WO2005055815A2 - Systems and methods for dynamic analysis of muscle function and metabolism - Google Patents

Abstract

The present invention provides systems and methods for correlating dynamic muscle function and metabolism as a comprehensive approach to analyzing localized muscle physiology. In one aspect, the invention provides systems and methods for measuring and analyzing muscle force production and tissue metabolism. In one aspect, these are simultaneously monitored during isotonic muscle movements as an assessment of muscle physiology. In one aspect, the invention provides systems and methods for measuring changes in reflected and/or attenuated spectral features of whole blood in tissues before, during and after performance of repetitive tasks.

Description

SYSTEMS AND METHODS FOR DYNAMIC ANALYSIS OF MUSCLE FUNCTION AND METABOLISM

Technical Field The present invention relates generally to systems and methods for analyzing dynamic muscle function and muscle metabolism as a comprehensive approach to studying localized muscle physiology. In one aspect, localized dynamic muscle function and muscle metabolism are analyzed. More particularly, in one embodiment the invention relates to the analysis of muscle force production and tissue metabolism, which are simultaneously monitored during isotonic muscle movements as an assessment of muscle physiology. In one aspect, the invention provides systems and methods for measuring localized changes in reflected and/or attenuated spectral features of whole blood in tissues before, during and after performance of repetitive tasks.

Background Muscle physiology is extremely complex, in part because muscle movement involves the concerted action of many different cell types. Muscles themselves can be extremely short or extremely long, and their architecture varies tremendously. Muscles are organized into individual fibers, which in turn are organized into bundles, which are joined together at each end to a tendon to form individual groups, or simply "muscles". Each fiber, bundle and group is surrounded by a specialized layer of connective tissue forming a complex lattice between muscle cells. Each muscle cell contains all of the normal cellular components. Most notably, as with nearly all cells, muscle cells contain mitochondria which are the organelles that consume oxygen to form the energy necessary to contract. The capillary system physically links muscle cells to the cardiovascular system, and acts as the conduit for the supply of oxygen from the lungs. Muscle fibers contribute to force production when they are "recruited" by the brain. In particular, the nervous system consists of thousands of individual branches that terminate in muscle fibers to form motor units. Each motor unit contains close to one thousand individual fibers, which can be either type I (slow twitch) or type II (fast twitch) fibers.

Whereas each motor unit consists of only one type of fiber, each muscle is a heterogeneous mixture of both. Muscles produce force in proportion to the amount of activity. Smaller motor units are recruited first, and have a low threshold for activation. When more force is necessary to carry out an activity, larger motor units are recruited. When force requirements are relatively low, such as with using a keyboard, smaller motor units consisting mainly of slow twitch fibers are principally involved. In unfatigued muscles, a sufficient number of motor units will be recruited to supply the necessary force. Initially, this may be accomplished with very little involvement of fast motor units. However, as muscles become fatigued, fast units will be recruited as the brain attempts to maintain the desired force production. As a result, a fatigued muscle will require a greater number of motor units to produce force, which in turn accelerates the fatigue process and results in the production of lactic acid which causes pain. The impairment of normal muscle physiology, which causes muscle pain, weakness and/or fatigue, can be associated with various disease states, such as circulatory problems, arthritis, infections, etc. In addition, muscle impairment, and especially fatigue, can be "self-induced", such as that observed in professional athletes, as well as individuals whose daily activities involve repetitive tasks. The latter results in what is commonly referred to as "repetitive stress injuries" or "RSI". Repetitive stress injuries (RSIs) are a major clinical problem in today's society. Millions of people are affected with varying degrees of RSI. In addition to the pain associated with this condition, the economic impact of managing patients with RSI is significant.

Although keyboard usage is most often associated with RSI, other repetitive movements may also be causative. For example, use of a computer mouse, joystick, cooking utensils, musical instruments, and other repetitive movements found in home and industrial settings involving repetitive movements of, e.g., hands, arms, feet, legs), may also cause RSI. In addition, although repetitive movements are the primary cause of injury, other factors may play an important role in the onset and progression of this condition. For example, RSI can also be associated with a traumatic incident, hypothyroidism, diabetes mellitus, various arthropathies and obesity (S. G. Atcheson, et al., Archives of Internal Medicine, 158(14): 1506-1512 (1998)). One of the most common forms of RSI is carpal tunnel syndrome (CTS). The major cause of CTS is believed to be repetitive movements of the fingers and wrist. CTS is generally characterized by numbness, tingling, pain and weakness, as well as edema. One characteristic finding in CTS patients is the involvement of the fingers innervated by the median nerve. It is thus generally believed that CTS involves some form of nerve compression or inflammation of the median nerve in the wrist area where the carpal tunnel resides. While performing repetitive movements, CTS patients exhibit a decrease in the production of force associated with the onset of pain which is not only localized in the hand, but also in the forearm, elbow and shoulder. CTS diagnosis is a complex and somewhat controversial process. Many researchers diagnose CTS on the basis of clinical findings alone (J. H. Anderson, et al, J.A.M.A., 289: 2963-2969 (2003)). However, others believe that objective measurements such as nerve conduction studies must also be considered (P. A. Nathan, et al, J.A.M.A., 290(14): 1853-1854 (2003)). Treatment of CTS usually involves releasing pressure on the median nerve in the area of the carpal tunnel. However, many post-surgical patients continue to have symptoms, and relatively few are able to return to the exact same work environment (F. Destefano, et al, J. Hand Surg. Am. 22: 200-210 (2003)). Various methods have also been described for monitoring fatigue. For example, U.S. Patent No. 5,349,963 describes that the fatigue level of a particular muscle is determined from electromyographic (EMG) signals that are measured from that muscle. EMG signals may be employed to detect muscle fatigue while the muscle undergoes isometric- or isotonic-type testing. During isometric contraction, muscles contract without any observable change in length, whereas during isotonic contraction, muscles change length during contraction. For isometric-type testing, electrodes are attached to a muscle being studied and the test subject is instructed to apply a constant force with that muscle while maintaining that muscle in a static position. For isotonic-type testing, electrodes are attached to a muscle being studied and the test subject is instructed to perform multiple cycles of repetitive motions with that muscle. In both types of testing, EMG signals, which are measurements of muscle output activity, are collected for fatigue analysis. Methodologies have also been described for measuring the amount of force generated by a muscle or group of muscles. For example, in U.S. Patent No. 5,579,238 and U.S. Patent No. 5,745,376, the force that a user applies to a keyboard is measured. Feedback is provided to the user when excessive force is detected so that the user can reduce the force applied to the keyboard and thereby reduce the likelihood of developing RSI. In U.S. Patent No. 5,579,238, fmger force is measured by way of a vibration detecting device attached to the keyboard. The signals from the vibration sensor are proportional to the force produced by the fingers. The force data is used to trigger auditory warning signals if the force exceeds a certain threshold level. In U.S. Patent No. 5,745,376, an initial force is compared with a secondary force. If the secondary force is larger than the initial force, the system triggers an auditory warning signal. U.S. Patent No. 5,885,231 describes the measurement of force to study motor deficit for the purpose of diagnosis and treatment monitoring. In addition, U.S. Patent No. 6,352,516 and U.S. Patent Application Serial No. 09/819,183, each describe systems and methods for measuring muscle forces during isotonic, repetitive movements, as a means for, e.g., monitoring the onset of fatigue. However, none of the aforementioned references discuss the dynamic analysis of both muscle function and metabolism. In order to contract and produce force, muscles (and other tissues) derive their energy through metabolic pathways. There are two principle types of metabolism: anaerobic and aerobic. Anaerobic metabolism refers to the production of energy in the absence of oxygen. This involves the glycolitic pathway for the production of energy in the form of adenosine triphosphate (ATP). Each cycle of this pathway produces two molecules of ATP. In contrast, the aerobic pathway, which involves oxidative phosphorylation, produces 36 molecules of ATP. Accordingly, muscles are much more efficient at producing energy in an oxygen-rich environment. The ability of muscles to produce energy depends, in part, on the efficiency with which oxygen is supplied to "working" muscles. This involves the concerted action of the lungs, and their efficient delivery of oxygen to hemoglobin, which serves as the principle oxygen carrier for the circulatory system. Once it reaches the microcapillary system, oxygen becomes dissociated from oxygenated hemoglobin (also called oxyhemoglobin, or "HbO "). Deoxygenated hemoglobin, or deoxyhemoglobin is thus formed, and the dissociated oxygen is then free to diffuse into muscle cells. Once it becomes intracellular, it enters the mitochondria within the cells where the oxidative phosphorylation process, also called "aerobic respiration", takes place. Systems and methods for measuring changes in whole blood metabolite concentrations have previously been described. See, e.g., U.S. Patent No. 5,879,294. Therein, the patentees describe the analysis of spectral data from tissues such as cerebral tissue or the heart. Additionally, U.S. Patent Application No. 2003/0088163 describes the measurement of partial oxygen pressure and pH as indicators of tissue oxygenation. However, these technologies have not been previously adapted for use in correlating dynamic changes in metabolite concentration with muscle function, such as the performance of repetitive tasks. Accordingly it would be desirable to have a system that could perform such studies as a more comprehensive way of evaluating localized muscle physiology.

SUMMARY OF INVENTION The invention provides systems and methods for the analysis of metabolism (e.g., by oxygen utilization) by muscles during performance of physical activities (i.e., muscle function), thus providing a dual-approach to the study of muscle physiology. This dual- approach systems and methods of the invention are more useful from both a diagnostic and therapeutic perspective measuring muscle metabolism or function alone. When muscular responses are compromised due to disease states or fatigue, the utilization of oxygen by these muscles will be affected. For example, when oxygen metabolism in leg muscles is monitored while an individual is on a treadmill, as the muscles become fatigued, they convert progressively less oxygen to carbon dioxide. The present invention relates to systems and methods for studying muscle physiology comprising means for monitoring muscle metabolism over time and means for monitoring muscle function over time. The means for monitoring muscle metabolism may be selected from the group consisting of. a skin sensor for measuring skin-secreted muscle-related analyte concentration; an apparatus for measuring blood or skin pH; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration in a bodily fluid; a near infrared spectroscopy system for measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, hematocrit, tissue water content; and an apparatus for measuring skin or body temperature. The means for monitoring muscle function may be selected from the group consisting of. a force measuring system for measuring a force profile; an acceleration measuring system for measuring acceleration of system members in a plane upon which force is applied; a blood pressure monitor; a heart rate monitor; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration; and an electromyelogram device. The system may further comprise means for correlating data produced by the means for monitoring muscle metabolism function and the means for monitoring muscle function, such as a computer. The present invention also relates to systems and methods for monitoring muscle fatigue by measuring acceleration profiles of a body part, such as the fingers, as muscles are contracted. For example, the invention provides a method for measuring muscle fatigue of a subject comprising instructing the subject to apply repetitive force to an apparatus, wherein the apparatus has an accelerometer functionally attached thereto for generating an acceleration profile; and monitoring the acceleration profile over time during application of the repetitive force. In such case, muscle fatigue or other muscle-related conditions are evaluated by measuring acceleration profiles of a body part, such as the fingers, as muscles are contracted. The invention provides systems for analyzing or studying muscle physiology comprising: an apparatus for monitoring muscle metabolism over time; and, an apparatus for monitoring muscle function over time. The invention provides systems for analyzing or studying muscle physiology comprising: means for monitoring muscle metabolism over time; and, means for monitoring muscle function over time. In one aspect, the apparatus or means for monitoring muscle metabolism is selected from the group consisting of: a skin sensor for measuring skin-secreted muscle-related analyte concentration; an apparatus for measuring blood or skin pH; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration in a bodily fluid; a near infrared spectroscopy system for measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, hematocrit, tissue water content; an apparatus for measuring skin or body temperature; and, a combination thereof. In one aspect, the apparatus or means for monitoring muscle function is selected from the group consisting of: a force measuring system for measuring a force profile; an acceleration measuring system for measuring acceleration of system members in a plane upon which force is applied; a blood pressure monitor; a heart rate monitor; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration; an electromyelogram device; and a combination thereof. In one aspect, the systems or methods of the invention further comprise an apparatus or device for correlating data produced by the apparatus or means for monitoring muscle metabolism function and/or the apparatus or means for monitoring the muscle function. The data can correlated using a computer-run program, e.g., including a computer. In one aspect, muscle function monitoring comprises monitoring isotonic muscle movements. In one aspect, the muscle function monitoring comprises monitoring of a single muscle or a set of muscles, e.g., the muscle function monitoring comprises simultaneously monitoring all the muscles in a hand, a leg, or an arm. In one aspect, the systems can further comprising an ergonomic keyboard for generating finger force profiles. The invention provides methods for analyzing or studying muscle physiology comprising: monitoring muscle metabolism over time; and, monitoring muscle function over time. In one aspect, the muscle metabolism is monitored by a skin sensor for measuring skin- secreted muscle-related analyte concentration; an apparatus for measuring blood or skin pH; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration in a bodily fluid; a near infrared spectroscopy system for measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, hematocrit, tissue water content; an apparatus for measuring skin or body temperature; or, a combination thereof. In one aspect, the muscle function is monitored by a force measuring system for measuring a force profile; an acceleration measuring system for measuring acceleration of system members in a plane upon which force is applied; a blood pressure monitor; a heart rate monitor; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration; an electromyelogram device; or, a combination thereof. In one aspect, the method comprises use of an ergonomic keyboard for generating finger force profiles. In one aspect, the muscle metabolism over time and the muscle function over time are simultaneously monitored, or, muscle function is measured at one time and muscle metabolism is measured at another time under the same or similar conditions. In one aspect, the muscle function monitoring comprises monitoring isotonic muscle movements. The muscle function monitoring can comprise monitoring of a single muscle or a set of muscles. The muscle function monitoring can comprise simultaneously monitoring all the muscles in a hand, a leg, or an arm. In one aspect, the systems or methods can further comprise correlating the muscle metabolism over time data and the metabolism function over time data. The data can be correlated using a computer-run program, e.g., by a computer. The invention provides methods for measuring muscle fatigue of a subject comprising: (a) instructing the subject to apply repetitive force to an apparatus, wherein the apparatus has an accelerometer functionally attached thereto for generating an acceleration profile; and (b) monitoring the acceleration profile over time during application of the repetitive force. The invention provides methods for measuring changes in reflected or attenuated spectral features of whole blood in tissues before, during and/or after performance of repetitive tasks in a subject comprising: (a) instructing the subject to apply repetitive force to an apparatus, wherein the apparatus has an accelerometer functionally attached thereto for generating an acceleration profile; and (b) monitoring the reflected or attenuated spectral features in the whole blood in the tissues of the subject before, during and/or after performance of the repetitive tasks. The invention provides methods for diagnosing or assessing carpal tunnel syndrome (CTS) in an individual, comprising the steps of: monitoring muscle metabolism over time; monitoring muscle function over time; and, monitoring pain, wherein CTS patients exhibit a decrease in muscle function associated with the onset of pain localized in the hand, forearm, elbow or shoulder. In one aspect, the muscle metabolism is monitored by a skin sensor for measuring skin-secreted muscle-related analyte concentration; an apparatus for measuring blood or skin pH; a blood analyte analyzer capable of measuring a muscle- related blood analyte concentration in a bodily fluid; a near infrared spectroscopy system for measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, hematocrit, tissue water content; an apparatus for measuring skin or body temperature; or, a combination thereof. In one aspect, the muscle function is monitored by a force measuring system for measuring a force profile; an acceleration measuring system for measuring acceleration of system members in a plane upon which force is applied; a blood pressure monitor; a heart rate monitor; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration; an electromyelogram device; or, a combination thereof. In one aspect, the muscle metabolism over time and the muscle function over time are simultaneously monitored during isotonic muscle movements. In one aspect, the methods further comprise correlating the muscle metabolism over time data and the metabolism function over time data, which can be done, e.g., by a computer. The invention provides methods for facilitating diagnosis of a muscle pathology in a subject comprising the steps of monitoring metabolism of a muscle or a group of muscles over a set period of time, monitoring function of these muscles over the set period of time, determining a correlation between the metabolism and the function of the muscle or a group of muscles, wherein if the relationship between the metabolism and the function is not within a normal range for the same muscle or a group of muscles a diagnosis of a particular pathology can be facilitated. In one aspect, the facilitated diagnosis comprises analysis of localized muscle physiology in a diabetic patient. The invention provides articles, e.g., computer program products, comprising a machine-readable medium including machine-executable instructions, computer systems and computer implemented methods to practice the methods of the invention, e.g., for reading, collating, correlating, displaying and/or storing data produced by apparatus used in the systems and methods of the invention, e.g., for monitoring muscle metabolism function and/or for monitoring muscle function; for diagnosing a muscle disease or dysfunction; for ascertaining the effectiveness of various strength developing devices; to study the effects of repetitive movement of any body part, such as the elbow, knee, foot, torso, etc.; to study the effectiveness of ergonomic aids, and the like. Other aspects of the invention are described elsewhere herein. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. All publications, patents and patent applications cited herein are hereby expressly incorporated by reference for all purposes.

Brief Description of the Drawings The invention is described in detail herein with reference to the following drawings of exemplary embodiments in which: Figure 1 is a schematic diagram illustrating the basic elements of a person's arm that work together to generate finger forces. Figure 2 represents sample EMG outputs of a subject performing repetitive motions. Figure 2A depicts the relationship between EMG signal (RMS) and time, and Figure 2B depicts the relationship of EMG signal amplitude/frequency and time. Figure 3 A is an illustration of an ergonomic keyboard for the left hand for generating finger force profiles that are used to monitor fatigue using an FMS. Figure 3B is an illustration of a force measuring system for fingers, including an ergonomic keyboard for the right hand, for generating finger force profiles that are used to monitor fatigue. Figure 4 is a detailed illustration of one of the keys on the ergonomic keyboard of Figure 3 A. Figure 5 is a block diagram of a combined force measuring system, including hardware, software and a keyboard, for monitoring the onset of finger fatigue. Figure 6 is a schematic illustration of a digital signal processing circuit for the keyboard switches arranged on the ergonomic keyboard of Figure 3 A. Figure 7 is a schematic illustration of an analog signal processing circuit for the force sensors arranged on the ergonomic keyboard of Figure 3 A. Finger 8 illustrates side (8A) and top (8B) views of a calibrator used for the fmger force sensors. Figure 9 is a sample display that provides visual feedback of the forces generated by the subject while the subject is being monitored for fatigue with the keyboard of Figure 3A. Figures 10A-10E are sample force production profiles for each of the fingers on a test subject's hand as follows: lOA-thumb, lOB-index finger, lOC-middle finger, lOD-ring finger, and lOE-little finger. Figure 11 graphically depicts the force production profile (solid line) superimposed with the force effect profile (dotted apparatus line) generated using the depicted in Figure 8. Figure 12 is an illustration of a force measuring system incorporated into a personal computer system that includes a mouse and joystick. Figure 13 is an illustration of a force measuring system which also includes means for measuring EMG. > Figure 14 is a graphical depiction of the instrumental readings using the NIRS apparatus described in the EXAMPLES. Event marker 1 represents baseline measurements; event marker 2 represents the beginning of the performance of the repetitive task; event marker 3 represents cessation of the task; event marker 4 represents the end of the study. A = StO₂; B = Deoxyhemoglobin; C = Total hemoglobin concentration; D = Oxyhemoglobin; and E = hematocrit. Figure 15 is a graphical depiction of the data obtained with a normal subject's dominant (right) side, as described in the EXAMPLES. Figure 16 is a graphical depiction of the same data described in Figure 15 with a normal subject's non-dominant (left) side. Figure 17 is a graphical depiction of the data obtained with a CTS patient's affected (right) side as described in the EXAMPLES. Figure 18 is a graphical depiction of the data obtained with a CTS patient's non- affected (left) side as described in the EXAMPLES.

DETAILED DESCRIPTION The invention provides systems and methods for analyzing or studying dynamic muscle function and muscle metabolism as a comprehensive approach to studying muscle physiology. The analysis can be a total body analysis, or, localized. For example, in one aspect, the systems and methods of the invention analyze dynamic localized muscle function (e.g., an arm, a leg, a hand, a finger) and muscle metabolism to study localized muscle physiology. The invention's approach allows for the determination of the relationship between muscle activity at the organ level (muscle function) and the cellular level (muscle metabolism) over time. If this relationship does not follow the established normal patterns for the muscle function and metabolism under study, then the diagnosis of a particular pathology can be facilitated and treatment interventions and protocols can be designed and monitored for efficacy. The analysis of muscle metabolism according to the present invention includes, inter alia, the measurement of metabolite fluctuations that are produced during muscle use. The analysis of muscle function according to the present invention includes, inter alia, biomechanical measurements of muscle function, e.g. movement and force dynamics, as well as electrical measurements of muscle contraction via electromyography. Each of these two components, as well as other aspects of the present invention, will be described in more detail below. In one embodiment, muscle metabolism and function are monitored simultaneously. However, it is possible to monitor muscle function at one time and muscle metabolism at another time under the same or similar conditions. In either case, the two studies are converted to data (e.g., numerical or graphical) and preferably correlated to one another using a mathematical algorithm adapted to determine the relationship between the two and to distinguish between normal and abnormal results. This dual mode approach to studying muscle metabolism allows for a much more efficient evaluation of abnormal or pathological conditions. In one embodiment, systems and methods are described for measuring muscle metabolism while isotonic muscle movements are evaluated. In another embodiment, the invention relates to systems and methods for measuring changes in reflected and/or attenuated spectral features of whole blood in muscles (or sunounding tissues) before, during and after performance of repetitive movements by target muscle groups. (As used herein, the term "repetitive" refers to both the same motion produced by the same body part, or the same motion produced by different body parts in sequence. For example, it refers both to tapping the same finger repeatedly and also to tapping all four fingers sequentially.) Muscle Metabolism Generally Muscle metabolism is a complex process involving a cascade of extra- and intra-cellular events that eventually leads to the production of force when the brain signals the muscles to contract. Muscle metabolism can be measured by a number of different methods, which are indirect or direct, and can also be either localized or generalized. As used herein, the term "muscle metabolism" is intended to refer to metabolic events that take place in muscle cells themselves, in the surrounding tissue cells (such as the connective tissues), or in the extracellular spaces surrounding these cells (such as the circulatory system). It is a well known fact that the metabolic activity of cells causes changes in the localized concentration of various chemical substances over time. Such concentration changes can be exhibited intracellularly and/or extracellularly. In addition, there is a close tie between metabolic activity and blood flow in the body, especially in muscle tissues. During muscle contraction, which is tied to changes of neuronal activity in the brain, there is an increase in blood flow. Actively metabolizing cells release vasoactive substances that cause vasodilation, which functions to ensure that the tissues are adequately supplied by oxygen, and that the byproducts of metabolism, such as carbon dioxide, hydrogen ions and lactic acid, are removed. This necessarily results in detectable localized changes in the concentration of many different chemical substances over time. The invention provides detection of such changes, and detection of changes in many substances locally or systemically. The changes can be inferred from monitoring systemic changes, such as changes in metabolite concentrations in the peripheral blood system or other bodily fluids. For example, blood pressure and heart rate are indirect indicators of muscle metabolism, since blood pressure and heart rate predictably change as a person utilizes their muscles and the muscles produce energy. Local measurements include the use of skin sensors to monitor fluctuations in metabolites during muscle use. For example, such sensors are useful for determining whether the working muscle is exhibiting anaerobic or aerobic respiration. Anaerobic respiration results in a faster increase in lactic acid concentrations than aerobic respiration. Accordingly, in some aspects skin sensors are used, e.g., where they are capable of measuring lactic acid levels to determine the efficiency of muscle metabolism. In one embodiment, fluctuations in localized oxygen concentration are measured as an indicator of muscle metabolism. However, other cellular components, such as proteins, cellular metabolites and ions can also be measured, either directly or indirectly, instead of or in addition to oxygen. The following is a representative (exemplary) list of metabolites are measured in alternative aspects of the invention: Adenosine. Adenosine is formed form cellular AMP, which is derived from hydrolysis of intracellular ATP and ADP. Adenosine formation increases during hypoxia and increased oxygen consumption. Enzymes. Enzymes play an important role in the production of energy. For example, myokinase catalyzes the production of ATP from ADP. In addition, creatine kinase transfers phosphate ions form creatine phosphate to ADP to form ATP and creatine. Potassium or sodium ions. Sodium ions are taken up and potassium ions are released by contracting muscles. Normally, ionic gradients stay fairly constant, but during muscle contractions, small increases in extracellular potassium can accumulate. Carbon dioxide. During increased oxidative metabolism, as oxygen is depleted, carbon dioxide is formed. Hydrogen ions. Hydrogen ion concentration increases when carbon dioxide increases, or during states of increased anaerobic metabolism. Lactic acid. Lactic acid is another product of anaerobic metabolism. Inorganic phosphate. Inorganic phosphate is released by the hydrolysis of ATP and ADP. Cytochromes. Cytochromes, such as cytochrome A3, play a role in mitochondrial metabolism. More particularly, cytochrome A3 is necessary to produce ATP and thus energy, by combining with oxygen. Water. Water, usually in the form of interstitial fluid, is a normal byproduct of cellular metabolism. However, an excess of water in the tissues, i. e. edema, is often an 'indicator of a pathological condition associated with abnormal cellular metabolism. Others. In addition, muscle metabolism may be measured by means of monitoring hematocrit, hemoglobin saturation curves, nitric oxide binding characteristics, nitrosyl hemoglobin concentration, and other mitochondria-associated metabolic functions. In addition to the above measurements, skin temperature also can be monitored as an indicator of muscle metabolism. Methods of measuring skin temperature are well known in the art and include the use of infrared cameras. In general, skin temperature is controlled by blood flow. With certain pathological conditions such as CTS, there is an observable decrease in skin temperature in the affected hand that does not ablate during repetitive movements by the fingers. This indicates that the physiological mechanisms that control blood flow may be compromised in such conditions. Accordingly, in one aspect, measurement of skin temperature is used in the practice of the present invention for analyzing muscle metabolism. Oxygen Metabolism Specifically In one embodiment, oxygen concentration is measured indirectly by measuring the combined concentration of oxygenated hemoglobin, myoglobin, or a combination of the two. Measurement of oxygen in the form of oxygenated hemoglobin, or oxyhemoglobin, is also referred to as measuring "hemoglobin oxygen saturation". Decreases in hemoglobin oxygen saturation are thus indicative of utilization of oxygen by muscles. Hemoglobin and myoglobin are both heme proteins that bind oxygen. Myoglobin is a monomeric protein found mainly in muscle tissue which serves as an intracellular storage site for oxygen. Hemoglobin, on the other hand, is a tetrameric protein found mainly in red blood cells. The oxygen earned by both hemoglobin and myoglobin is bound to the ferrous ion (Fe2+) of the heme group. When the ferrous ion is oxidized to a ferric ion (Fe3+), it is no longer capable of binding oxygen and the oxygen becomes dissociated. Although the basic structure of hemoglobin subunits and myoglobin are similar, variations in their amino acid composition and overall structure markedly influence their oxygen carrying properties. Hemoglobin consists of four separate subunits - two alpha subunits and two beta subunits. Myoglobin consists of a single subunit and is most similar to hemoglobin's alpha-subunits. Comparison of the oxygen binding properties of myoglobin and hemoglobin demonstrate the "allosteric" properties of hemoglobin - the oxygen binding curve of hemoglobin is sigmoidal. When oxygen binds to the first subunit of deoxyhemoglobin, it increases the affinity of additional oxygen to bind. As additional oxygen is bound to the second and third subunits, oxygen binding is further strengthened. As oxyhemoglobin unloads its oxygen in the tissues, the oxygen affinity incrementally decreases. Low affinity, deoxygenated hemoglobin, is referred to as being in the taut (T) state, whereas fully oxygenated hemoglobin, oxyhemoglobin, is referred to as being in the relaxed (R) state. In contrast to hemoglobin, myoglobin' s single subunit exhibits a simple hyperbolic oxygen saturation curve. Metabolism Measurements Oxygenation: In one aspect, the metabolism measurement of the systems or methods of the invention comprise measurement of oxygenation of a muscle tissue using, e.g., a near-infrared spectroscopy (LAIRS) or an equivalent device, as described, e.g., in U.S. Patent No. 5,879,294; 5,515,864; 5,593,899; 5,931,799; 6,015,969; 6,123,597; or 6,216,021. The near infrared spectrum exhibits an absorption band at 850 nm when hemoglobin and myoglobin are oxygenated, and an absorption band of 760 when they are deoxygenated. Accordingly, an absorption band shift from 850 to 760 indicates oxygen utilization. Since most of the near- infrared signal is believed to originate from hemoglobin and not from myoglobin, changes in signal mainly measure changes in vascular oxygen levels. Near-infrared spectroscopy (LAIRS) has previously been described for use in monitoring hemoglobin/myoglobin oxygen saturation fluctuations during exercise. See, e.g., U.S. Patent No. 5,879,294. Such techniques are useful for measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin and/or hematocrit. As oxygen saturation decreases, which suggests that oxygen is being utilized by the muscles, deoxyhemoglobin levels increase and oxyhemoglobin levels decrease. Interestingly, the hematocrit is observed to decrease during exercise, suggesting that either the muscle contraction and/or vasoconstriction decreases the number of red blood cells in the muscle's vasculature. Other patents that describe optical methods for measuring oxygen saturation include, e.g., U.S. Patent No.s 5,515,864; 5,593,899; 5,931,799; 6,015,969; 6,123,597; and 6,216,021. In addition, Hutchinson Technology, Inc. (Hutchinson, Minnesota) and Somanetics Corporation (Troy, Michigan) each sell LAIRS devices for measuring oxygen saturation which are modifiable as described elsewhere herein for use in the practice of the present invention. In one embodiment, NIBS is utilized to measure oxygen concentration during muscle use. Previous studies have been undertaken to use LAIRS to evaluate muscle oxygenation trends during exercise. See, e.g., Y. Bhambhani, et al, Medicine and Science in Sports and Exercise, 31 (l):90-98 (1999). Therein, the authors describe a linear increase in oxygen uptake during isometric exercise. However, they also report that their method was not sensitive enough to predict the amount of oxygen extracted by the muscles during exercise. Water: In one aspect, the metabolism measurement of the systems or methods of the invention comprise measurement of water in a muscle tissue using, e.g., a near-infrared spectroscopy (LAIRS) or an equivalent device. In addition to measuring oxygen concentration as described above, NIRS can also be used to detect the amount of water in the tissues as a means for evaluating muscle metabolism. Hydrogen Ions: In one aspect, the metabolism measurement of the systems or methods of the invention comprise measurement of hydrogen ions of a muscle tissue using, e.g. a near-infrared spectroscopy (LAIRS) or an equivalent device. Hydrogen sensors are known in the art and can also be used to measure hydrogen levels in tissues locally as another means for evaluating muscle metabolism. Muscle Function Generally In one aspect, the metabolism measurement of the systems or methods of the invention comprise measurement of the general muscle function of a muscle tissue. The other necessary component of the systems and methods of the present invention is the dynamic analysis of localized muscle function. Accordingly, a muscle group or groups is/are targeted for analysis. When a subject is instructed to contract the muscle(s), muscle function is assessed either directly or indirectly over a period of time. Monitoring muscle function directly includes, for example, monitoring force (mass X acceleration). Alternatively, muscle function can be analyzed by monitoring acceleration, displacement or velocity alone or in combination with one another. Such analyses are performed while monitoring the movement of a subject's limbs or other body parts in a plane or other complex space during muscle contraction. For example, monitoring acceleration of the fingers as they depress keys on a keyboard in and of itself is a good way of monitoring muscle fatigue in patients with RSI such as carpal tunnel syndrome (CTS). Such measurements are made by adapting the force measuring system (FMS) described herein to monitor acceleration alone by replacing the force sensors with accelerometers. Indirectly, muscle function can be monitored by analyzing the electrical impulses produced by contracting muscles, such as with an electromyelogram (EMG). These and other methods are described in the literature and can easily be carried out by one of skill in the art. Force Production and Analysis The present invention provides a force measuring system (FMS) that is useful for evaluating muscle function, e.g., muscle fatigue. When adapted for the evaluations of repetitive finger motions, it can be used to detect, avoid, and/or treat carpal tunnel syndrome (CTS). When studying repetitive activities involving fingers, many factors may influence the generation of finger force, such as the activity of the muscles and the tendons shown in Figure 1, but the end result of finger activation is force produced by the fingers. As a person fatigues while performing repetitive finger motions, EMG signal amplitude from the muscles (which can be measured in terms of root mean square (RMS)), tends to increase while the time it takes to perform the motion tends to decrease. See Figure 2A. In addition, as the amplitude of the EMG signals increase, the frequency of the EMG signals decrease. See Figure 2B. These EMG signal changes can be evaluated simultaneously with force measurements to enhance the ability to obtain useful clinical information from the EMS. The EMS according to one embodiment of the invention is illustrated in

Figure 3 A. It shows an ergonomic keyboard 10 including a housing 15 on top of which are provided a receptacle 20 for the base part of a person's left hand, and a plurality of keys 31 37. One of keys 31-33 are provided for activation by the person's thumb, key 34 for activation by the person's index finger, key 35 for activation by the person's middle finger, key 36 for activation by the person's ring finger, and key 37 for activation by the person's little finger. The person may choose any one of keys 31-33 for activation by his or her thumb. Multiple keys 31-33 are provided for the thumb to account for differing hand sizes. The FMS illustrated in Figure 3 A evaluates the fingers of the subject's left hand. Figure 3B illustrates an FMS that evaluates the fingers of the subject's right hand. Figure 3B also illustrates how the person's right hand is held down in a substantially fixed position by a wrist strap 38 that is attached to the keyboard 10, so that the finger forces are generated substantially by the muscles for moving the fingers over the entire duration of the test. Figure 3B also illustrates a signal conditioning unit 60 connected to the keyboard 10 by a cable and a power supply unit 65 for the signal conditioning unit 60 connected to an AC outlet (not shown). Each of the keys 31-37 of the apparatus depicted in Figure 3 A is "functionally associated" with a force transducer or "force sensor" and a "switch sensor." As used herein, the term "functionally associated" refers to any means of coupling the action of the keys or buttons (i.e. the force sensing members) to the production of signals that can be detected by the force sensor and the switch sensor. Different types of digital or analog force sensors can be used, such as a FLEXIFORCE™ sensor (Telescan, Inc., South Boston, MA). Figure 4 is a more detailed illustration of a representative one of the keys 31-37, and shows a force sensor 40. The sensor 40 is supported on a key cap 41 through a resin 42. The resin 42 fills a concave space formed on an upper surface of the key cap 41. The finger force is applied by a person's finger 50 and transmitted through a puck 43, which is preferably plastic, to the key cap 41 to actuate the switch sensor, which is sometimes referred to as "cherry switch", 44. The actuation state (i.e. depressed or released) of the cherry switch 44 is transmitted to a data acquisition card 70 (see Figure 5) over a PC board 45. The force sensor and switch sensor signals are transmitted to the data acquisition card 70 over a cable, which is held onto the housing or case 15 using a double-sided tape 46. In one embodiment, an apparatus such as the one depicted in Figure 3 A is used use as a "training device" to help a user develop the stamina to avoid fatigue. Such an apparatus may have keys with adjustable spacing and resistance. When a subject uses the apparatus over an extended period of time as part of a training program, the onset of fatigue maybe observed to occur later and later. By increasing the resistance and decreasing the spacing between the keys during this training program, the beneficial effects of the training program may be further optimized. In another embodiment of the invention, the apparatus is adapted to measure both the characteristics of the force being applied to the keys via the force sensors, and also the location of the keys (i.e. depressed or released) during application of the force via the key switches, or "switch sensors". Whereas the former allows for measurement of changes in force production which is used to generate a "force production profile," the latter allows for measurement of changes in the timing of key depression and release which is used to generate a "force effect profile" (i.e. force production and force effect). Although in one embodiment of the invention both force profiles are generated and analyzed, in an alternative embodiment, only one is recorded and analyzed. In either, a change or "trend" in the profile over time serves as an indicator of the onset of fatigue. In an alternate embodiment of the FMS depicted in Figure 3 A and illustrated in

Figure 4, a force sensor like the one used for the key switches 44 is provided underneath the receptacle 20 for the base part of the hand. As with the force sensors 40 used with the key switches 44, the force sensor for the receptacle measures the force generated by the base of the hand and transmits signals to the signal conditioning unit 60, in particular the analog signal conditioning unit 62, for processing. The forces generated by the base of the hand may be used as another measurement of fatigue, since as the subject becomes fatigued using the fingers, more force will be applied by the base of the hand. Figure 5 is a block diagram of the overall system including the ergonomic keyboard 10, a digital signal conditioning circuit 61 for the keyboard switches, an analog signal conditioning circuit 62 for the force sensors, a data acquisition card 70, a digital signal processing unit 80, and a data display 90. The signal conditioning unit 60 shown in Figure 3B includes both the digital signal conditioning circuit 61 and the analog signal conditioning circuit 62. In the exemplary embodiment, the data acquisition card 70 is installed in a personal computer and the data display 90 constitutes the display unit of the personal computer. Further, the digital signal processing unit 80 comprises a microprocessor for the personal computer executing a series of program steps to store the acquired data in a memory and to retrieve and process the data for graphic representation through the data display 90. As shown in Figure 5, both the keyboard switches and force sensors supply signal to the data acquisition card. In the embodiment as shown, mixed analog and digital signals are transmitted to the data acquisition card (70). However, in an alternate embodiment (not shown), both the keyboard switches and force sensors transmit digital signals to the data acquisition card (70), thereby eliminating the need to amplify the analog signal and convert the amplified analog signal to digital signal for further processing and evaluation. Referring to Figure 6, the digital signal conditioning circuit 61 for the keyboard switches 44 comprises an interface 100 connected to the keyboard switches 44 through a 25- conductor shielded cable 105, and to the data acquisition card 70 through a 68-conductor shielded cable 106. The interface 100 provides, for each keyboard switch 44, an LED 101 connected in series with a pull-up resistor 102 and an inverter 103 between a 5-volt power source and ground. With this arrangement, the LED 101 turns ON when the corresponding keyboard switch 44 is pressed and a HIGH signal is supplied to the data acquisition card 70. The LED 101 provides a visual indication that the digital signal conditioning circuit 61 and the keyboard switches 44 are working properly. Referring to Figure 7, the analog signal conditioning circuit 62 for the flexi- force sensors 40 comprises an interface 110 connected to the sensors 40 through a 25- conductor shielded cable 105 and to the data acquisition card 70 through a 68-conductor shielded cable 106. The interface 110 includes a signal pre-amplifier 111, a filter 112, and an offset calibrator 113. The signal preamplifier 111 and the filter 112 employ a low noise operational amplifier (not shown) in a single-ended arrangement to produce an analog output based on the force applied to the force sensor 40. It also includes a 10-turn potentiometer 114 for signal-gain control to provide a better resolution during the gain-calibration procedures. The output filter 112 includes an operational amplifier, a resistor and a capacitor that are configured to block out high frequency signal components. The cutoff frequency may vary, but can be set to 63 MHz. The offset calibrator 113 includes a 10-turn potentiometer 115 and introduces an offset or bias to the amplified and filtered flexi-force sensor output signal in accordance with the setting of the 10-turn potentiometer 115. Figure 8 is a top view (8 A) and a side view (8B) of a calibrator used for the force sensors. Each key is calibrated separately after the force sensor has been fixed firmly in its place. Various known forces are applied to the force sensor and the electrical output signals are measured. The relationship between the input force magnitude and the output signal magnitude obtained in this manner is used to quantify the applied force in terms of Newtons relative to voltage output. The calibrator illustrated in Figure 8 includes a copper clad board 200, levels 210 secured to the copper clad board 200 with wire straps 220, a copper pipe 230 that extends below the copper clad board 200, and a stainless steel washer 240 mounted on the outer circumference of the copper pipe 230. The operation of the calibrator is as follows. First, using micro-manipulators that encircle the stainless steel washer 240, the copper pipe 230 is placed over the key which has the flex-force sensor. Second, the micro- manipulators that support the calibration platform (mainly the copper clad board 200) are positioned until the levels 210 indicate that the platform is level. Third, weights are placed incrementally on the platform. During this step, the levels, as well as the electronic output, are monitored. Fourth, additional weights are continued to be placed on the platform incrementally until the flexi-force sensor is saturated at a weight that matches the manufacturer's reported force level, e.g., 4 lbs. Fifth, the weights are removed incrementally. Preferably, these steps are repeated two additional times, and throughout this process, the weights placed on the platform and the electrical signal output are recorded. Testing with the FMS is carried out in the following manner. The apparatus is set to sample signals at a given frequency. For example, setting the apparatus to take samples at a frequency of 1000/sec. allows for the accurate capture of EMG signals simultaneously with signals representing force measurements. Lower frequencies can be used when EMG signals are not being measured. The subject is seated in front of the data display 90 referred to in Figure 5, and further depicted in Figure 9, which depicts a sample screen that is displayed to the subject during testing to provide feedback to the subject regarding finger force levels. To begin testing, the subject's hand is placed on the ergonomic keyboard 10 depicted in Figure 4. To determine the target force levels, the subject is first asked to generate the maximum force by way of an isometric contraction of the fingers. The fingers are contracted during this step either all at once or separately. The maximum force levels are used to define the target force level for each finger during the test. The "target force level" is the amount of force the subject is required to produce while striking the keys. This target force level can be defined as thirty percent of the maximum force level, but other percentages may be used as well. The target force levels for each of the fingers are indicated in Figure 9 as "bubbles" 121 -125 in the display. After setting the target force level, the subject is prompted to depress each key repetitively in a particular rhythm established either by the subject or externally for a period of time. The subject can be instructed to depress the keys either individually with the same finger or in sequence by different fingers. The onset of fatigue can be correlated to a drop in finger force level below the target force level. For example, a 20% drop can be defined as the point of fatigue. It is to be understood, however, that the 20% value is only exemplary, and this value may be defined to be larger or smaller. In an alternative embodiment, a metronome may be provided. The metronome aids the subject in depressing the keys according to a predetermined rhythm. The metronome also allows for force measuring of different subjects' under consistent test conditions, and/or force measuring of the same subject at different times under consistent test conditions. After the evaluation session, an exponential curve is fitted to the cumulative data of each peak force value recorded over time, and a drop in amplitude is monitored. Figures 11 A-10E are sample finger force profiles, calibrated in terms of Newtons. Figure 10A is a force production profile for the thumb. Figure 10B is a force production profile for the index finger. Figure 10C is a force production profile for the middle finger. Figure 10D is a force production profile for the ring finger. Figure 10E is a force production profile for the little finger. In each of Figures 10A-10E, the solid line running across the center of the force production profile is the "trend line" (i.e., the exponential curve based on the measurement of amplitude changes). As shown, not all fingers become fatigued at the same rate. In fact, as shown in Figure 10B, after the onset of fatigue (drop in trend line) other muscles are recruited to compensate for the fatigue (raise in trend line). When the drop in amplitude is greater than a predetermined percentage, e.g., 20%, fatigue is considered to have developed. In addition to amplitude changes, each force production profile can also be evaluated for other changes to the force waveform, such as the upward and downward slopes. Furthermore, rather than evaluating the force production profiles separately for each forger, the collective force production profile of all of the fingers may be evaluated in a similar manner. Software packages are commercially available that can be used to analyze various aspects of the force profiles, including the number of key strikes, the time of each key strike depression and release, the width of the force profiles, the amplitude or height of the force production profile, and the area under the force production profile. Analysis of the force effect profile include looking for a trend towards an increase in the time period between depression and release (i.e. the frequency of force effect events which are depicted in Figure 11 as rectangular signal waves). If the repetitive motion is not being timed, such as with a metronome, a decrease in the frequency of the repetitive motion may result in an increase in the time it takes to perform each motion. In addition, when the subject is requested to perform sequential motor movements when timing is closely regulated, such as sequentially depressing keys in time with a metronome, a trend towards an overlap in depression and release from one finger to the next is another indication of fatigue. The software may also record the data submitted by the subject, such as gender, previous complaints, work history, age, and other factors that may affect the person's finger force profile. Graphical representations of the force production profile include force peak, width, and area for all fingers. For example, Figure 1 1 graphically represents the force effect profile generated from the depression and release of the keys (dotted line) along with the force production profile generated from the force waveform (solid line). Figure 12 is an illustration of a FMS which is interfaced with a personal computer system that includes a case 130, a display 131, input devices which may include a keyboard 132, a mouse 133, and a joystick 134. The signal conditioning unit and the data acquisition card of the FMS are housed inside the case 130 and are controlled by the microprocessor of the personal computer system which is also housed inside the case 130. In an alternative embodiment, rather than the force measuring system being directly connected to the computer with which the signal processing and data analysis will occur, the EMS may be adapted to be capable of sending force profile signals via wireless transmission to a computer at a remote location. In one embodiment, one or more of the keys of the keyboard 132 may include a flexi-force sensor which transmits signal proportional to the force applied to the corresponding key to the signal conditioning unit housed in the case 130. Alternatively, one or both of the mouse buttons 150 may include such a flexi-force sensor. An additional sensor may be provided on the mouse to measure the forces generated by the palm of the hand as the user is holding the mouse. The signals from this palm force sensor may be used as another measurement of fatigue, since as the person becomes fatigued using the fingers, he or she will put more force on the palm force sensor. In yet another embodiment, a joystick 134 with afire button 160 and/or afire trigger 161 may be used as the input device. Either or both of the fire button 160 and the fire trigger 161 may include a force sensor. An additional sensor may also be provided on the joystick shaft to measure the forces generated by the palm of the hand as the user is holding the joystick shaft. The signals from this palm force sensor can be used as another measurement of fatigue, since as the person becomes fatigued activating the fire trigger 161, he or she will put more force on the palm force sensor. Figure 13 is an illustration of the FMS shown in Figure 3B, which also includes a plurality of EMG preamps 180 for attachment to the test subject's muscles that generate the finger forces, namely the forearm muscles. The EMG preamps are connected to the signal conditioning unit 60 by a plurality of cables, and the EMG signals that are collected are correlated with the force profiles. The circuit for producing the EMG signals is considered to be well known in the art and is described, for example, in Eskelinen, U.S. Patent No. 5,349,963. However, to correlate force data and EMG signal, it is preferred to measure force at a level of 1 kHz. An increase in the slope of EMG signal amplitude or a decrease in the median frequency of the EMG signal are considered to be objective signs of fatigue, and these objective signs may be correlated with various characteristics of the force profile that are measured using the FMS, including but not limited to: slope, intercept, start and end of the signal, percentage change between the start and end of the signal, the total time of the repetitive motion and the ratio between the percentage change divided by the total time. For example, the EMG data may be superimposed with the force profile and the key depression and release. This allows one to visualize the electrical activity that generates the force that causes the key depression and release simultaneously with the force measurement. The FMS of the present invention can also be incorporated into any mechanical device that interfaces with a computer. There are several specific additional applications that are contemplated. The first is in the area of affective computing. Presently, systems are being developed to monitor, inter alia, heart rate, blood pressure and sweat rate while persons operate a computer to get an indirect reflection of their emotional state. Affective computing assumes that the way a person hits a key may not only reflect physiological forces but also an emotional component. Thus, the amount of force being generated may be influenced by emotional factors. Regardless, the force profile may provide important feedback to the subject (or other person, such as a prospective or current employer) regarding the subject's overall state of wellness, The FMS may also be used in the evaluation of strengthening devices. As carpal tunnel syndrome (CTS) and other forms of RSI increase, it is expected that the market for various forms of finger strengthening devices will increase. The present invention may be used in conjunction with such devices to monitor the characteristics of force produced by a body part while using such a strengthening device. The FMS may also be incorporated into any system in which force is repetitively being produced to give feedback to the subject to decrease the amount of force that they are producing. This feedback would act to minimize RSI caused by the generation of excessive force after the onset of fatigue. The FMS may be also used to evaluate the efficacy of various clinical interventions. Measurements of the force profile before and after clinical treatment for CTS or any other RSI may be an objective measurement of the efficacy of clinical interventions. In addition, the FMS may be used to quantify various motor problems in subjects suffering from various diseases ranging from schizophrenia to Parkinson's disease. In some cases, finger tapping is a clinical assessment of motor problems. In addition, in medical fields such as physical therapy or occupational therapy, mechanical devices are used to evaluate and/or increase the strength or dexterity of the subject. The FMS is not limited to keyboards, joysticks or a mouse but can be used in conjunction with any mechanical system that involves repetitive motor movements such as the fingers twisting a bolt or putting objects into specific locations. In addition, the FMS may be used as an important pre-employment tool. Evaluating a person's force profile as described herein may be used before employment, and would serve as a benchmark in the event that the employee subsequently develops RSI or alleges that they do. Another application for the FMS of the present invention is its use in assisting an individual playing sports to make changes to optimize the outcome of their motor movements. For example, if a FMS is incorporated into a golf club handle, a golfer may be alerted when the club is being held too tight in order to learn when to loosen her grip. It will also be understood that the present invention may be used in situations where monitoring fatigue per se is not necessary. For example, the FMS may be interfaced with a computer-driven game, and the force profiles may be used as input to the game to modify the scenario, the rate of presentation for the player, or any other game parameter. For example, force sensors may be included in buttons of the game controllers, and data from the force sensors can be processed by the computer to evaluate how the person is playing in terms of the characteristics (e.g. speed, amount, decline, etc.) offeree that they apply to certain buttons during the game. The computer can then modify the game in any manner, such as making it more challenging. In addition, EMG data (or other data representative of physical or physiochemical manifestations, such as electrocardiograms, electroencephalograms and/or galvanic skin responses) may be monitored as well, and this activity data may be used by the computer alone or in conjunction with the force data to modify the game. To carry out the above functions, the computer may also be programmed to have some form of software interface such as a neural network configuration or other program that monitors the force profile of the player(s) and modifies the game. Indeed, the FMS when correlated with EMG signals may be used to further evaluate the force produced and the onset of fatigue during any repetitive motions. For example, the FMS can be interfaced with any piece of exercise equipment, such as a bicycle, or any isotonic or isokinetic strengthening system, to provide information about force and fatigue. Other applications include the following: measuring the change in force one generates when standing on a mat as an indication that the person is fatigued and should sit down; measuring the change of force applied by the wrist to a wrist pad or by the forearm to an armchair when typing as an indicator of fatigue; measuring the change of force while using power tools for industrial safety in setting limits on the time period that the tools can be used to prevent fatigue-related accidents; and biometric applications involving use of the force profiles for identifying individuals or classes of individuals with similar profiles. The latter can be used in conjunction with other physiological signatures or biometrics, such as voice recognition, for "fingerprinting" an individual. In addition to the aforementioned applications, the present invention can be adopted to provide "biofeedback" information to the subject by displaying either or both type(s) of force profile(s) on a video monitor, which the subject would then be expected to react to by changing their application of force to the force sensing apparatus. Other Muscle Function Measurements As discussed above, EMGs either alone or in combination with a force measuring system may be employed for monitoring muscle function. Alternatively, pressure sensors, cameras, implantable tendon force transducers, blood pressure monitors, heart rate monitors, etc., may also be used. Diagnostic and Therapeutic Applications The systems and methods of the present invention are useful in a variety of different clinical and research settings. In fact, they are useful for any application in which an understanding of localized muscle physiology is desirable. In clinical settings, the invention is useful from both a diagnostic and a therapeutic perspective. In research settings, the invention is useful to develop a greater understanding of the cause and effect relationship between muscle metabolism and function. Examples of uses of the present invention include, for example, the analysis of localized muscle physiology in diabetic patients, especially the limbs, for evidence of the onset of diabetes-related impairments such as neuropathy. For example, when a diabetes patient complains of numbness, tingling and pain in one of the feet, the present invention is useful for comparing the muscle physiology between the affected foot and the unaffected foot to determine if there is a difference. Other uses of the present invention include detection of repetitive stress injuries such as CTS, as well as monitoring the progression of the condition before, during and/or after treatment. For example, the systems and methods of the present invention are useful to monitor the progression of a disease condition such as RSI during an exercise program designed to alleviate the symptoms of the condition. Such an application can include a determination of which and to what degree particular muscles are "working" (i.e., metabolizing) during an exercise program. In addition, the systems and methods are useful in the design of an exercise program and can be used to determine the "endpoint" of a exercise regime, after which continued exercise may result in exacerbation of clinical symptoms. Alternatively, the systems and methods are useful to evaluate the effectiveness of various intervention techniques such as surgery. For example, surgical intervention in CTS involves the release of pressure on the median nerve in the carpal tunnel. Such intervention has enjoyed mixed success, and the present invention is useful in monitoring the effectiveness of surgery and ongoing treatment during recovery. In one embodiment, LAIRS is used to monitor oxyhemoglobin, deoxyhemoglobin, total hemoglobin and/or hematocrit (i.e. muscle metabolism) in conjunction with monitoring the force, velocity, acceleration and/or displacement of target muscle s ( . e. , muscle function) over time to the point of muscle fatigue. The greater the fall in oxygen levels, the more the muscle is contracting. Alternatively or in conjunction with the aforementioned measurements of muscle function, EMG measurements are taken. The greater the amplitude of the EMG signal, the greater the level of contraction. Using the techniques described above during repetitive movements on a keyboard allows for the clinical prediction of the pathology of persons suffering from RSI such as CTS. Interestingly, CTS sufferers do not show a fall in oxygen levels, which indicates an alteration in peripheral vascular physiology. In addition to the aforementioned uses, the present invention is useful to: ascertain the effectiveness of various strength developing devices; study the effects of repetitive movement of any body part, such as the elbow, knee, foot, torso, etc.; study the effectiveness of ergonomic aids such as splints, wrist supports, etc.

Computer systems and computer program products The invention provides articles (e.g., computer program products) comprising a machine-readable medium including machine-executable instructions, computer systems and computer implemented methods to practice the methods of the invention, e.g., for reading, collating, correlating, displaying and/or storing data produced by apparatus used in the systems and methods of the invention, e.g., for monitoring muscle metabolism function and/or for monitoring muscle function; for diagnosing a muscle disease or dysfunction; for ascertaining the effectiveness of various strength developing devices; to study the effects of repetitive movement of any body part, such as the elbow, knee, foot, torso, etc.; to study the effectiveness of ergonomic aids, and the like. Accordingly, the invention provides computers, computer systems, computer readable mediums, computer programs products and the like having recorded or stored thereon machine-executable instructions to practice the methods of the invention. As used herein, the words "recorded" and "stored" refer to a process for storing information on a computer medium. A skilled artisan can readily adopt any known methods for recording information on a computer to practice the methods of the invention. The methods of the invention can be practiced using any program language or computer / processor and in conjunction with any known software or methodology. Another aspect of the invention is a computer readable medium having recorded thereon machine-executable instructions to practice the methods of the invention. Computer readable media include magnetically readable media, optically readable media, electronically readable media and magnetic/optical media. For example, the computer readable media may be a hard disk, a floppy disk, a magnetic tape, CD-ROM, Digital Versatile Disk (DVD), Random Access Memory (RAM), or Read Only Memory (ROM) as well as other types of other media known to those skilled in the art. The computer/ processor used to practice the methods of the invention can be a conventional general-purpose digital computer, e.g., a personal "workstation" computer, including conventional elements such as microprocessor and data transfer bus. The computer/ processor can further include any form of memory elements, such as dynamic random access memory, flash memory or the like, or mass storage such as magnetic disc optional storage. For example, a conventional personal computer such as those based on an Intel microprocessor and running a Windows operating system can be used. Any hardware or software configuration can be used to practice the methods of the invention. For example, computers based on other well-known microprocessors and running operating system software such as UNIX, Linux, MacOS and others are contemplated. As used herein, the terms "computer," "computer program" and "processor" are used in their broadest general contexts and incorporate all such devices.

The following examples are offered to illustrate but not to limit the invention.

EXAMPLES Example 1 : Studies of CTS Patients and Normal Subjects Using NIRS The following example demonstrates how the systems and methods of the invention are effective in the analysis and measurement of muscle function and metabolism, e.g., to facilitate the diagnosis of a muscle pathology in a subject. Normal individuals and those reported suffering from CTS were studied in two different paradigms: Study 1 : Keyboard Subjects were seated and surface EMGs from the extensors and flexors of the forearm were recorded simultaneous with the measurement of sequential force as the fingers hit the keyboard of the FMS. In addition, a mechanical typewriter to which there were no force transducers attached was also used. In both instances, the subjects were instructed to sequentially hit the keys at a rate of 120 - 180 times a minute until they were fatigued. The NLRS device, Hutchinson Inspectra, was attached to the extensor surface of the forearm and StO₂ levels were recorded during the performance of the repetitive motion to the point of fatigue. Before the experiment, baseline levels of both EMG and StO₂ were recorded while the subjects were at rest. Study 2: Torque device A torque device was used that is adapted to measure torque forces while a subject turns a device member, similar to a doorknob, that generates resistance. The measured torque represents the force produced during rotation of the device member around an axis. Subjects stood and surface EMGs from the extensors of the forearm and biceps were recorded as the subject generated sequential torque to the point of fatigue. The LAIRS device, Hutchinson Inspectra, was attached to the biceps and used to record the StO₂ levels during the performance of the repetitive motion to the point of fatigue. Before the experiment, baseline levels of both EMG and StO₂ were recorded while the subjects were at rest. Results from Study 1 : A. Force measuring keyboard - Normal subjects. Right side. The results of this study are shown in Figure 15. As shown, there is a fall in the hemoglobin-oxygen saturation curve (reported as "StO₂", which is a measure of tissue oxygenation in terms of the dissociation of oxygen from oxygenated hemoglobin, or "HbO₂") with repetitive exercise to the point of fatigue. Trace 5 demonstrates that the initial StO is approximately 90%. As exercise continues, the level of StO₂ falls as a result of the demand on the muscle cells for oxygen. Also as shown in the first and fourth trace, the amplitude of the EMG increases with the fall in StO₂. Thus, the EMG and StO₂ values are inversely proportional in normal subjects and a change in this predictable relationship indicates a pathological condition. The second and third traces measure EMG frequency changes which as shown do not significantly change in normal subjects. Left side. The results of this study are shown in Figure 16. As shown, the non dominant side exhibited a decrease in oxygen levels (trace 5), but this decrease was less pronounced than the dominant side shown in Figure 15. This is because, as the rate offeree production increased, the amount of oxygen used by the muscle increased. The EMG amplitude also increased (trace 1 and 4) as the oxygen levels fell (trace 5). At the end of the experiment, the oxygen levels returned to normal instantaneously (not shown in Figure 16). The interpretation of these results is as follows: as the muscle contracts, it requires oxygen. The more force that is required when the rate of muscle contraction is increased, the greater the fall in oxygen. For the muscle to generate greater EMGs, it requires oxygen. Thus, the greater the fall in oxygen, the greater the amplitude of EMGs. At the end of the experiment, the oxygen values returned to normal (not shown in Figure 16), since the muscles no longer required the energy. B. Force measuring keyboard - CTS patients Right (afflicted) side. The results of this study are shown in Figure 17. This patient complained about pain during any kind of repetitive motion and had pronounced edema in the hand and forearm. As shown, the StO₂ level (trace 5) was initially low (<50%) and , decreased marginally (<10%) over the duration of the exercise. Simultaneously, the EMG signals did not significantly change (traces 1 and 4). Both values are initially low and remain low, indicating that the patient could not generate much force. The recovery to normal oxygen levels was also slow (not shown in Figure 17). Left (non-afflicted) side. The results of this study are shown in Figure 18. The patient claimed that there was no pain associated with use of the left hand. However, as shown, baseline StO₂ levels were initially low and decreased over time (trace 5). Additionally, this person had difficulty doing exercise as shown by the increased EMG amplitude (trace 1 and 4), presumably because of prolonged overuse of the non-afflicted hand/arm in compensating for the afflicted hand/arm. EMG amplitude values were also higher overall than with right side, indicating that using the non-afflicted side, the subject was capable of producing much more force. C. Mechanical keyboard-Nonnal subjects Right side. The dominant side showed a greater decrease in oxygen levels than with the mechanical (force measuring) keyboard. EMGs were larger and the extensor activity was greater. Left side. The non-afflicted side showed a greater decrease in oxygen levels than with the mechanical FMS keyboard, but these values were lower than the right side. D. Mechanical Keyboard-CTS patients Right side - the afflicted side showed almost no decrease in oxygen saturation. EMGs were also smaller. Left side - the non-afflicted side showed a greater drop in oxygen levels than the right side. EMGs were correspondingly larger than the afflicted side. The interpretation of these results is that individuals with CTS are not able to utilize oxygen attached to the hemoglobin as well as normal subjects. As a consequence, they cannot produces the forces necessary to depress the keys of a keyboard for as long a time period as normal individuals, since they are not able to produce the requisite energy. It is likely that, since they are less efficient at aerobic energy production, they are producing large amounts of lactic acid, which causes the burning sensation commonly reported by these patients. In summary, the oxygen is available to the CTS patients, but it is not capable of being utilized by the muscles. This observation suggests that the CTS patients exhibit abnormal muscle metabolism, as well as abnormal muscle function. Such correlative findings are helpful in the diagnosis of CTS patients, as well as in the design and monitoring of treatment protocols. Results from Study 2: A. Normal subjects Right side - the dominant side show a rapid decrease in oxygen levels in the biceps with a corresponding increase in the EMG amplitude. The oxygen levels in the biceps declined to a greater degree than the extensors, which indicates that the biceps were the muscles performing the majority of the "work" in this study. Left side - the non-dominant side showed a rapid decrease in oxygen levels in the biceps with a corresponding increase in the EMG amplitude, but these values were lower than on the dominant side. The same differences in oxygen levels between biceps and extensors were observed on the non-dominant side. B. CTS Patients Right side - the afflicted side did not show as great a decline in oxygen levels as that observed in normal subjects in the biceps. EMG amplitudes were also lower. Left side - the non-afflicted side showed more of a fall in oxygen levels in the biceps and larger EMG amplitude values than on the afflicted side. The interpretation of these results is similar to that described above using the keyboards. CTS patients had difficulty performing the torque-producing tasks, since they had pain in attempting to turn the torque device. The afflicted side exhibited diminished capacity to utilize oxygen, although it was observed that the same level of oxygen was available. The non- afflicted side exhibited more oxygen depletion than the afflicted side and consequently was able to generate more force.

Numerous modifications may be made to the foregoing invention without departing from the basic teachings thereof. Although the present invention has been described in substantial detail with reference to one or more specific embodiments, those of skill in the art will recognize that changes may be made to the embodiments specifically disclosed in this application, yet these modifications and improvements are within the scope and spirit of the invention as set forth in the claims which follow. All publications, patents, and patent applications cited in this specification are incorporated herein by reference as if each such publication, patent, or patent application was specifically and individually indicated to be incorporated herein by reference.

Claims

WHAT IS CLAIMED IS: 1. A system for analyzing or studying muscle physiology comprising: an apparatus for monitoring muscle metabolism over time; and, an apparatus for monitoring muscle function over time.

2. A system for analyzing or studying muscle physiology comprising: means for monitoring muscle metabolism over time; and, means for monitoring muscle function over time.

3. The system according to claim 1 or claim 2, wherein the apparatus or means for monitoring muscle metabolism is selected from the group consisting of: a skin sensor for measuring skin-secreted muscle-related analyte concentration; an apparatus for measuring blood or skin pH; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration in a bodily fluid; a near infrared spectroscopy system for measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, hematocrit, tissue water content; an apparatus for measuring skin or body temperature; and, a combination thereof.

4. The system according to claim 1 or claim 2 wherein the apparatus or means for monitoring muscle function is selected from the group consisting of: a force measuring system for measuring a force profile; an acceleration measuring system for measuring acceleration of system members in a plane upon which force is applied; a blood pressure monitor; a heart rate monitor; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration; an electromyelogram device; and a combination thereof.

5. The system according to claim 1 or claim 2, further comprising an apparatus or device for correlating data produced by the apparatus or means for monitoring muscle metabolism function and the apparatus or means for monitoring the muscle function.

6. The system according to claim 1 or claim 2, further comprising an apparatus or means for correlating data produced by the apparatus or means for monitoring muscle metabolism function.

7. The system of claim 6, wherein the data is correlated using a computer- run program.

8. The system according to claim 1 or claim 2, wherein the muscle function monitoring comprises monitoring isotonic muscle movements.

9. The system according to claim 1 or claim 2, wherein the muscle function monitoring comprises monitoring of a single muscle or a set of muscles.

10. The system of claim 9, wherein the muscle function monitoring comprises simultaneously monitoring all the muscles in a hand, a leg, or an arm.

11. The system according to claim 1 or claim 2, further comprising an ergonomic keyboard for generating finger force profiles.

12. A method for analyzing or studying muscle physiology comprising: monitoring muscle metabolism over time; and, monitoring muscle function over time.

13. The method of claim 12, wherein the muscle metabolism is monitored by a skin sensor for measuring skin-secreted muscle-related analyte concentration; an apparatus for measuring blood or skin pH; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration in a bodily fluid; a near infrared spectroscopy system for measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, hematocrit, tissue water content; an apparatus for measuring skin or body temperature; or, a combination thereof.

14. The method of claim 12, wherein the muscle function is monitored by a force measuring system for measuring a force profile; an acceleration measuring system for measuring acceleration of system members in a plane upon which force is applied; a blood pressure monitor; a heart rate monitor; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration; an electromyelogram device; or, a combination thereof.

15. The method of claim 12, comprising use of an ergonomic keyboard for generating finger force profiles.

16. The method of claim 12, wherein the muscle metabolism over time and the muscle function over time are simultaneously monitored, or, muscle function is measured at one time and muscle metabolism is measured at another time under the same or similar conditions.

17. The method of claim 12, wherein the muscle function monitoring comprises monitoring isotonic muscle movements.

18. The method of claim 12, wherein the muscle function monitoring comprises monitoring of a single muscle or a set of muscles.

19. The method of claim 12, wherein the muscle function monitoring comprises simultaneously monitoring all the muscles in a hand, a leg, or an arm.

20. The method of claim 12, further comprising correlating the muscle metabolism over time data and the metabolism function over time data.

21. The method of claim 20, wherein the data is correlated using a computer-run program.

22. A method for measuring muscle fatigue of a subject comprising: (a) instructing the subject to apply repetitive force to an apparatus, wherein the apparatus has an accelerometer functionally attached thereto for generating an acceleration profile; and (b) monitoring the acceleration profile over time during application of the repetitive force.

23. A method for measuring changes in reflected or attenuated spectral features of whole blood in tissues before, during and/or after performance of repetitive tasks in a subject comprising: (a) instructing the subject to apply repetitive force to an apparatus, wherein the apparatus has an accelerometer functionally attached thereto for generating an acceleration profile; and (b) monitoring the reflected or attenuated spectral features in the whole blood in the tissues of the subject before, during and/or after performance of the repetitive tasks.

24. A method for diagnosing or assessing carpal tunnel syndrome (CTS) in an individual, comprising the steps of: monitoring muscle metabolism over time; monitoring muscle function over time; and, monitoring pain, wherein CTS patients exhibit a decrease in muscle function associated with the onset of pain localized in the hand, forearm, elbow or shoulder.

25. The method of claim 24, wherein the muscle metabolism is monitored by a skin sensor for measuring skin-secreted muscle-related analyte concentration; an apparatus for measuring blood or skin pH; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration in a bodily fluid; a near infrared spectroscopy system for measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, hematocrit, tissue water content; an apparatus for measuring skin or body temperature; or, a combination thereof.

26. The method of claim 24, wherein the muscle function is monitored by a force measuring system for measuring a force profile; an acceleration measuring system for measuring acceleration of system members in a plane upon which force is applied; a blood pressure monitor; a heart rate monitor; a blood analyte analyzer capable of measuring a muscle-related blood analyte concentration; an electromyelogram device; or, a combination thereof.

27. The method of claim 24, wherein the muscle metabolism over time and the muscle function over time are simultaneously monitored during isotonic muscle movements.

28. The method of claim 24, further comprising correlating the muscle metabolism over time data and the metabolism function over time data.

29. A method for facilitating diagnosis of a muscle pathology in a subject comprising the steps of monitoring metabolism of a muscle or a group of muscles over a set period of time, monitoring function of these muscles over the set period of time, determining a correlation between the metabolism and the function of the muscle or a group of muscles, wherein if the relationship between the metabolism and the function is not within a normal range for the same muscle or a group of muscles a diagnosis of a particular pathology can be facilitated.

30. The method of clam 29, wherein the facilitated diagnosis comprises analysis of localized muscle physiology in a diabetic patient.

31. The method of any of the claims 12 to 30, wherein the method comprises monitoring muscle metabolism function and/or for monitoring muscle function; diagnosing a muscle disease or dysfunction; ascertaining the effectiveness of various strength developing devices; studying the effects of repetitive movement of a body part; or studying the effectiveness of ergonomic aids.

32. A computer program product comprising a machine-readable medium comprising machine-executable instructions, computer systems and/or computer implemented methods for reading, collating, correlating, displaying and/or storing data produced by an apparatus as set forth any one of claims 1 to 11, or, a method as set forth in any of claims to 12 to 30.

33. The computer program product of claim 32, wherein the method comprises monitoring muscle metabolism function and/or for monitoring muscle function; diagnosing a muscle disease or dysfunction; ascertaining the effectiveness of various strength developing devices; studying the effects of repetitive movement of a body part; or studying the effectiveness of ergonomic aids.