CROSS-REFERNECE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to (i) U.S. Provisional Application No. 63/324,363 entitled “Methods and Systems for Diagnosing and Treating Fibromyalgia,” filed on March 28, 2022, and (ii) U.S. Provisional Application No. 63/324,376 entitled “Methods and Systems for Diagnosing and Treating Fibromyalgia,” filed on March 28, 2022, the contents of each of which are hereby incorporated by reference in their entirety.

TECHNICAL FIELD

[0002] The present disclosure provides methods and systems for diagnosing and treating fibromyalgia in a patient.

BACKGROUND

[0003] Unless otherwise indicated herein, the materials described in this section are not admitted to be prior art to the claims in this application.

[0004] Fibromyalgia is chronic widespread pam associated with insomnia, fatigue, and cognitive dysfunction. Surveys in the United States estimate that fibromyalgia affects approximately 2-8% of the adult population. Although there currently is no objective test for determining whether a patient suffers from fibromyalgia, a diagnosis of fibromyalgia has become much more credible since the American College of Rheumatology (ACR) defined the illness in 1990 using agreed-upon criteria. Nevertheless, approximately 25% of fibromyalgia patients still do not satisfy the ACR 1990 classification criteria (Wolfe et al., Arthritis Care Res. 62(5): 600-10 (2010)). Indeed, fibromyalgia may be associated with a significant percentage of the 10-12% of the U.S. population that suffers from chronic pain. In 2010, fibromyalgia criteria were changed, primarily because the requirement of having eleven tender points over a possible eighteen throughout the body was difficult to apply in practice. Also, these tender points vary from time to time and could not be relied on for a diagnosis of fibromyalgia, but the other criteria of widespread pain (up to nineteen areas throughout the body), poor sleep, fatigue, and cognitive symptoms, especially memory loss and concentration problems, were maintained as essential criteria for the diagnosis. [0005] Although there are guidelines for the diagnosis of fibromyalgia, and clinicians generally agree about such a diagnosis, there remains no specific, reliable test for fibromyalgia. Currently, there is no single test that can fully diagnose fibromyalgia, and there is some debate over the symptoms that should be considered as essential diagnostic criteria and whether an objective diagnosis may be possible. Existing methods of diagnosing fibromyalgia typically use subjective pain values provided by the patient for several areas of the body. As such, one patient's score on such a test is difficult to compare with another patient's score since pain thresholds may vary from patient to patient. Therefore, an improved objective method for diagnosing fibromyalgia and evaluating treatment of patients with fibromyalgia is desired.

SUMMARY

[0006] In view of the foregoing, the present disclosure provides methods and systems for diagnosing fibromyalgia in a patient by measuring muscle oxygenation.

[0007] In a first aspect, the present disclosure provides method for diagnosing fibromyalgia in a patient comprising: (a) obtaining an oxygenation level at a muscle location in the patient; and (b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0008] In a second aspect, the present disclosure provides a method for treating fibromyalgia in a patient comprising: (a) obtaining an oxygenation level at a muscle location in the patient; and (b) administering an effective amount of a muscle relaxant to the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0009] In a third aspect, the present disclosure provides a method of detecting an oxygenation level at a muscle location in a patient suspected of having fibromyalgia comprising: (a) obtaining the oxygenation level at the muscle location in the patient; and (b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0010] In a fourth aspect, the present disclosure provides a method for diagnosing and treating fibromyalgia in a patient comprising: (a) obtaining an oxygenation level at a muscle location in the patient; (b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level; and (c) administering an effective amount of a muscle relaxant to the diagnosed patient if the oxygenation level at the muscle location is lower than the threshold oxygenation level. [0011] In a fifth aspect, the present disclosure provides method for diagnosing fibromyalgia in a patient comprising: (a) obtaining a muscle firmness at a muscle location in the patient; and (b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0012] In a sixth aspect, the present disclosure provides a method for treating fibromyalgia in a patient comprising: (a) obtaining a muscle firmness at a muscle location in the patient; and (b) administering an effective amount of a muscle relaxant to the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0013] In a seventh aspect, the present disclosure provides a method of detecting a muscle firmness at a muscle location in a patient suspected of having fibromyalgia comprising: (a) obtaining the muscle firmness at the muscle location in the patient; and (b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0014] In an eighth aspect, the present disclosure provides a method for diagnosing and treating fibromyalgia in a patient comprising: (a) obtaining a muscle firmness at a muscle location in the patient; (b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness; and (c) administering an effective amount of a muscle relaxant to the diagnosed patient if the muscle firmness at the muscle location exceeds the threshold muscle firmness.

[0015] These as well as other aspects, advantages, and alternatives, will become apparent to those of ordinary skill in the art by reading the following detailed description, with reference where appropriate to the accompanying drawings.

DETAILED DESCRIPTION

[0016] Exemplary methods and systems are described herein. It should be understood that the words "example," "exemplary," and "illustrative" are used herein to mean "serving as an example, instance, or illustration." Any embodiment or feature described herein as being an "example," "exemplary," and "illustrative" is not necessarily to be construed as preferred or advantageous over other embodiments or features. The exemplary embodiments described herein are not meant to be limiting. It will be readily understood that the aspects of the present disclosure, as generally described herein and illustrated in the figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein. [0017] Furthermore, the particular arrangements shown in the Figures should not be viewed as limiting. It should be understood that other embodiments may include more or less of each element shown in a given Figure. Further, some of the illustrated elements may be combined or omitted. Yet further, an exemplary embodiment may include elements that are not illustrated in the Figures.

[0018] As used herein, with respect to measurements, "about" means +/- 5%.

[0019] The term "patient" as used herein refers to a human subject.

[0020] A "disease" or "disorder" is any condition that would benefit from treatment using the methods or compositions of the invention. "Disease," "disorder," and "condition" are used interchangeably herein and include chronic and acute disorders or diseases.

[0021] The term "treat" as used herein refers to both therapeutic treatment and prophylactic or preventative measures. The term "treatment" as used herein refers to the alleviation of symptoms of a disease. Those in need of treatment include those having the disorder as well as those prone to have the disorder or those in which the disorder is to be prevented.

[0022] The terms "composition," "therapeutic composition," or "pharmaceutical composition" as used herein refer to a compound or composition capable of inducing a desired therapeutic effect when properly administered to a patient.

[0023] The term "therapeutically acceptable" as used herein refers to one or more formulation materials suitable for accomplishing or enhancing the delivery of a composition of the invention.

[0024] The term "functional improvement" as used herein refers to a partial and/or complete, but in any case, significant improvement or restoration of at least one aspect of normal function to a state observed before onset of fibromyalgia symptoms. This is determined for each patient, e.g., by comparing the functional improvement following drug treatment with reference to the functional efficiency in a healthy population or before onset of fibromyalgia symptoms. Typically, the determination of improvement in one or more features of fibromyalgia recognized by the American College of Rheumatology (ACR) criteria for diagnosis (e.g., dyscognition, fatigue, pain, energy, mood, muscle pain, irritable bowel syndrome, thinking or remembering problems, muscle weakness, headache, numbness/tingling, dizziness, insomnia, and depression) will be indicative of overall functional improvement. Most tests combine one or more of these aspects of features of fibromyalgia. Functional restoration or improvement of features of fibromyalgia can for instance be evaluated and/or quantified using the Health Assessment Questionnaire (HAQ), which is a short measurement questionnaire regarding patient function. HAQ scores are calculated based on a patient checking a short form about the activities of daily living that the patient is able to do. Additionally, the degree of functional improvement or restoration is measured using a Widespread Pain Index or Symptom Severity scale score. Additionally or alternatively, the degree of functional improvement or restoration can be measured using the methods as disclosed herein (e.g., determining that the oxy genation level at the muscle location of a patient has decreased or is below a threshold oxygenation level following treatment). Functional improvement can prevent disability as many fibromyalgia patients conclude that they can no longer work due to fatigue, cognitive problems, and pain.

[0025] The terms "pain scale" and "pain score" as used herein refer to one or more scaling or scoring systems typically used to rate a pain level in a patient. Typically, the pain scaling or pain scoring schemes rank pain from 0-10 (0 = no pain, and 10 = worst pain imaginable). For example, a score of zero would be no pain, a score from 1-3 would be mild pain (e.g., nagging, annoying, interfering little with daily life activities), a score between 4-6 would be moderate pain (e.g., interferes significantly with daily life activities), and a score between 7-10 would be severe pain (e.g, disabling; unable to perform daily life activities).

[0026] The terms "dolorimetry score" or "dolorimetry reading" as used herein refer to one or more ranking schemes used to measure a pain sensitivity or pain intensity in a patient. Dolorimetry can be measured by known methods readily available to those of skill in the art. For example, dolorimeter devices can apply steady pressure, heat, or electrical stimulation to some area, or move a joint or other body part and determine what level of heat or pressure or electric current or amount of movement produces a sensation of pain. Sometimes the pressure can be applied using a blunt object, or by locally increasing the air pressure on some area of the body, and sometimes by pressing a sharp instrument against the body. For example, if a dolorimeter device applies a steady pressure that gradually increases between, for example, 0 and 30 pounds, then as the dolorimeter device gradually increases the steady pressure on a body part, the point at which a patient indicates a sensation of pain is the dolorimetry score or dolorimetry reading (e.g. a sensation of pain at 8 pounds, is a score of 8).

[0027] The terms "muscle tenderness" or "tenderness" as used herein refer to one or more ranking schemes used to measure a pain sensitivity in a muscle of a patient. Tenderness can be scored by known methods readily available to those of skill in the art. For example, muscle tenderness can be scored on a scale of 0 to 3, wherein 0 is no tenderness, 1 is mild tenderness, 2 is moderate tenderness and 3 is severe tenderness. As such, one or more of a plurality of muscle tenderness categories could be mild muscle tenderness, moderate muscle tenderness, and severe muscle tenderness. Other categories of tenderness are possible as well. [0028] Currently, there is no single test that can fully diagnose fibromyalgia, and there is debate over the symptoms that should be considered as essential diagnostic criteria and whether an objective diagnosis may be possible. Existing methods of diagnosing fibromyalgia typically use subjective pain values provided by the patient for several areas of the body. As such, one patient's score on such a test is difficult to compare with another patient's score since pain thresholds may vary from patient to patient. Therefore, an improved objective method for diagnosing fibromyalgia and evaluating treatment of patients with fibromyalgia is desired.

[0029] The inventors have determined methods for diagnosing fibromyalgia in a patient by at least measuring oxygenation level at a muscle location in a patient.

[0030] In one aspect, the present disclosure provides a method for diagnosing fibromyalgia in a patient comprising: (a) obtaining an oxygenation level at a muscle location in the patient; and (b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0031] In another aspect, the present disclosure provides a method for treating fibromyalgia in a patient comprising: (a) obtaining an oxygenation level at a muscle location in the patient; and (b) administering an effective amount of a muscle relaxant to the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0032] In another aspect, the present disclosure provides a method of detecting an oxygenation level at a muscle location in a patient suspected of having fibromyalgia comprising: (a) obtaining the oxygenation level at the muscle location in the patient; and (b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0033] In another aspect, the present disclosure provides a method for diagnosing and treating fibromyalgia in a patient comprising: (a) obtaining an oxygenation level at a muscle location in the patient; (b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level; and (c) administering an effective amount of a muscle relaxant to the diagnosed patient if the oxygenation level at the muscle location is lower than the threshold oxygenation level.

[0034] In one example, obtaining the oxygenation level at the muscle location in the patient comprises using a near-infrared spectroscopy (NIRS) device. In one example, the NIRS device is wearable on the patient NIRS is an imaging technique that utilizes light (in the spectral range of 700-1000 nm). NIRS is based on other spectroscopy methods that use light and its interaction with materials to scan for specific properties and molecular components. While NIRS has many use cases in multiple industries, in the medical field it is a non-invasive technique that detects the oxygenation state of living tissue roughly 3 cm below the skin. Attenuation of light occurs in different mediums and includes behaviors like photons scattering, absorption, and reflection; the ones dependent on wavelength are absorption and scattering. NIRS measures the absorption coefficient and the scattering coefficient, at different wavelengths, which are analyzed to determine the concentration of oxyhemoglobin (HbO2) and deoxygenated hemoglobin (HHb). It should be noted that myoglobin, a hemoglobin analog found in striated muscle tissue, has similar absorption and scattering profiles to hemoglobin and thus cannot be separated from hemoglobin measurements. Some devices will also show the sum of HbO2 and HHb as changes of total hemoglobin (THb). Regional oxygen saturation (rS02) or tissue oxygenation index (TOI) can be claimed to be measured but it is the ratio of HbO2/THb. The absorption is measured at different wavelengths because different absorbers, like HbO2 and HHb, will absorb radiation at specific wavelengths. The scattering coefficient is measured to determine the distance between the source and detector, as the direction of photons inside a medium can change, and by accommodating for scattering more accurate measurements can be extrapolated. There are three different modalities of NIRS that dictate how the two coefficients are distinguished and determine what kind of technology' is used: Continuous Wave (CW), Time Domain (TD), and Frequency Domain.

[0035] NIRS, when used to measure skeletal oxygenation levels, uses an array of light detectors to measure the light emitted from a separately placed emitter (laser or LED). By placing the light emitter and detectors near the skin of the patient and covering the area with material to block ambient light, the light detectors should then only be measuring the light sent from the emitters after the light has passed through the skin and underlying tissue. Only after receiving information on the amount of light the detectors received and comparing to the predicted amount of light the emitters should emit, do we calculate the estimated scattering and absorption of the sent light through the tissue. By using previous research and applying multiple mathematical models, the absorption values are related to the oxygenation levels within the tissue, ft is within these models do the vast number of recent improvements to the accuracy and reliability of NIRS are made. By modulating the wavelengths of light sent, the frequency and pulse duration of the light, and the position of the detectors, further improvements are made alongside advanced modeling of the light/tissue interaction.

[0036] A final consideration of using NIRS is the importance that many NIRS measurements require an active component. A passive measurement requires no direct action from the subject being measured, a simple example being a heart rate measurement. An active measurement, on the other hand, requires the subject to perform a set task such as lifting a weight or performing a specific exercise. The importance of taking an active measurement highlights a key aspect in using NIRS as using a relative measurement system, such as CW NIRS, it can be hard to draw conclusions across different populations; however, by using an active measurement protocol, the process of comparing two populations becomes clearer as the ability of a muscle to recover from stress can be more directly compared. Thus, the step of obtaining the oxygenation level at the muscle location in the patient may include instructing the patient to perform a set task to ensure an active measurement of the NIRS device.

[0037] In one example, the muscle location in the patient is a trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle. In one particular example, the muscle location in the patient is a trapezius muscle.

[0038] In one example, the muscle location in the patient comprises a first location, and the method further comprises: (a) obtaining an oxygenation level for the patient from a second muscle location; (b) determining an average an oxygenation level based on the an oxygenation level measured at the first muscle location and the an oxygenation level measured at the second muscle location; and (c) diagnosing fibromyalgia in the patient if the average an oxygenation level from the two muscle locations is lower than a threshold an oxygenation level.

[0039] In another example, the method can further include using the measured oxygenation level at the muscle location to associate the patient with one of a plurality of muscle tenderness categories. One or more of the plurality of muscle tenderness categories could be mild muscle tenderness, moderate muscle tenderness, and severe or extreme muscle tenderness. Other categories are possible as well. A treating physician may then use the category information to determine a proper treatment plan for the patient. For example, a patient may receive a higher dosage of a medication if he or she falls into the extreme muscle tenderness category. [0040] In one example, the oxygenation level comprises a first oxygenation level, and the method further comprises: (a) providing a medication to the patient; (b) obtaining a second oxygenation level from the patient from a second muscle location; and (c) comparing the first oxygenation level to the second oxygenation level to determine whether the oxygenation level at the second muscle location has been reduced. In an embodiment, the medication can be a muscle relaxant, although other medications are possible as well. In one embodiment, the method further comprises, in response to a determination that the second oxygenation level at the second muscle location no longer is lower than the threshold oxygenation level, decreasing a dosage of the medication provided to the patient. In another embodiment, the method further comprises, in response to a determination that the second oxygenation level at the second muscle location still is lower than the threshold oxygenation level, increasing a dosage of the medication provided to the patient. In another embodiment, the method further comprises, in response to a determination that the second oxygenation level at the second muscle location still is lower than the threshold oxygenation level, maintaining a dosage of the medication provided to the patient.

[0041] In some embodiments, as discussed above, the methods can include treating a patient with a muscle relaxant. In an embodiment, the method for treating fibromyalgia can result in the amelioration of muscle pressure or muscle tension, muscle fatigue, or pain associated with fibromyalgia. The methods can comprise administering to the patient a therapeutically effective amount of a muscle relaxant. Muscle relaxants are known in the art and can include, but are not limited to, baclofen, carisoprodol (SOMA®), chlorzoxazone (PARAFON FORTE DSC®), cyclobenzapnne (FLEXERIL®, FEXMID®, AMRIX®), dantrolene (DANTRIUM®), metaxalone (SKELAXIN®), methocarbamol (ROBAXIN®), orphenadrine (NORFLEX®) or tizanidine (ZANAFLEX®). In another embodiment, the muscle relaxant is administered in a tablet dosage form. The tablet dosage form can comprise an amount of a muscle relaxant, or a pharmaceutically acceptable equivalent thereof, that can be 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 600 mg, 700 mg, 750 mg, 800 mg, 900 mg, or 1000 mg. In some embodiments, the muscle relaxant is administered in a tablet dosage form one to four times daily, and can be administered at least once a day for at least four weeks. In other embodiments, the muscle relaxant can be in the form of a modified release formulation. [0042] In other embodiments, the methods can include treating a patient with an antidepressant. In an embodiment, the method for treating fibromyalgia can result in the amelioration of muscle pressure or muscle tension, muscle fatigue, pain or other symptoms associated with fibromyalgia. The methods can comprise administering to the patient a therapeutically effective amount of an antidepressant. Antidepressants are known in the art and can include, but are not limited to, ABILITY® (ariprazole), ADAPIN® (doxepin), ANAFRANIL® (clomipramine), APLENZIN® (bupropion), ASENDIN® (amoxapine), AVENTYL HCI® (nortriptyline), BRINTELLIX® (vortioxetine), CELEXA® (citalopram), CYMBALTA® (duloxetine), DESYREL® (trazodone), EFFEXOR XR® (venlafaxine), EMSAM® (selegiline), ETRAFON® (perphenazine and amitriptyline), ELAVIL® (amitriptyline), ENDEP® (amitriptyline), FETZIMA® (levomilnacipran), KHEDEZLA® (desvenlafaxine), LATUDA® (lurasidone), LAMICTAL® (lamotrigine), LEXAPRO® (escitalopram), LIMBITROL® (amitriptyline and chlordiazepoxide), MARPLAN ® (isocarboxazid), NARDIL® (phenelzine), NORPRAMIN® (desipramine), OLEPTRO® (trazodone), PAMELOR® (nortriptyline), PARNATE® (tranylcypromine), PAXIL® (paroxetine), PEXEVA® (paroxetine), PROZAC® (fluoxetine), PRISTIQ® (desvenlafaxine), REMERON® (mirtazapine), SARAFEM® (fluoxetine), SEROQUEL XR® (quetiapine), SERZONE® (nefazodone), SINEQUAN® (doxepin), SURMONTIL® (trimipramine), SYMBYAX® (fluoxetine and the atypical antipsychotic drug olanzapine), TOFRANIL® (imipramine), TRIAVIL® (perphenazine and amitriptyline), VIIBRYD® (vilazodone), VIVACTIL® (protriptyline), WELLBUTRIN® (bupropion), ZOLOFT® (sertraline), or ZYPREXA® (olanzapine). In another embodiment, the antidepressant can be administered in a tablet dosage form. The tablet dosage form can comprise an amount of a antidepressant, or a pharmaceutically acceptable equivalent thereof, that can be 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 600 mg, 700 mg, 750 mg, 800 mg, 900 mg, or 1000 mg. In some embodiments, the antidepressant is administered in a tablet dosage form one to four times daily, and can be administered at least once a day for at least four weeks. In other embodiments, the antidepressant can be in the form of a modified release formulation.

[0043] In another example, the inventors have determined methods for diagnosing fibromyalgia in a patient by at least measuring muscle firmness at a muscle location in a patient. [0044] In one aspect, the present disclosure provides a method for diagnosing fibromyalgia in a patient comprising: (a) obtaining a muscle firmness at a muscle location in the patient; and (b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0045] In another aspect, the present disclosure provides a method for treating fibromyalgia in a patient comprising: (a) obtaining a muscle firmness at a muscle location in the patient; and (b) administering an effective amount of a muscle relaxant to the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0046] In another aspect, the present disclosure provides a method of detecting a muscle firmness at a muscle location in a patient suspected of having fibromyalgia comprising: (a) obtaining the muscle firmness at the muscle location in the patient; and (b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0047] In another aspect, the present disclosure provides a method for diagnosing and treating fibromyalgia in a patient comprising: (a) obtaining a muscle firmness at a muscle location in the patient; (b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness; and (c) administering an effective amount of a muscle relaxant to the diagnosed patient if the muscle firmness at the muscle location exceeds the threshold muscle firmness.

[0048] In one example, obtaining the muscle firmness at the muscle location in the patient comprises using elastography. In one example, an elastography device capable of measuring muscle firmness is wearable by the patient. Elastography is a non-invasive imaging modality that is able to map elastic properties and stiffness of soft tissue. There are many forms of elastography including quasistatic, transient, and shear-wave. The most promising form of elastography to detect muscle stiffness is shear-wave elastography (SWE).

[0049] SWE is a newer and developing form of elastography, but it is increasingly clear that it is capable of measuring musculoskeletal tissue mechanical properties. Not all ultrasound machines are capable of this technology, however it is a newer application that is gaining popularity. SWE works by using a high intensity pulse to produce shear waves that travel faster through stiffer tissue than soft tissue. The shear waves can be tracked with low intensity pulses to receive shear velocity which can be used to calculate stiffness via Young’s modulus.

[0050] SWE is an extension of current ultrasound imaging. Ultrasound is the process of using an array of sound transducers (electronic component capable of converting electrical signals into sound and vice versa) to send above 20 kHz sound waves into the tissue of a subject and then measuring the sound that is reflected to the array of transducers. By understanding the mechanical properties of various tissue types within the human body and accurately measuring the time and amplitude as well as frequency of the sound reflected in comparison to the original sound emitted, one can determine various spatial and mechanical properties of the tissue below the sensor. Typically, a b-mode image is returned to the operator which acts as a 2D image of the tissue though other reporting methods can be used. Shear wave elastography expands upon the standard ultrasound by sending first a targeted acoustic force to generate a shear wave that propagate perpendicular to the standard ultrasound wave. Immediately following the generation of the shear wave, standard ultrasound waves are sent into the tissue to track the speed and direction of the shear wave across multiple b-mode images. By comparing the various parameters, using physical models, and previous research on mechanical properties of the target tissue, the shear modulus can be calculated across the tissue. A secondary image can be overlay ed the initial b-mode image that represents a heat map of shear modulus values across the tissue. With information of the shear modulus, other mechanical properties of the tissue can be estimated such as Young’s modulus, stiffness values, etc.

[0051] One-shot and continuous are the two different methods of SWE. The one-shot method activates the main pulse over one frame to measure the resultant speed of the shear wave and elasticity' in the tissue being examined. A single image is produced to register the stiffness measurements. The continuous mode provides a live acquisition of the elastographic and propagation maps, and multiple images are acquired over time. It is also possible to cine- loop back through the frames to register multiple stiffness measurements from the one acquisition The main benefit to SWE is that it can give a quantitative readout that can be used to determine disease states like fibromyalgia via experimentation.

[0052] In one example, the muscle location in the patient is a trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle. In one particular example, the muscle location in the patient is a trapezius muscle.

[0053] In one example, the muscle location in the patient comprises a first location, and the method further comprises: (a) obtaining a muscle firmness for the patient from a second muscle location; (b) determining an average muscle firmness based on the a muscle firmness measured at the first muscle location and the a muscle firmness measured at the second muscle location; and (c) diagnosing fibromyalgia in the patient if the average a muscle firmness from the two muscle locations exceeds a threshold a muscle firmness.

[0054] In another example, the method can further include using the measured a muscle firmness at the muscle location to associate the patient with one of a plurality of muscle tenderness categories. One or more of the plurality of muscle tenderness categories could be mild muscle tenderness, moderate muscle tenderness, and severe or extreme muscle tenderness. Other categories are possible as well. A treating physician may then use the category information to determine a proper treatment plan for the patient. For example, a patient may receive a higher dosage of a medication if he or she falls into the extreme muscle tenderness category.

[0055] In one example, the muscle firmness comprises a first muscle firmness, and the method further comprises: (a) providing a medication to the patient; (b) obtaining a second muscle firmness from the patient from a second muscle location; and (c) comparing the first muscle firmness to the second muscle firmness to determine whether the muscle firmness at the second muscle location has been reduced. In an embodiment, the medication can be a muscle relaxant, although other medications are possible as well. In one embodiment, the method further comprises, in response to a determination that the second muscle firmness at the second muscle location no longer exceeds the threshold muscle firmness, decreasing a dosage of the medication provided to the patient. In another embodiment, the method further comprises, in response to a determination that the second muscle firmness at the second muscle location still exceeds the threshold muscle firmness, increasing a dosage of the medication provided to the patient. In another embodiment, the method further comprises, in response to a determination that the second muscle firmness at the second muscle location still exceeds the threshold muscle firmness, maintaining a dosage of the medication provided to the patient.

[0056] In some embodiments, as discussed above, the methods can include treating a patient with a muscle relaxant. In an embodiment, the method for treating fibromyalgia can result in the amelioration of muscle pressure or muscle tension, muscle fatigue, or pain associated with fibromyalgia. The methods can comprise administering to the patient a therapeutically effective amount of a muscle relaxant. Muscle relaxants are known in the art and can include, but are not limited to, baclofen, carisoprodol (SOMA®), chlorzoxazone (PARAFON FORTE DSC®), cyclobenzapnne (FLEXER1L®, FEXM1D®, AMRIX®), dantrolene (DANTRIUM®), metaxalone (SKELAXIN®), methocarbamol (ROBAXIN®), orphenadrine (NORFLEX®) or tizanidine (ZANAFLEX®). In another embodiment, the muscle relaxant is administered in a tablet dosage form. The tablet dosage form can comprise an amount of a muscle relaxant, or a pharmaceutically acceptable equivalent thereof, that can be 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 600 mg, 700 mg, 750 mg, 800 mg, 900 mg, or 1000 mg. In some embodiments, the muscle relaxant is administered in a tablet dosage form one to four times daily, and can be administered at least once a day for at least four weeks. In other embodiments, the muscle relaxant can be in the form of a modified release formulation.

[0057] In other embodiments, as discussed above, the methods can include treating a patient with an anti-depressant. In an embodiment, the method for treating fibromyalgia can result in the amelioration of muscle pressure or muscle tension, muscle fatigue, pain or other symptoms associated with fibromyalgia. The methods can comprise administering to the patient a therapeutically effective amount of an antidepressant. Antidepressants are known in the art and can include, but are not limited to, ABILITY® (ariprazole), ADAPIN® (doxepin), ANAFRANIL® (clomipramine), APLENZIN® (bupropion), ASENDIN® (amoxapine), AVENTYL HCI® (nortriptyline), BRINTELLIX® (vortioxetine), CELEXA® (citalopram), CYMBALTA® (duloxetine), DESYREL® (trazodone), EFFEXOR XR® (venlafaxine), EMSAM® (selegiline), ETRAFON® (perphenazine and amitriptyline), ELAVIL® (amitriptyline), ENDEP® (amitriptyline), FETZIMA® (levomilnacipran), KHEDEZLA® (desvenlafaxine), LATUDA® (lurasidone), LAMICTAL® (lamotrigine), LEXAPRO® (escitalopram), LIMBITROL® (amitriptyline and chlordiazepoxide), MARPLAN ® (isocarboxazid), NARDIL® (phenelzine), NORPRAMIN® (desipramine), OLEPTRO® (trazodone), PAMELOR® (nortriptyline), PARNATE® (tranylcypromine), PAXIL® (paroxetine), PEXEVA® (paroxetine), PROZAC® (fluoxetine), PRISTIQ® (desvenlafaxine), REMERON® (mirtazapine), SARAFEM® (fluoxetine), SEROQUEL XR® (quetiapine), SERZONE® (nefazodone), SINEQUAN® (doxepin), SURMONTIL® (trimipramine), SYMBYAX® (fluoxetine and the atypical antipsychotic drug olanzapine), TOFRANIL® (imipramine), TRIAVIL® (perphenazine and amitriptyline), VIIBRYD® (vilazodone), VIVACTIL® (protriptyline), WELLBUTRIN® (bupropion), ZOLOFT® (sertraline), or ZYPREXA® (olanzapine). In another embodiment, the antidepressant can be administered in a tablet dosage form. The tablet dosage form can comprise an amount of a antidepressant, or a pharmaceutically acceptable equivalent thereof, that can be 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 600 mg, 700 mg, 750 mg, 800 mg, 900 mg, or 1000 mg. In some embodiments, the antidepressant is administered in a tablet dosage form one to four times daily, and can be administered at least once a day for at least four weeks. In other embodiments, the antidepressant can be in the form of a modified release formulation.

[0058] Without limiting the present disclosure, a number of embodiments of the present disclosure are described below for purpose of illustration.

[0059] Embodiment 1: A method for diagnosing fibromyalgia in a patient comprising:

(a) obtaining an oxygenation level at a muscle location in the patient; and

(b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0060] Embodiment 2: The method of embodiment 1, wherein the muscle location in the patient is a trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle.

[0061] Embodiment s: The method of embodiment 2, wherein the muscle location in the patient is a trapezius muscle.

[0062] Embodiment 4: The method of any one of embodiments 1-3, wherein the muscle location in the patient comprises a first location, the method further comprising:

(a) obtaining an oxygenation level for the patient from a second muscle location;

(b) determining an average an oxygenation level based on the an oxygenation level measured at the first muscle location and the an oxygenation level measured at the second muscle location; and

(c) diagnosing fibromyalgia in the patient if the average an oxygenation level from the two muscle locations is lower than a threshold an oxygenation level.

[0063] Embodiment s: The method of any one of embodiments 1-4, further comprising: using the measured oxygenation level at the muscle location to associate the patient with one of a plurality of muscle tenderness categones. [0064] Embodiment 6: The method of embodiment 5, wherein the plurality' of muscle tenderness categories comprises three categories of mild, moderate, or extreme muscle tenderness.

[0065] Embodiment 7: The method of any one of embodiments 1-6, wherein the oxygenation level comprises a first oxygenation level, the method further comprising:

(a) providing a medication to the patient;

(b) obtaining a second oxygenation level from the patient from a second muscle location; and

(c) comparing the first oxygenation level to the second oxygenation level to determine whether the oxygenation level at the second muscle location has been reduced.

[0066] Embodiment 8: The method of embodiment 7, further comprising in response to a determination that the second oxygenation level at the second muscle location no longer is lower than the threshold oxygenation level, decreasing a dosage of the medication provided to the patient.

[0067] Embodiment 9: The method of embodiment 7, further comprising in response to a determination that the second oxygenation level at the second muscle location still is lower than the threshold oxygenation level, increasing a dosage of the medication provided to the patient.

[0068] Embodiment 10: The method of embodiment 7, further comprising in response to a determination that the second oxygenation level at the second muscle location still is lower than the threshold oxygenation level, maintaining a dosage of the medication provided to the patient.

[0069] Embodiment 1 1 : The method of embodiment 7, wherein the medication comprises a muscle relaxant.

[0070] Embodiment 12: A method for treating fibromyalgia in a patient comprising:

(a) obtaining an oxygenation level at a muscle location in the patient; and

(b) administering an effective amount of a muscle relaxant to the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0071] Embodiment 13: The method of embodiment 12, wherein the muscle location in the patient is a trapezius muscle, biceps brachn muscle, triceps brachn muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle. [0072] Embodiment 14: The method of embodiment 13, wherein the muscle location in the patient is a trapezius muscle.

[0073] Embodiment 15: A method of detecting an oxygenation level at a muscle location in a patient suspected of having fibromyalgia comprising:

(a) obtaining the oxygenation level at the muscle location in the patient; and

(b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level.

[0074] Embodiment 16: The method of embodiment 15, wherein the muscle location in the patient is a trapezius muscle, biceps brachn muscle, triceps brachn muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle.

[0075] Embodiment 17: A method for diagnosing and treating fibromyalgia in a patient comprising:

(a) obtaining an oxygenation level at a muscle location in the patient;

(b) diagnosing fibromyalgia in the patient if the oxygenation level at the muscle location is lower than a threshold oxygenation level; and

(c) administering an effective amount of a muscle relaxant to the diagnosed patient if the oxy genation level at the muscle location is lower than the threshold oxygenation level. [0076] Embodiment 18: The method of embodiment 17, wherein the muscle location in the patient is a trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle.

[0077] Embodiment 19: The method of embodiment 18, wherein the muscle location in the patient is a trapezius muscle.

[0078] Embodiment 20: A method for diagnosing fibromyalgia in a patient comprising:

(a) obtaining a muscle firmness at a muscle location in the patient; and

(b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0079] Embodiment 21 : The method of embodiment 20, wherein the muscle location in the patent is a trapezius muscle, biceps brachn muscle, triceps brachn muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle. [0080] Embodiment 22: The method of embodiment 21, wherein the muscle location in the patient is a trapezius muscle.

[0081] Embodiment 23 : The method of any one of embodiments 20-22, wherein the muscle location in the patient comprises a first location, the method further comprising:

(a) obtaining a muscle firmness for the patient from a second muscle location;

(b) determining an average a muscle firmness based on the a muscle firmness measured at the first muscle location and the a muscle firmness measured at the second muscle location; and

(c) diagnosing fibromyalgia in the patient if the average a muscle firmness from the two muscle locations exceeds a threshold a muscle firmness.

[0082] Embodiment 24: The method of any one of embodiments 20-23, further comprising: using the measured a muscle firmness at the muscle location to associate the patient with one of a plurality of muscle tenderness categories.

[0083] Embodiment 25 : The method of embodiment 24, wherein the plurality of muscle tenderness categories comprises three categories of mild, moderate, or extreme muscle tenderness.

[0084] Embodiment 26: The method of any one of embodiments 20-25, wherein the muscle firmness comprises a first muscle firmness, the method further comprising:

(a) providing a medication to the patient;

(b) obtaining a second muscle firmness from the patient from a second muscle location; and

(c) comparing the first muscle firmness to the second muscle firmness to determine whether the muscle firmness at the second muscle location has been reduced.

[0085] Embodiment 27 : The method of embodiment 26, further comprising in response to a determination that the second muscle firmness at the second muscle location no longer exceeds the threshold muscle firmness, decreasing a dosage of the medication provided to the patient.

[0086] Embodiment 28: The method of embodiment 26, further comprising in response to a determination that the second muscle firmness at the second muscle location still exceeds the threshold muscle firmness, increasing a dosage of the medication provided to the patient. [0087] Embodiment 29: The method of embodiment 26, further comprising in response to a determination that the second muscle firmness at the second muscle location still exceeds the threshold muscle firmness, maintaining a dosage of the medication provided to the patient.

[0088] Embodiment 30: The method of embodiment 26, wherein the medication comprises a muscle relaxant.

[0089] Embodiment 31 : A method for treating fibromyalgia in a patient comprising:

(a) obtaining a muscle firmness at a muscle location in the patient; and

(b) administering an effective amount of a muscle relaxant to the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0090] Embodiment 32: The method of embodiment 31, wherein the muscle location in the patient is a trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle.

[0091] Embodiment 33: The method of embodiment 31, wherein the muscle location in the patient is a trapezius muscle.

[0092] Embodiment 34: A method of detecting a muscle firmness at a muscle location in a patient suspected of having fibromyalgia comprising:

(a) obtaining the muscle firmness at the muscle location in the patient; and

(b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness.

[0093] Embodiment 35: The method of embodiment 34, wherein the muscle location in the patient is a trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle.

[0094] Embodiment 36: A method for diagnosing and treating fibromyalgia in a patient comprising:

(a) obtaining a muscle firmness at a muscle location in the patient;

(b) diagnosing fibromyalgia in the patient if the muscle firmness at the muscle location exceeds a threshold muscle firmness; and

(c) administering an effective amount of a muscle relaxant to the diagnosed patient if the muscle firmness at the muscle location exceeds the threshold muscle firmness. [0095] Embodiment 37: The method of embodiment 36, wherein the muscle location in the patient is a trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle.

[0096] Embodiment 38: The method of embodiment 37, wherein the muscle location in the patient is a trapezius muscle.

Examples

[0097] Example 1: Diagnosing fibromyalgia in patients by obtaining an oxygenation level at a muscle location in the patient.

[0098] Fibromyalgia (FM) is the most common diffuse chronic pain condition, its unknown pathophysiological mechanism leads to a lack of diagnostics and to a lack of effective therapies. New, non-invasive diagnostic methods are developed herein to better diagnose FM and to advance the current knowledge pertaining to the pathophysiology of FM. For this study, spectroscopy (e.g., near infrared spectroscopy; NIRS) is used to measure oxygenation levels in muscle (muscle hypoxia) of FM patients. The study simultaneously observes muscle tenderness, muscle firmness and stiffness in FM patients compared to non-rheumatic disease controls to further provide an analysis of the physical differences in FM.

[0099] Muscle oxygenation levels are determined in FM patients using NIRS, and compared to muscle oxygenation levels in control patients (control patients can be patients with a non-rheumatic disease, patients with another rheumatic disease other than fibromyalgia, or healthy patients). Muscle oxygenation levels are determined at one or more muscle locations. For example, the trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle. Muscle tenderness is also noted using, for example, the three categories of mild, moderate, or extreme muscle tenderness. Decreased muscle oxygen levels are observed in FM patients compared to control patients.

[00100] Example 2: Diagnosing fibromyalgia in patients by obtaining a muscle firmness at a muscle location in the patient.

[00101] Fibromyalgia (FM) is the most common diffuse chronic pain condition, its unknown pathophysiological mechanism leads to a lack of diagnostics and to a lack of effective therapies. New, non-invasive diagnostic methods are developed herein to better diagnose FM and to advance the current knowledge pertaining to the pathophysiology of FM. For this study, shear wave ultrasound is used to measure muscle firmness in FM patients. The study simultaneously observes muscle tenderness and stiffness in FM patients compared to nonrheumatic disease controls to further provide an analysis of the physical differences in FM.

[00102] Muscle firmness is determined in FM patients using shear wave ultrasound, and compared to muscle firmness in control patients (control patients can be patients with a nonrheumatic disease, patients with another rheumatic disease other than fibromyalgia, or healthy patients). Muscle firmness is determined at one or more muscle locations. For example, the trapezius muscle, biceps brachii muscle, triceps brachii muscle, pectoralis major muscle, deltoideus muscle, gastrocnemius muscle, soleus muscle, quadriceps femoris muscle, gluteus maximus muscle, or rectus femoris muscle. Muscle tenderness is also noted using, for example, the three categories of mild, moderate, or extreme muscle tenderness. Increased muscle firmness is observed in FM patients compared to control patients.

[00103] While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope being indicated by the following claims, along with the full scope of equivalents to which such claims are entitled. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[00104] Because many modifications, variations, and changes in detail can be made to the described example, it is intended that all matters in the preceding description and shown in the accompanying figures be interpreted as illustrative and not in a limiting sense. Further, it is intended to be understood that the following clauses (and any combination of the clauses) further describe aspects of the present description.