Non-invasive ph-dependent imaging using quantitative chemical exchange saturation transfer (qcest)

Abstract

In various embodiments, the invention teaches systems and methods for magnetic resonance imaging. In some embodiments, the invention teaches systems and methods for determining the source of pain in intervertebral discs by measuring one or more physiological biomarkers associated with disc pain and/or disc degeneration.

1 .- 25 . (canceled) 
     
     
         26 . A method for treating a subject diagnosed with a condition, comprising:
 administering a treatment to a subject diagnosed with a condition, wherein the subject was diagnosed with the condition by a method comprising:
 performing a scan of a region of the subject's body using a magnetic resonance imaging (MRI) scanner; 
 generating an image of the region of the subject's body from the performed scan using a quantitative chemical exchange saturation transfer (qCEST) sequence; 
 processing the image to detect one or more physiological biomarkers within the image of the region,
 wherein the physiological biomarkers comprise a labile proton exchange rate (k SW ) between a solute pool and a water pool; and 
 
 determining that the subject has the condition if the labile proton exchange rate is increased relative to a reference value,
 wherein the increased labile proton exchange rate is greater than 200 exchanges/second. 
 
   
     
     
         27 . The method of  claim 26 , wherein the increased labile proton exchange rate is correlated to a low pH value. 
     
     
         28 . The method of  claim 26 , wherein the increased labile proton exchange rate is from 201 to 1000 exchanges/second. 
     
     
         29 . The method of  claim 27 , wherein the low pH value is from 5.6 to 6.99. 
     
     
         30 . The method of  claim 26 , wherein the reference value is a reference labile proton exchange rate, wherein the reference labile proton exchange rate is from 100 to 200 exchanges/second. 
     
     
         31 . The method of  claim 30 , wherein the reference labile proton exchange rate is correlated to a reference pH value. 
     
     
         32 . The method of  claim 31 , wherein the reference pH value is from 7.0 to 7.2. 
     
     
         33 . The method of  claim 26 , wherein the condition is intervertebral disc degeneration, discogenic pain, discogenic low back pain, chronic low back pain, low back pain, back pain, chronic back pain, progressive intervertebral disc degeneration, osteoarthritis, rheumatoid arthritis, an articular cartilage injury, or temporomandibular disc degeneration, or combinations thereof. 
     
     
         34 . The method of  claim 26 , wherein the region of the subject's body comprises a joint or an intervertebral disc. 
     
     
         35 . The method of  claim 26 , wherein the condition is a painful condition. 
     
     
         36 . The method of  claim 26 , wherein the increased labile proton exchange rate is correlated with an upregulation of one or more pain-related factors in the subject. 
     
     
         37 . The method of  claim 36 , wherein the one or more pain-related factors are bradykinin receptor B 1  (BDKRB 1 ), calcitonin gene-related peptide (CGRP), or catechol-0-methyltransferase (COMT). 
     
     
         38 . The method of  claim 26 , wherein the increased labile proton exchange rate is correlated with an upregulation of one or more inflammation-related factors in the subject. 
     
     
         39 . The method of  claim 38 , wherein the inflammation-related factor is interleukin-6 (IL-6). 
     
     
         40 . The method of  claim 26 , wherein the increased labile proton exchange rate is correlated with an upregulation of one or more neurogenic factors in the subject. 
     
     
         41 . The method of  claim 40 , wherein the neurogenic factor is brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF). 
     
     
         42 . The method of  claim 26 , wherein the quantitative chemical exchange saturation transfer (qCEST) sequence is a two dimension (2D) quantitative chemical exchange saturation transfer (qCEST) sequence, or a three dimension (3D) quantitative chemical exchange saturation transfer (qCEST) sequence. 
     
     
         43 . The method of  claim 26 , wherein the treatment is a pharmacological treatment, a biological treatment, a cell treatment, a gene therapy, an interventional surgical treatment, or combinations thereof. 
     
     
         44 . The method of  claim 26 , further comprising determining that an origin of the subject's condition is within the region of the subject's body where the physiological biomarker was measured. 
     
     
         45 . The method of  claim 27 , wherein the low pH value is indicative of the subject having the condition. 
     
     
         46 . The method of  claim 26 , further comprising selecting the treatment prior to administering the treatment.