscillations intrinsically and/or extrinsically induced, the magnitude variations being indicative of intracranial matter compliance variations brought about by ICP changes. The absolute ICP from the invasive ICP monitoring device is used to calibrate the non-invasive ICP monitoring device. When the invasive ICP monitoring device is removed, ICP monitoring is continued by maintaining the non-invasive ICP monitoring device in optical communication with the head of the patient. 
     According to another preferred embodiment, a method for non-invasive ICP monitoring is provided, comprising applying a plurality of discrete mechanical impulses to the head of the patient at a respective plurality of discrete points in time. During each of a plurality of time intervals immediately subsequent to each respective discrete point in time, optical radiation is applied to the patient that propagates transcranially into the intracranial compartment, and optical radiation that has migrated transcranially outward from the intracranial compartment is detected. A plurality of time signals representative of the optical radiation detected during the respective time intervals is then processed to generate an output signal representative of the ICP variations. For one preferred embodiment, the processing comprises, for each of the time signals, computing at least one transient characteristic thereof induced by the mechanical impulse associated therewith. On an impulse over impulse basis, a decreasing value is assigned for the ICP output signal when the computed transient characteristic(s) change toward values indicative of greater intracranial matter compliance, while an increasing value is assigned for the ICP output signal when the computed transient characteristic(s) change toward values indicative of lesser intracranial matter compliance. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates a system for non-invasive monitoring of intracranial pressure (ICP) variations according to a preferred embodiment; 
         FIG. 2  illustrates conceptual side cutaway views of an intracranial compartment at a valley and a peak, respectively, of the respiratory cycle during an interval in which the ICP is relatively low, along with a corresponding plot of a filtered component of the optically detected signal; 
         FIG. 3  illustrates conceptual side cutaway views of the intracranial compartment of  FIG. 2  at a valley and a peak, respectively, of the respiratory cycle during an interval in which the ICP is relatively high, along with the corresponding plot of the filtered component of the optically detected signal; 
         FIG. 4  illustrates a system for non-invasive monitoring of intracranial pressure (ICP) variations according to a preferred embodiment; 
         FIG. 5  illustrates non-invasive monitoring of intracranial pressure (ICP) variations according to a preferred embodiment; 
         FIG. 6  illustrates a method for ICP monitoring according to a preferred embodiment; and 
         FIG. 7  illustrates conceptual time plots corresponding to a method for ICP monitoring according to a preferred embodiment. 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1  illustrates a system  102  for non-invasive monitoring of intracranial pressure (ICP) variations of a patient  101  according to a preferred embodiment. Spectrophotometric systems based on visible and/or near infrared (NIR) radiation for achieving various non-invasive physiological measurements, such as transcranial measurements of oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (Hb) concentrations, have been in various stages of proposal and development for an appreciable number of years. As will be appreciated by one skilled in the art in view of the present disclosure, certain component devices suitable for use within the system  102  are described in several prior disclosures directed to such non-invasive optical HbO/Hb measurement, and their specifics will not be re-described here. Moreover, several of those overall spectrophotometric systems and methods may be advantageously used in conjunction with, or as important components within, a system  102  according to one or more of the preferred embodiments. Examples of such spectrophotometric systems include, but are not limited to: continuous wave spectrophotometers (CWS) as discussed in WO1992/20273A2 and WO1996/16592A1; phase modulation spectroscopic (PMS) units as discussed in U.S. Pat. No. 4,972,331, U.S. Pat. No. 5,187,672, and WO1994/21173A1; time resolved spectroscopic (TRS) units as discussed in U.S. Pat. No. 5,119,815, U.S. Pat. No. 5,386,827, and WO1994/22361A1; and phased array systems as discussed in WO1993/25145A1. All of the patents and patent publications identified above in this paragraph are incorporated by reference herein. Another example of a spectrophotometric system that is particularly suitable for use in conjunction with one or more of the preferred embodiments is discussed in US 2006/0015021A1, which is also incorporated by reference herein. 
     System  102  comprises an optical source  104  that emits radiation having a wavelength in the range of about 500 nm-1000 nm, i.e., in the upper visible and near infrared wavelengths. Light from the optical source  104  is carried by an optical fiber  106  to a source port  114  of an optical coupling device  112  on the forehead of the patient. Light that has migrated through at least a portion of the intracranial compartment and outward again through the cranium is collected at a detection port  116  of the optical coupling device  112  and guided to an optical detector  108  by an optical fiber  110 . For one preferred embodiment, the optical coupling device  112  can be similar to one or more of the optical coupling devices disclosed in U.S. Pat. No. 5,596,987, which is incorporated by reference herein. Preferably, the optical coupling device  112  is designed to be a disposable, one-time-use patch that secures to the forehead using known adhesives. The optical coupling device  112  including the source port  114  and detection port  116  can alternatively be attached to an accessible skin surface elsewhere on the scalp other than the forehead. 
     The detector  108  generates a signal that is representative of the light collected at the detection port  116 . For a relatively simple continuous wave embodiment in which the source  104  emits a monochromatic unmodulated carrier wave, the detector  108  provides a voltage signal V OUT  representing an instantaneous intensity of the light collected at detection port  116 . For one embodiment, the optical source  104  comprises a 4 mW laser diode emitting at 760 nm, and the optical detector  108  comprises a Hamamatsu R928 photomultiplier tube. Although the optical source  104 , optical detector  108 , and optical coupling device  112  are illustrated as distinct components in the example of  FIG. 1 , the scope of the present teachings is not so limited. For example, in other preferred embodiments, the optical source(s) and optical detector(s) can be integrated into a single patch that adheres to the skin surface, such that there is no need for external optical connections to the adhesive patch assembly. Any of a variety of other schemes for causing optical radiation to be introduced into the cranium and for causing optical radiation propagating back out of the cranium to be detected can be used without departing from the scope of the preferred embodiments. 
     As used herein, intracranial compartment refers to the space inside the cranium, while intracranial matter refers broadly to the matter that occupies the intracranial compartment. The intracranial compartment encompasses, and the intracranial matter includes, the dura mater, subdural cavity, arachnoid layer, subarachnoid cavity, pia mater, and brain tissue, along with cerebrospinal fluid contained in the subdural cavity, the blood running throughout to all of the living tissue cells, and the arteries, capillaries, veins, etc., that carry the blood. 
     As used herein, intrinsic physiological oscillation refers to a physiological characteristic or behavior that is brought about autonomically by the patient&#39;s body, that exhibits some form of periodicity, and that directly or indirectly brings about some form of corresponding motion, even if slight, in the intracranial matter of the patient. The corresponding motion can be in the form of positional shifts ranging from very small, localized positional shifts to regional or widespread positional shifts, as well as positional shifts ranging from ordered or patterned positional shifts to disordered or random positional shifts. By way of non-limiting example, as the term positional shift is used herein, intracranial matter that is exhibiting a volume change (e.g., expansion or contraction), whether it be on a local basis or a widespread basis, is also exhibiting a positional shift, since at least some individual portion of that intracranial matter is necessarily moving relative to at least some other individual portion of that intracranial matter as part of that volume change. Likewise, by way of further non-limiting example, as the term positional shift is used herein, a wall of an intracranial artery that is undergoing expansion and contraction as part of a cardiovascular oscillation cycle is also exhibiting positional shifts, since at least some individual portion of that wall is necessarily moving relative to at least some other individual portion of that wall as part of those expansions and contractions. 
     One example of an intrinsic physiological oscillation is the patient&#39;s intrinsic respiratory oscillations, i.e., their natural breathing, which generally occurs at a periodic rate somewhere between 3 breaths per minute (0.05 Hz) and  30  breaths per minute (0.5 Hz). It has been observed that there is some degree of motion, in the form of slight positional shifts/volume changes, in at least a portion of the intracranial matter that occurs in conjunction with the respiratory oscillations of the patient. Another example of an intrinsic physiological oscillation is the patient&#39;s cardiac oscillations, which generally occur at a rate somewhere between 30 beats per minute (0.5 Hz) to 180 beats per minute (3 Hz). It has been observed that there is some degree of motion, in the form of slight positional shifts, that occur with the cardiac oscillations (heartbeat) of the patient. 
     As used herein, externally driven oscillation refers to a physiological characteristic or behavior that is brought about by an external force or input, that exhibits some form of periodicity, and that directly or indirectly brings about some form of corresponding motion, even if slight, in the intracranial matter of the patient. One example of an externally driven oscillation is a ventilated respiratory oscillation that occurs when the patient is placed on a ventilator. Just as with natural breathing, each ventilator-induced breath brings about some degree of positional shift/volume change in at least a portion of the intracranial matter relative to the cranium. However, unlike natural breathing, the operation of a ventilator is at a fixed periodic rate set by an attending clinician. Another example of an externally driven oscillation is an external skull vibrator oscillation brought about by a mechanical vibrator positioned in mechanical communication will the patient&#39;s skull. With advantages to be described further hereinbelow, there is provided in one preferred embodiment a non-invasive ICP monitoring system that includes at least one mechanical vibrator operating at a subsonic frequency in the range of about 3 Hz-30 Hz that is positioned so as to vibrate the patient&#39;s skull at that rate. Preferably, the intensity of the mechanical vibration is high enough to cause some degree of corresponding motion in at least a portion of the intracranial matter, but gentle enough not to cause too much discomfort to the patient. Toward this end, the duty cycle of the mechanical vibrator can be restricted to being “on” for only a few seconds, perhaps 4-5 seconds, every two or three minutes, and “off” otherwise. 
     As may be evident from the incorporated references, the particular physics and mathematics of the scattering and attenuation of the light as it propagates in a banana-shaped migration path from the source port  114  to the detection port  116  can be quite complicated, even when various simplifying assumptions are made regarding the various bone, tissue, and fluid types traversed. However, in accordance with a preferred embodiment, ICP variations are detected in a relatively elegant manner that transcends the particular scheme (CWS, PMS, TRS, etc.) by which the interrogating light waves are modulated, introduced, detected, and evaluated. As described above, it has been observed that at least a portion of the intracranial matter will experience some type of periodic motion relative to the cranium, in the form of positional shift and/or volume change, in correspondence with the above-described intrinsic physiological oscillations. Alternatively or in conjunction therewith, at least some periodic motion of the intracranial matter can be induced in correspondence with externally driven oscillations. Furthermore, it has been found that the amount of this periodic motion will become more restricted at higher ICP pressures and less restricted at lower ICP pressures. If a signal is extracted from the detected radiation that varies in magnitude (or other measurable amount) with an intrinsic physiological oscillation or an externally driven oscillation, then that extracted signal can be used to detect ICP variations regardless of the designed physiological significance (if any) of that extracted signal. Generally speaking, larger variations in that extracted signal will be indicative of a lower ICP, because the intracranial matter is less restricted in its periodic motion when the ICP is lower. Likewise, smaller variations in the extracted signal will be indicative of a higher ICP, because the intracranial matter is more restricted in its periodic motion when the ICP is higher. 
     For one preferred embodiment, a single signal is extracted from the detected radiation that varies in magnitude (or other measurable amount) with a single intrinsic physiological oscillation or a single externally driven oscillation. For another preferred embodiment, multiple signals are extracted from the detected radiation that vary in magnitude (or other measurable amount) with multiple respective intrinsic physiological oscillations, multiple respective externally driven oscillations, or a combination of at least one respective intrinsic physiological oscillation and at least one respective externally driven oscillation. 
       FIG. 1  illustrates an example of the preferred embodiment in which only a single signal is extracted from the detected radiation, wherein that signal varies in magnitude with the intrinsic respiratory oscillations of the patient. Provided in accordance with this preferred embodiment is a first processor  118  (which can alternatively be analog filter circuit) that processes the signal V OUT  in digital form to extract therefrom a component signal C resp  that varies in time according to a timewise respiratory pattern of the patient. Illustrated in  FIG. 1  is a conceptual plot  128  of the component signal C resp , which varies cyclically within an envelope  130   a / 130   b.  Any of a variety of known filtering methods can be used, ranging from a simple numerical digital filter having a passband at typical breathing rates (e.g. between 0.05 Hz and 0.5 Hz), to more complex lock-in schemes using a reference signal from a respiration transducer (not shown), such as a Pneumotrace™ respiration transducer model TSD101 from BIOPAC Systems, Inc., of Goleta, Calif. Optionally, the optical source  104  can be tuned for different wavelengths such that an optimal radiation wavelength (i.e., the radiation wavelength for which the most pronounced and ICP-sensitive component signal C resp  is obtained) can be identified by the user. Alternatively, laboratory tests can be run to determine a best predetermined wavelength. 
     Also provided in accordance with this preferred embodiment is a second processor  119  (which can alternatively be analog filter circuit, and which can optionally be integral with the first processor  118 ) that processes the component signal C resp  in digital form to provide an output signal P rel  indicative of the ICP variations in the intracranial compartment. As part of the processing by the second processor  119 , an envelope magnitude (i.e., the vertical distance between the plot lines  130   a  and  130   b ) of the component signal C resp  is determined. The output signal P rel  is assigned a greater value when the envelope magnitude has a lesser value, and the output signal P rel  is assigned a lesser value when the envelope magnitude has a greater value. System  102  further comprises a user display  120  providing a graphical representation  122  and/or a numerical representation  124  of the ICP output value P rel  as a percentage of a baseline value  126 . 
     It is to be appreciated that envelope magnitude (i.e., the vertical distance between upper and lower envelope lines) represents one of a variety of different amplitude characteristics of the component signal C resp  that can be measured and used in the determination of the output signal P rel  without departing from the scope of the present teachings. More generally, any amplitude characteristic of the component signal C resp  (i.e., any metric that characterizes an AC strength of the component signal C resp ) may be used in place of the envelope magnitude, such as an RMS value, a time average of a rectified version, a standard deviation, a square (or cube, etc) of the peak-to-peak value, and so on, without departing from the scope of the preferred embodiments. Thus, descriptions provided herein with respect to envelope magnitude of the component signal C resp , which are provided for purposes of clarity of presentation, are applicable for other amplitude characteristics of the component signal C resp  as well. 
     The particular nature of the inverse relationship between the envelope magnitude of the component signal C resp  and the output value P rel  (e.g., whether it is a reciprocal relationship, a negative arithmetic relationship, or other inverse relationship) could be determined empirically based on test scenarios by a person skilled in the art without undue experimentation in view of the present disclosure. By way of example, a set of test data can be developed in clinical data-gathering trials by applying the system  102  to a population of patients during periods in which their absolute ICP levels are being monitored by an invasive ICP monitoring device, such as a subarachnoid bolt, which is currently recognized as the “gold standard” in ICP measurement. The outcome of the clinical data-gathering trials can be used to establish a relationship between (i) the percentage of envelope magnitude change from an initial envelope magnitude baseline, and (ii) the percentage of ICP variation from the corresponding initial absolute ICP reading. This can then be used to provide the ICP output value P rel  as a percentage of the baseline value  126 . Depending on the results of the clinical data-gathering trials, it may be possible to establish a set of normative data based on different patient characteristics (e.g., height, weight, body surface area to weight ratio, etc.) to provide a more precise mapping between percent envelope magnitude change and percent ICP change. Indeed, it may even be possible, and would certainly be within the scope of the preferred embodiments, to establish a set of normative data that allows absolute ICP levels to be computed based on certain patient information as combined with the envelope magnitude changes and/or envelope magnitude levels, in which case the P rel  output shown in  FIG. 1  would be replaced by a P abs  output expressed in mm Hg. 
       FIG. 2  illustrates conceptual side cutaway views of an intracranial compartment  204  at a valley (left side) and a peak (right side) of respiratory oscillations during an interval T 1  in which the ICP is relatively low. It is to be appreciated that although the example of respiratory oscillations is presented for clarity of disclosure in correspondence with the example of  FIG. 1 , supra, similar conceptual illustrations apply for other types of intrinsic physiological oscillations and externally driven oscillations. Notably, the terms “valley” and “peak” as used herein do not necessarily represent any particular phase of the respiratory cycle, such as inhale or exhale, but instead simply represent extremes of the intracranial matter motion that occurs during the respiratory cycle, whenever those extremes might occur. Also shown is a corresponding plot  128  of the component signal C resp  across three respiratory cycles. Also illustrated is the cranial bone  202  (the skin above the cranial bone is omitted), the source port  114 , and the detection port  116 . The optical radiation migrates through a generally banana-shaped path  206  between the source port  114  and the detection port  116 . The intracranial compartment  204  includes intracranial matter that is represented conceptually by arbitrarily encircled sections, with four arbitrary ones of the encircled sections being colored black for easier recognition including the sections  211  and  213 . 
     During the peak (right side) of a respiratory cycle, the intracranial matter is deformed toward the cranial bone  202  by a slightly greater amount than during the valley (the drawings are exaggerated for clarity). Thus, for example, there is a greater distance y 1  between sections  211  and  213  during the valley (left side) and a lesser distance y 2  during the peak (right side). It is these slight shifts of the intracranial matter that cause the variations of the detected optical signal as extracted at the respiration frequency range. Notably, although it is believed that much of the intracranial matter shifting is due to subdural cavity deformation between the dura mater and arachnoid layers, the true physiological nature of the deformation (e.g., which tissues are deforming by what amount, is the deformation conformal versus irregular, etc.) is generally irrelevant for the purposes of measuring the ICP variations in accordance with the preferred embodiments. Rather, the main requirement is simply that “something” is deforming, in “some” manner that affects the detected optical signal in “some” measurable way according to the respiration cycle of the patient. 
       FIG. 3  illustrates the intracranial compartment  204  at a valley (left side) and a peak (right side) of the respiratory cycle during an interval T 2  in which the ICP is relatively high. As indicated by a lesser difference (y 3 −y 4 ) than in  FIG. 2  between the valley and peak positions of the sections  211  and  213 , there is less deformation between the valleys and peaks due to the greater ICP level. 
     As used herein, compliance refers to the property of intracranial matter that is illustrated in the examples of  FIG. 2  and  FIG. 3 , that is, the degree of corresponding periodic motion, in the form of positional shifts and/or volume changes, in all or a portion of the intracranial matter as a result of an intrinsic physiological oscillation (such as a respiratory oscillation as used in the above examples) or an externally driven oscillation. When the ICP is lower, the compliance of the intracranial matter increases. When the ICP is higher, the compliance of the intracranial matter decreases. Thus provided in accordance with one aspect of the present teachings is a non-invasive ICP measuring device that uses optical radiation to transcranially detect variations in the magnitudes of periodic intracranial matter oscillations that are intrinsically and/or extrinsically induced, the magnitude variations being indicative of intracranial matter compliance variations brought about by ICP changes. 
       FIGS. 4A  illustrates a system  401  for non-invasive monitoring of intracranial pressure (ICP) variations of a patient  101  according to a preferred embodiment in which multiple signals are extracted from the detected radiation that vary in magnitude (or other measurable amount) with multiple respective intrinsic physiological oscillations, multiple respective externally driven oscillations, or a combination of at least one respective intrinsic physiological oscillation and at least one respective externally driven oscillation. For one preferred embodiment, each of the multiple signals is separately filterable (or otherwise extractable) from the detected radiation by virtue of a distinct set of frequencies occupied by its underlying intrinsic physiological oscillation or externally driven oscillation. Upon extraction, each of the extracted signals is individually processed to determine an intracranial matter compliance metric, such as the envelope magnitude, corresponding to the underlying intrinsic physiological oscillation or externally driven oscillation. 
     Generally speaking, all of the intracranial matter compliance metrics (e.g., envelope magnitudes) will share a common characteristic in that each will generally increase as the ICP decreases, and that each will generally decrease as the ICP increases. However, it has been found that a rich variety of clinically interesting and relevant information can arise from the fact that these different intracranial matter compliance metrics (e.g., envelope magnitudes) will generally exhibit different differential characteristics with changing ICP as a function of the prevailing absolute level of ICP. By way of example, letting the variable E R  represent the respiratory intracranial matter compliance metric (e.g., envelope magnitude of the extracted respiratory component of the detected optical signal), and letting the variable E C  represent the cardiac intracranial matter compliance metric (e.g., envelope magnitude of the extracted cardiac component of the detected optical signal), it has been found that E R  tends to diminish rapidly with increasing ICP when the absolute ICP is at moderate levels. However, as the absolute ICP increases further, E R  tends asymptotically toward zero, such that at high levels of absolute ICP, E R  metric ceases to change in any measurable way with increased ICP. In contrast, the cardiac envelope E C  tends to be quite robust against increases in absolute ICP, and maintains appreciable nonzero values even for high levels of absolute ICP. In accordance with a preferred embodiment, both of the metrics E R  and E C  are computed from the detected signal information, and their values relative to each other are analyzed (such as by taking their ratio, difference, etc.) to yield increased precision in the ICP determination process and/or to derive other useful information regarding the health of the patient. The specific ways in which E R  and E C  can be advantageously processed can be determined, for example, by using data from a large clinical data-gathering trial, where E R  and E C  are tracked along with absolute ICP and other vital signs, and patterns and/or statistical correlations in the data can be developed. Indeed, it would not be outside the scope of the preferred embodiments for a set of normative data to be developed using multivariate correlations among E R , E C , E V  (e.g., envelope magnitude of the extracted subsonic vibratory component of the detected optical signal), and other intracranial matter compliance metrics such that the non-invasive ICP monitoring device can be automatically calibrated based on these computed values for providing absolute ICP level determinations. 
     Thus, provided in the system  401  according to a preferred embodiment is an optical coupling patch  402  and source/detector system  404  for providing a voltage signal V OUT  representing an instantaneous intensity of light collected at a detection port of the optical coupling patch  402 , in a manner similar to like elements of  FIG. 1 , supra. System  401  further comprises a console  406  comprising an output display  410  similar to the output display  120  of  FIG. 1 , supra, a user input device  412 , and a processor  414  configured and programmed to perform the functionalities described further herein. System  401  further comprises a mechanical vibrator  408  configured to apply a subsonic mechanical vibration to the skull of the patient  101 . Also shown in  FIG. 4A  is various external instrumentation equipment that is commonly available in a clinical setting, including a ventilator  496 , an EKG monitor  497 , a respiratory monitor  498 , and “other” device  499  that is capable of inducing and/or measuring some other form of intrinsic physiological oscillation or externally driven oscillation. The console  406  is coupled to receive V OUT  from the source/detector  404 , to receive a vibration frequency from the mechanical vibrator  408  (or to dictate such frequency to the mechanical vibrator  408 ), to receive a ventilation frequency or signal pattern from the ventilator  496 , to receive EKG signals from EKG monitor  497 , to receive respiratory signals from respiratory monitor  498 , and “other” signals from “other” monitor  499 . 
     Notably, many different combinations of the above-described elements  408 ,  496 ,  497 ,  498 , and  499  can be hooked up to the console  406  without departing from the scope of the preferred embodiments, including an option in which none of them are hooked up and only the signal V OUT  is provided to the console. Generally speaking, as more normative clinical data is gathered, the selected ones of these hookups providing the most useful signals will be identified, and increasingly precise results, even up to and including calibrated absolute ICP measurements, can be obtained. However, even in a simplest embodiment in which no external hookups are provided except for V OUT , the system  401  is still useful as an indicator as to whether the ICP is increasing, decreasing, or staying the same. Preferably, the processor  414  is configured to be easily upgradable, such as by firmware flash or internet download, so that the latest and best capabilities are integrated as more and more normative clinical data is gathered. 
     The user input device  412  allows a user, such as a clinician, to select the basis upon which non-invasive ICP measurement is to be made. Depending upon which buttons the user selects, the processor  414  will “listen” to the appropriate external signals, extract the relevant components from V OUT , and provide a best estimate P rel  (or, potentially, P absolute ) for display to the clinician. 
       FIG. 4B  illustrates a schematic diagram of the processor  414 , which can be implemented in any of a variety of physical configurations (e.g., in software general purpose processor, in hardware on application specific integrated circuit (ASIC), various combinations thereof, etc.) without departing from the scope of the preferred embodiments. Processor  414  comprises a bandpass filter  452  that is designed to extract a respiratory component C R  in a manner similar to the first processor  118  of  FIG. 1 , supra. The bandpass filter  452  is selected at switch SW 1  if the user has chosen neither the ventilator input nor the respiratory monitor input on the input device  412 . However, if the user has selected the ventilator or respiratory monitor option, then a lock-in detector  454  is selected at switch SW 1 , with a reference signal being from either the ventilator or respiratory monitor input via switch SW 2  per the user&#39;s selection. 
     As used herein, lock-in detector refers to a device or algorithm that receives an input signal and a periodic reference signal, and synchronously extracts frequency components from the input signal that correspond to the frequency content of the periodic reference signal. Generally speaking, if a periodic reference signal is available, lock-in detection is highly superior to passive bandpass filtering with respect to signal-to-noise performance, and so the processor  414  generates the signal C R  using the bandpass filter  452  as a “last resort” when the user has chosen neither the ventilator nor the respiratory monitor. However, the scope of the preferred embodiments is not so limited, and in other preferred embodiments, plural versions of the C R  signal can be generated using both the lock-in detector  454  and bandpass filter  452 , and both versions can be considered as distinct inputs to the evaluation module after envelope detection. It still another preferred embodiment, three versions of the C R  signal can be created, including one version from the bandpass filter  452 , a second version from the lock-in detector  454  using the ventilator reference signal, and a third version from the lock-in detector  454  using the respiratory monitor reference signal. 
     The signal C R , which is analogous to the periodic component signal C resp  of  FIG. 1 , supra, at plot  128 , is then fed to an envelope detector  464  for extracting the envelope signal E R , which is analogous to the distance between the envelopes  130   a / 130   b  of the plot  128  of  FIG. 1 . As discussed previously, the envelope signal E R  represents a measure of the intracranial matter compliance with respect to the respiratory oscillations of the patient. In another preferred embodiment (not shown), there is an option to turn off the respiratory channel entirely, in which case neither bandpass filter  456  nor the lock-in detector  458  is active and no respiratory component is input to the evaluation module  474 . 
     Processor  414  further comprises a bandpass filter  456  that is designed to extract a cardiac component C C  from the signal V OUT . The bandpass filter  456  is selected at switch SW 3  if the user has not chosen the EKG signal on the input device  412 . However, if the user has indeed selected the EKG signal, then a lock-in detector  458  is selected at switch SW 3 , with a reference signal being from the EKG output. The signal C C  is then fed to an envelope detector  470  for extracting the envelope signal E C , which represents a measure of the intracranial matter compliance with respect to the cardiac oscillations of the patient. In another preferred embodiment (not shown), there is an option to turn off the cardiac channel entirely, in which case neither bandpass filter  456  nor the lock-in detector  458  is active and no cardiac component is input to the evaluation module  474 . 
     Processor  414  further comprises a lock-in detector  460  that is designed to extract an externally driven vibratory component C V  from the signal V OUT . There is generally no need for a passive bandpass filter here because a reference signal should always be available, although the scope of the preferred embodiments is not so limited. The signal C V  is then fed to an envelope detector  466  for extracting the envelope signal E V , which represents a measure of the intracranial matter compliance with respect to the externally driven subsonic vibratory oscillations of the patient. The switch SW 5  is opened to turn off the subsonic vibratory oscillation channel if the user has not selected it on the input device  412 . 
     Processor  414  further comprises a lock-in detector  462  that is designed to extract an “other” oscillatory component C O  from the signal V OUT . Generally speaking, there may be a variety of other periodic inputs that could lead to corresponding intracranial matter oscillations, including those that are not yet currently known. By way of somewhat fanciful example, large periodic doses of therapeutic radiation might someday be applied that cause corresponding intracranial matter oscillations. The extraction of such “other” oscillatory components from the signal V OUT  and processing them to detect a metric of corresponding intracranial compliance is not outside the scope of the preferred embodiments. As illustrated in  FIG. 4B , the signal C O  is then fed to an envelope detector  468  for extracting the envelope signal E C , which represents such metric of corresponding intracranial compliance. The switch SW 4  is opened to turn off the “other” oscillation channel if the user has not selected it on the input device  412 . 
     Finally, evaluation module  474  receives those of E R , E V , E O , and E C  that are available according to the user&#39;s input and computes therefrom the output P rel  (or, potentially, P absolute ) for display on the display output  410 . Similar to the discussion supra with respect to  FIG. 1 , the particular algorithm by which a useful value for P rel  will be calculated can be determined, and continually improved, as further clinical data-gathering trials are completed and optimal statistical relationships determined. In one simple example, the percentage change in each of E R , E V , E O , and E C , and some average thereof, is monitored, and an output is provided that is assigned a decreasing value as that average increases and that is assigned an increasing value as that average decreases. Optionally, any of a variety of other outputs based on E R , E V , E O , or E C  can be provided in accordance with the gathered normative data. 
     It is to be appreciated that the scope of the preferred embodiments is not limited to the continuous wave scenario of FIGS.  1  and  4 A- 4 B. In another preferred embodiment (not shown), the emitting and detecting performed by the source(s) and detector(s) can be in accordance with phase modulation spectroscopy (PMS) or time resolved spectroscopy (TRS) principles, provided only that a one-dimensional signal (e.g., a time-varying voltage) representative of the detected output radiation (e.g. phase shift, time of flight, etc.) is provided to the first processor  118  ( FIG. 1 ) or processor  414  ( FIG. 4B ) that is at least partially dependent upon the intrinsic physiological oscillation(s) and/or an externally driven oscillation(s) in the patient. 
     In yet another preferred embodiment, (not shown), plural arrays of sources and detectors can be positioned and operated according to CWS, PMS, TRS, or other principles such that a two-dimensional map or image of a spatially varying property within the intracranial compartment is generated, the two dimensional image being time-varying and morphing, even if slightly so, according to the intrinsic physiological oscillation(s) and/or an externally driven oscillation(s) in the patient. Image processing can then be performed on the time-varying image to generate a metric related to an amount of morphing that is happening in correspondence with those oscillations. In one simple example, the amount of morphing can be identified as the time-varying distance between two landmark locations in the two-dimensional image. This metric can then be treated like the voltage V OUT  in  FIG. 1  or  FIG. 4 , supra, and the ICP variations can be computed therefrom as previously described. Notably, the particular physiological significance of the two-dimensional image (e.g., an oxygenation map, attenuation map, scattering map) will usually not be as important as the fact that it morphs measurably and in conjunction with the intrinsic physiological oscillation and/or externally driven oscillation in the patient. Advantageously, however, the two-dimensional image could be used for other useful purposes in conjunction with its use as a basis for ICP monitoring. 
       FIG. 5  illustrates non-invasive monitoring of ICP variations according to a preferred embodiment. At step  502 , optical radiation is introduced transcranially into the intracranial compartment. At step  504 , optical radiation is detected that has migrated through at least a portion of the intracranial compartment and back outward through the cranium. At step  506 , at least one signal representative of the detected optical radiation is processed to extract therefrom a component signal that varies in time according to one or more intrinsic physiological oscillations and/or one or more externally driven oscillations in the patient. Finally, at step  508 , the extracted component signal is processed to generate therefrom an output signal representative of the ICP variations in the intracranial compartment. 
       FIG. 6  illustrates a method for ICP monitoring in accordance with a preferred embodiment. At step  602 , an absolute ICP of a patient is monitored using an invasive ICP monitoring device such as a subarachnoid bolt. Although invasive ICP monitoring devices such as subarachnoid bolts are the gold standard for ICP measurement, their use can bring about infection or other negative consequences when left in the patient&#39;s skull for too long a period of time. According to a preferred embodiment, at step  604 , a non-invasive ICP monitoring device is placed in optical communication with the head of the patient while the invasive ICP monitoring device is still in the patient&#39;s skull. Preferably, the non-invasive ICP monitoring device uses optical radiation to transcranially detect variations in the magnitudes of periodic intracranial matter oscillations intrinsically and/or extrinsically induced, the magnitude variations being indicative of intracranial matter compliance variations brought about by ICP changes. At step  606 , the absolute ICP from the invasive ICP monitoring device is used to calibrate the non-invasive ICP monitoring device At a minimum, this can be used to establish a baseline output reading for the non-invasive unit in absolute mm Hg, for cases in which the patient&#39;s ICP remains constant during the simultaneous monitoring. On the other hand, if the patient&#39;s ICP fluctuates during simultaneous monitoring, a more complete multi-point calibration of the non-invasive unit can be achieved that will be accurate at least within the range of fluctuation that has occurred, and possibly beyond that range if normative data from clinical data-gathering trials dictates that some degree of extrapolation can safely occur. At step  608 , the ICP monitoring device is removed, which can be triggered by the normal course of a therapeutic intervention, or which alternatively be triggered by a determination that sufficient calibration of the non-invasive ICP monitor has been achieved. Finally, at step  610 , ICP monitoring is continued by maintaining the non-invasive ICP monitoring device in optical communication with the head of the patient. 
       FIG. 7  illustrates conceptual time plots corresponding to a method for ICP monitoring according to another preferred embodiment in which an “impulse response” of the intracranial matter, as measured by a transient effect on the detected optical signal(s) induced by a discrete mechanical impulse on the head of the patient, is monitored over time. For this embodiment, the mechanical vibrator  408  of  FIG. 4 , supra, is replaced by a mechanical thumper (not shown). The mechanical thumper can be, for example, a pre-calibrated spring-loaded plunger that delivers known impulses (force thumps) to the skull of the patient, or another type of mechanical transducer having similar effect. The mechanical thumper can operate in a recoil-based manner (analogous to a recoil hammer that bounces back after striking) or in a non-recoil-based manner (analogous to a deadblow hammer that does not bounce back after striking) without departing from the scope of the preferred embodiments. 
     Referring again to  FIG. 7 , using the mechanical thumper, a plurality of discrete mechanical impulses  700 ,  701 , and  702  are applied to the head of the patient at a respective plurality of discrete points in time t 0 , t 1 , and t 2 . The time spacing among the time points t 0 , t 1 , and t 2  can be on the order of seconds or minutes and is not required to be constant, although the scope of the preferred embodiments is not so limited. Indeed, the time between impulses can even be dynamically variable, for example, at reduced intervals when the ICP is varying relatively quickly with time. 
     During each of a plurality of time intervals (INT 0 , INT 1 , INT 2 ) immediately subsequent to each respective discrete point in time (t 0 , t 1 , t 2 ) optical radiation is applied to the patient that propagates transcranially into the intracranial compartment, and optical radiation that has migrated transcranially outward from the intracranial compartment is detected. A plurality of time signals (W TRANS,0 (t), W TRANS,1 (t), W TRANS,1 (t)) representative of the optical radiation detected during the respective time intervals (INT 0 , INT 1 , INT 2 ) is then processed to generate an output signal representative of the ICP variations. 
     For one preferred embodiment, the processing comprises, for each of the time signals (W TRANS,0 (t), W TRANS,1 (t), W TRANS,1 (t)), computing at least one transient characteristic thereof induced by the mechanical impulse ( 700 ,  701 ,  702 , respectively) associated therewith. Preferably, on an impulse over impulse basis, a decreasing value is assigned for the ICP output signal when the computed transient characteristic(s) change toward values indicative of greater intracranial matter compliance, while an increasing value is assigned for the ICP output signal when the computed transient characteristic(s) change toward values indicative of lesser intracranial matter compliance. For a particular time signal W TRANS,j (t), examples of transient characteristics can be the peak difference between W TRANS,j (t) and the steady state value W SS  (i.e., the value or characteristic when there has been no thumping for a substantial time), the time-to-peak or rise time after the impulse, the overall time center of mass of the curve W TRANS,j (t), the relaxation time between the peak value at the steady-state value, or any of a variety of other transient characteristics that characterize how much and/or how fast the intracranial matter is shaking, shifting, etc. responsive to the mechanical thumping. Generally speaking, the best type of optical modulation/filtering scheme used to derive W TRANS,j (t), the type and degree of thumping, the particular selection and/or combinations to transient characteristics to compute, the particular manner in which those values are calibrated to relative or absolute ICP metrics, and other relevant factors could be determined by a person skilled in the art (e.g., empirically using structured clinical experiments) in view of the present disclosure without undue experimentation. 
     Whereas many alterations and modifications of the preferred embodiments 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. Thus, reference to the details of the described embodiments are not intended to limit their scope.