<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03299361</url>
  </required_header>
  <id_info>
    <org_study_id>TSGHIRB 1-105-05-056</org_study_id>
    <nct_id>NCT03299361</nct_id>
  </id_info>
  <brief_title>Diffusion Tensor Imaging of the Median Nerve Before and After Carpal Tunnel Corticosteroid Injection in Patients With Carpal Tunnel Syndrome: Feasibility Study</brief_title>
  <official_title>Diffusion Tensor Imaging of the Median Nerve Before and After Carpal Tunnel Corticosteroid Injection in Patients With Carpal Tunnel Syndrome: Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tri-Service General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tri-Service General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Carpal tunnel syndrome (CTS) is the most common nerve compression disorder in the upper&#xD;
      extremity. Therapy for carpal tunnel syndrome includes physical and occupational therapy, the&#xD;
      use of splints and other local measures, and corticosteroid injection into the carpal tunnel.&#xD;
      When these measures fail, open surgical release is considered the next step. Although the&#xD;
      main disadvantage of corticosteroid injection is that symptoms are often short-lived relief&#xD;
      and partial relief, it may not provide a permanent solution, corticosteroid injections are&#xD;
      chosen because of lower level of invasiveness, faster recovery, and ease of the technique.&#xD;
&#xD;
      Diffusion tensor magnetic resonance imaging (DTI) reveals tissue microstructure based on&#xD;
      random movements of water molecules. The measured diffusion-weighted images are further&#xD;
      analyzed for parameter images that describe different characteristics of diffusion: apparent&#xD;
      diffusion coefficient (ADC) is an absolute measure of the strength of diffusion, and&#xD;
      fractional anisotropy (FA) describes the asymmetry of the diffusion direction due to tissue&#xD;
      structures. Because the axonal cell membrane and the myelin sheath in nerve fibers prevent&#xD;
      diffusion in the direction which is perpendicular to their fascicles, resulting in the&#xD;
      isotropy of the diffusion of water molecules being lost. DTI is the only method which can&#xD;
      give an indirect view of the microstructure of nervous tissue in addition to the pathway of&#xD;
      the fibers.&#xD;
&#xD;
      DTI has been applied to study peripheral nerves, to demonstrate the feasibility of the method&#xD;
      and to study nerve entrapment in carpal tunnel syndrome (CTS). The previous studies have&#xD;
      demonstrated a decrease in FA in patients with CTS compared to healthy volunteers. The DTI&#xD;
      parameters of the median nerve have revealed significant increase of FA and decrease in ADC&#xD;
      with complete symptom relief 6 months after carpal tunnel release. However, Hiltunen et al.&#xD;
      have demonstrated a significant decrease in ADC but no alter in FA in patients received open&#xD;
      carpal tunnel release 1 year later and felt complete symptoms relief. By means of open carpal&#xD;
      tunnel release, follow-up recordings were made at least 6 months after the operation to&#xD;
      ensure time for post-operative tissue recovery. As a result, the investigators still do not&#xD;
      understand the relevance between the parameters of DTI to symptoms relief in CTS patients&#xD;
      receiving conservative treatment.&#xD;
&#xD;
      Different from carpal tunnel release, steroid injections are popular technique for CTS&#xD;
      treatment and are believed to reduce perineural inﬂammation or soft tissue swelling, and may&#xD;
      stabilize the neural membrane, thus limiting the ephaptic transmission in ischemic nerve&#xD;
      ﬁbers which causes symptoms. Corticosteroid injections can provide a rapid symptom relief at&#xD;
      2 weeks follow up. However, there is no report addressing the relation of functional change&#xD;
      of median nerve at several anatomic locations to the symptom relief of CTS. Here the&#xD;
      investigators monitored, by means of DTI, median nerve integrity in CTS patients before and&#xD;
      after corticosteroid injection. This information may help to explain the hypothesis regarding&#xD;
      the effect of corticosteroid to the median nerve, to identify which anatomic location of&#xD;
      median nerve relevant to the symptom relief of CTS after corticosteroid injection, and be&#xD;
      useful for the clinical follow-up of patients with nerve entrapments following conservative&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study subjects This study was approved by the institutional research ethics board. Written&#xD;
      informed consent was prospectively obtained from all study subjects. Twelve consecutive&#xD;
      patients (nine females, three male; mean age, 56 years; range, 38 to 76 years) suffering from&#xD;
      bilateral CTS referred for consideration of carpal tunnel steroid injection were&#xD;
      prospectively recruited. Inclusion criteria consisted of a clinical diagnosis of unilateral&#xD;
      or bilateral CTS based on a standardized and validated diagnostic scale. The degree of the&#xD;
      entrapment ranged from mild to severe according to the American Association of&#xD;
      Electrodiagnostic Medicine ratings: mild = slowing of sensory conduction velocity (&lt;50 m/s),&#xD;
      moderate = slowing of sensory conduction velocity (&lt;50 m/s) and delayed motor distal latency&#xD;
      (&gt;4 ms), and severe = absence of sensory response. Exclusion criteria included prior carpal&#xD;
      tunnel release or contraindications to MRI. All patients also had the clinical diagnosis&#xD;
      supported by electrodiagnostic investigations.&#xD;
&#xD;
      Ultrasound needle guidance:&#xD;
&#xD;
      The US-guided injection procedure was performed in a standardized manner. The one-needle&#xD;
      two-syringe technique with US guidance was used (1) one needle is used for anesthesia,&#xD;
      hydrodissection, and intra-carpal tunnel injection; (2) the first syringe is used to&#xD;
      anesthetize, hydrodissect, and dilate the intra-carpal tunnel space; and (3) the second&#xD;
      syringe is used to inject the corticosteroid therapy into the new hydrodissected space. After&#xD;
      hydrodissection, the empty lidocaine syringe was detached from the needle while still in the&#xD;
      carpal tunnel, and a 3-ml syringe prefilled with 10 mg triamcinolone acetonide suspension was&#xD;
      attached to the indwelling needle, and the treatment was slowly injected into the&#xD;
      hydrodissected neutral space. The injections were performed in a standardized fashion by a&#xD;
      musculoskeletal radiologist (Y.C.H.) with 13 years of experience in US.&#xD;
&#xD;
      MRI protocol Magnetic resonance images were acquired at 3.0 T (Discovery MR750, GE&#xD;
      Healthcare, Milwaukee, WI, USA) using a 8-channel wrist coil (GE Healthcare, Gainesville, FL,&#xD;
      USA). The coil was at the center of the magnet to maximize the magnetic-field homogeneity.&#xD;
      The subject's hand was fixed with a plastic plate and Velcro tape to the coil to restrict&#xD;
      movements; the subjects were examined in prone position.&#xD;
&#xD;
      For DTI, the investigators recorded non-diffusion-weighted b0 image and 15 diffusion gradient&#xD;
      directions with b = 1,200 s/mm2 from 20 axial slices of 4 mm thickness. Slices were&#xD;
      positioned to cover the whole carpal tunnel and in part the proximal and distal nerve. The&#xD;
      two most proximal and distal slices were excluded from the analysis because of potential bias&#xD;
      caused by the rapid decrease in homogeneity at the edge of the coil. Thus, the total&#xD;
      proximal-distal range examined was 80 mm. The other imaging parameters were as follows:&#xD;
      repetition time (TR) = 10,000 ms, echo time (TE) = 101 ms, number of averages = 3 (during&#xD;
      post-processing), field of view (FOV) = 12 cm and matrix 100 × 80 pixels. The voxel size was&#xD;
      thus 1.46 × 1.46 ×4 mm3.&#xD;
&#xD;
      In addition to DTI, the imaging protocol comprised the following MRI sequences:&#xD;
&#xD;
        1. Axial T2-weighted fast spin echo (FSE): TR = 5,430 ms, TE = 88 ms, echo train length&#xD;
           (ETL) = 16, FOV = 12 cm, matrix 224 × 256 pixels, phase FOV = 0.7, the same slice&#xD;
           positions as in DTI.&#xD;
&#xD;
        2. Axial T1-weighted fast spin echo (FSE): TR = 457 ms, TE = 11~33 ms, flip angle = 110°,&#xD;
           FOV = 12 cm, matrix 384 × 256 pixels, phase FOV = 0.7, the same slice positions as in&#xD;
           DTI.&#xD;
&#xD;
      Data collection:&#xD;
&#xD;
      The patients' medical records were reviewed by a neurologist (F.C.Y.). Routinely, the&#xD;
      investigators recorded clinical data (including sex, age, and side of injection, and the&#xD;
      effect of treatment. The satisfaction scale of patients was rated using a Likert scale: 5 =&#xD;
      greatly satisfactory; 4 = some residual symptoms and satisfaction &gt; 50%; 3 = some residual&#xD;
      symptoms and satisfaction = 50% ; 2 = residual symptoms and satisfaction &lt; 50%; 1=&#xD;
      unsatisfactory. Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) is the most commonly used&#xD;
      questionnaire for the measurement of the severity of symptoms and functional status with&#xD;
      reproducibility, internal consistency, and validity in patients with CTS. The symptom&#xD;
      severity subscale of BCTQ consists of 11 questions with scores from 1 point (mildest) to 5&#xD;
      points (most severe), and the functional status of BCTQ subscale is made up of 8 questions&#xD;
      with scores from 1 point (no difficulty in activity) to 5 points (unable to perform the&#xD;
      activity at all). Patients were seen in the subsequent clinical visit to determine outcomes.&#xD;
      The investigators also recorded the decrement of BCTQ between the pre-injection and&#xD;
      post-injection.&#xD;
&#xD;
      Data analysis Two investigators (Y.C.H., H.Y.C.) with experience in peripheral nerve imaging&#xD;
      assessed the quality of the DTI source data. No case with visible motion artefacts was&#xD;
      identified. Eddy current induced distortion occasionally appeared on the very proximal&#xD;
      imaging planes, but did not affect the measurement regions. The DTI source data was post&#xD;
      processed using the commercial post-processing workstation (GE Healthcare, ADW4.5). The&#xD;
      investigators blinded to clinical data, side, and time point relative to steroid injection&#xD;
      randomly performed all measurements. The same author performed a second blinded analysis of&#xD;
      all acquired datasets after a 2-week period. Raw DTI data was initially reviewed with regard&#xD;
      to image quality and occurrence of artefacts. After performing the GE Workspace imaging&#xD;
      co-registration of EPI images for motion correction (through plane), DTI-based tractography&#xD;
      (DTT) of the median nerve was performed. By defining at least two seed points, fibers passing&#xD;
      in anterograde and retrograde direction followed a streamline algorithm and terminated if FA&#xD;
      values were below 0.15 or if there were angle changes over 27°. The median nerve was&#xD;
      visualized using at least three different attempts with two ROIs placed at different slice&#xD;
      positions along the nerve (covering the entire imaged carpal tunnel). The 3D course of the&#xD;
      nerve was tracked with DTT computed with the FACT algorithm (Fiber Assignment by Continuous&#xD;
      Tracking).&#xD;
&#xD;
      Fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured&#xD;
      bilaterally at each time point. FA and ADC were calculated from free-hand regions of interest&#xD;
      (ROIs) placed in the center of the median nerve at three levels: at the level of the distal&#xD;
      radioulnar joint (the most proximal slice where by the distal radio ulnar joint was&#xD;
      visualized) and at the level of the flexor retinaculum (level of the pisiform). To avoid&#xD;
      partial volume artifacts, care was taken to draw the ROIs slightly smaller than the&#xD;
      cross-sectional area of the median nerve. The size of the ROIs depended on the&#xD;
      cross-sectional area of the nerve and all ROIs were placed on one slice only. Anatomic&#xD;
      reference images were used to identify the median nerve. The measurement of each parameter&#xD;
      was repeated three times and the mean was calculated. Representative images are presented.&#xD;
&#xD;
      Regarding the assessment of DTT, the investigators determined the nerve fiber tractography by&#xD;
      morphology. Four different nerve trajectory patterns were defined by Breitenseher et al.: (1)&#xD;
      If there was no alteration of the peripheral nerve trajectories, the pattern was rated&#xD;
      &quot;continuous&quot;. (2) If the trajectories were continuous, but irregularly organized, peripheral&#xD;
      nerve tractography result was rated &quot;deranged&quot; .(3) In cases where only some of the ulnar&#xD;
      nerve trajectories were interrupted in one peripheral nerve segment, the finding was defined&#xD;
      as &quot;partially discontinuous &quot;. (4) If there was a complete discontinuity of all trajectories&#xD;
      and a &quot;gap&quot; on at least one plane, tractography was classified as &quot;completely discontinuous&quot;.&#xD;
      DTT images were evaluated by two readers (Y.C.H., G.S.H.) in consensus.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 26, 2016</start_date>
  <completion_date type="Actual">March 7, 2017</completion_date>
  <primary_completion_date type="Actual">December 31, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Inter-scan change of DTI at baseline and 2 weeks after injection</measure>
    <time_frame>February, 2017</time_frame>
    <description>The DTI values for each wrist at baseline were compared to the DTI of the same wrist at 2 weeks in individual patients. DTI parameters: FA (numeric; unit free), ADC (numeric; unit: mm2/s), and DTT (morphology, unit free); BCTQ (numeric; unit free)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation of Inter-scan change of DTI with symptoms relief</measure>
    <time_frame>February, 2017</time_frame>
    <description>The investigators determined the inter-scan correlation between increment of DTI parameters and the decrement of BCTQ. DTI parameters: FA (numeric; unit free), ADC (numeric; unit: mm2/s), and DTT (morphology, unit free); BCTQ (numeric; unit free)</description>
  </primary_outcome>
  <enrollment type="Actual">12</enrollment>
  <condition>Carpal Tunnel Syndrome</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Magnetic resonance image (MRI)</intervention_name>
    <description>Diffusion tensor magnetic resonance imaging (DTI) of MRI reveals tissue microstructure based on random movements of water molecules. Here we monitored, by means of DTI, median nerve integrity in CTS patients before and after corticosteroid injection. This information may help to explain the hypothesis regarding the effect of corticosteroid to the median nerve, to identify which anatomic location of median nerve relevant to the symptom relief of CTS after corticosteroid injection, and be useful for the clinical follow-up of patients with nerve entrapments following conservative treatment.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        1. All patients had the clinical diagnosis supported by electrodiagnostic investigations.&#xD;
&#xD;
          2. All patients underwent US-guided corticosteroid injection of median nerve and received&#xD;
             MR study before and after the injection.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  clinical diagnosis of unilateral or bilateral CTS based on a standardized and&#xD;
             validated diagnostic scale&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  prior carpal tunnel release or contraindications to MRI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yi-Chih Hsu, M.D</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Radiology, Tri-Service General Hospital, National Defense Medical Center</affiliation>
  </overall_official>
  <results_reference>
    <citation>Stevens JC, Sun S, Beard CM, O'Fallon WM, Kurland LT. Carpal tunnel syndrome in Rochester, Minnesota, 1961 to 1980. Neurology. 1988 Jan;38(1):134-8. doi: 10.1212/wnl.38.1.134.</citation>
    <PMID>3336444</PMID>
  </results_reference>
  <results_reference>
    <citation>Katz JN, Simmons BP. Clinical practice. Carpal tunnel syndrome. N Engl J Med. 2002 Jun 6;346(23):1807-12. doi: 10.1056/NEJMcp013018. No abstract available.</citation>
    <PMID>12050342</PMID>
  </results_reference>
  <results_reference>
    <citation>Gonzalez MH, Bylak J. Steroid injection and splinting in the treatment of carpal tunnel syndrome. Orthopedics. 2001 May;24(5):479-81. doi: 10.3928/0147-7447-20010501-16.</citation>
    <PMID>11379997</PMID>
  </results_reference>
  <results_reference>
    <citation>Jarvik JG, Comstock BA, Kliot M, Turner JA, Chan L, Heagerty PJ, Hollingworth W, Kerrigan CL, Deyo RA. Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial. Lancet. 2009 Sep 26;374(9695):1074-81. doi: 10.1016/S0140-6736(09)61517-8.</citation>
    <PMID>19782873</PMID>
  </results_reference>
  <results_reference>
    <citation>Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J. 1994 Jan;66(1):259-67. doi: 10.1016/S0006-3495(94)80775-1.</citation>
    <PMID>8130344</PMID>
  </results_reference>
  <results_reference>
    <citation>Le Bihan D. Molecular diffusion, tissue microdynamics and microstructure. NMR Biomed. 1995 Nov-Dec;8(7-8):375-86. doi: 10.1002/nbm.1940080711.</citation>
    <PMID>8739274</PMID>
  </results_reference>
  <results_reference>
    <citation>Basser PJ, Jones DK. Diffusion-tensor MRI: theory, experimental design and data analysis - a technical review. NMR Biomed. 2002 Nov-Dec;15(7-8):456-67. doi: 10.1002/nbm.783.</citation>
    <PMID>12489095</PMID>
  </results_reference>
  <results_reference>
    <citation>Basser PJ, Pierpaoli C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B. 1996 Jun;111(3):209-19. doi: 10.1006/jmrb.1996.0086.</citation>
    <PMID>8661285</PMID>
  </results_reference>
  <results_reference>
    <citation>Hiltunen J, Suortti T, Arvela S, Seppa M, Joensuu R, Hari R. Diffusion tensor imaging and tractography of distal peripheral nerves at 3 T. Clin Neurophysiol. 2005 Oct;116(10):2315-23. doi: 10.1016/j.clinph.2005.05.014.</citation>
    <PMID>16125460</PMID>
  </results_reference>
  <results_reference>
    <citation>Skorpil M, Karlsson M, Nordell A. Peripheral nerve diffusion tensor imaging. Magn Reson Imaging. 2004 Jun;22(5):743-5. doi: 10.1016/j.mri.2004.01.073.</citation>
    <PMID>15172070</PMID>
  </results_reference>
  <results_reference>
    <citation>Kabakci N, Gurses B, Firat Z, Bayram A, Ulug AM, Kovanlikaya A, Kovanlikaya I. Diffusion tensor imaging and tractography of median nerve: normative diffusion values. AJR Am J Roentgenol. 2007 Oct;189(4):923-7. doi: 10.2214/AJR.07.2423.</citation>
    <PMID>17885066</PMID>
  </results_reference>
  <results_reference>
    <citation>Khalil C, Hancart C, Le Thuc V, Chantelot C, Chechin D, Cotten A. Diffusion tensor imaging and tractography of the median nerve in carpal tunnel syndrome: preliminary results. Eur Radiol. 2008 Oct;18(10):2283-91. doi: 10.1007/s00330-008-0971-4. Epub 2008 Apr 17.</citation>
    <PMID>18418602</PMID>
  </results_reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>September 30, 2017</last_update_submitted>
  <last_update_submitted_qc>September 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tri-Service General Hospital</investigator_affiliation>
    <investigator_full_name>yi-chih HSU</investigator_full_name>
    <investigator_title>Radiologist</investigator_title>
  </responsible_party>
  <keyword>Carpal tunnel syndrome</keyword>
  <keyword>Corticosteroid</keyword>
  <keyword>Diffusion tensor imaging</keyword>
  <keyword>Injection</keyword>
  <keyword>Magnetic resonance image</keyword>
  <keyword>Ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carpal Tunnel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>November 10, 2017</submitted>
    <returned>August 15, 2018</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03299361
org study id: TSGHIRB 1-105-05-056
nct id: NCT03299361
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Carpal tunnel syndrome (CTS) is the most common nerve compression disorder in the upper
      extremity. Therapy for carpal tunnel syndrome includes physical and occupational therapy, the
      use of splints and other local measures, and corticosteroid injection into the carpal tunnel.
      When these measures fail, open surgical release is considered the next step. Although the
      main disadvantage of corticosteroid injection is that symptoms are often short-lived relief
      and partial relief, it may not provide a permanent solution, corticosteroid injections are
      chosen because of lower level of invasiveness, faster recovery, and ease of the technique.

      Diffusion tensor magnetic resonance imaging (DTI) reveals tissue microstructure based on
      random movements of water molecules. The measured diffusion-weighted images are further
      analyzed for parameter images that describe different characteristics of diffusion: apparent
      diffusion coefficient (ADC) is an absolute measure of the strength of diffusion, and
      fractional anisotropy (FA) describes the asymmetry of the diffusion direction due to tissue
      structures. Because the axonal cell membrane and the myelin sheath in nerve fibers prevent
      diffusion in the direction which is perpendicular to their fascicles, resulting in the
      isotropy of the diffusion of water molecules being lost. DTI is the only method which can
      give an indirect view of the microstructure of nervous tissue in addition to the pathway of
      the fibers.

      DTI has been applied to study peripheral nerves, to demonstrate the feasibility of the method
      and to study nerve entrapment in carpal tunnel syndrome (CTS). The previous studies have
      demonstrated a decrease in FA in patients with CTS compared to healthy volunteers. The DTI
      parameters of the median nerve have revealed significant increase of FA and decrease in ADC
      with complete symptom relief 6 months after carpal tunnel release. However, Hiltunen et al.
      have demonstrated a significant decrease in ADC but no alter in FA in patients received open
      carpal tunnel release 1 year later and felt complete symptoms relief. By means of open carpal
      tunnel release, follow-up recordings were made at least 6 months after the operation to
      ensure time for post-operative tissue recovery. As a result, the investigators still do not
      understand the relevance between the parameters of DTI to symptoms relief in CTS patients
      receiving conservative treatment.

      Different from carpal tunnel release, steroid injections are popular technique for CTS
      treatment and are believed to reduce perineural inﬂammation or soft tissue swelling, and may
      stabilize the neural membrane, thus limiting the ephaptic transmission in ischemic nerve
      ﬁbers which causes symptoms. Corticosteroid injections can provide a rapid symptom relief at
      2 weeks follow up. However, there is no report addressing the relation of functional change
      of median nerve at several anatomic locations to the symptom relief of CTS. Here the
      investigators monitored, by means of DTI, median nerve integrity in CTS patients before and
      after corticosteroid injection. This information may help to explain the hypothesis regarding
      the effect of corticosteroid to the median nerve, to identify which anatomic location of
      median nerve relevant to the symptom relief of CTS after corticosteroid injection, and be
      useful for the clinical follow-up of patients with nerve entrapments following conservative
      treatment.
Study subjects This study was approved by the institutional research ethics board. Written
      informed consent was prospectively obtained from all study subjects. Twelve consecutive
      patients (nine females, three male; mean age, 56 years; range, 38 to 76 years) suffering from
      bilateral CTS referred for consideration of carpal tunnel steroid injection were
      prospectively recruited. Inclusion criteria consisted of a clinical diagnosis of unilateral
      or bilateral CTS based on a standardized and validated diagnostic scale. The degree of the
      entrapment ranged from mild to severe according to the American Association of
      Electrodiagnostic Medicine ratings: mild = slowing of sensory conduction velocity (<50 m/s),
      moderate = slowing of sensory conduction velocity (<50 m/s) and delayed motor distal latency
      (>4 ms), and severe = absence of sensory response. Exclusion criteria included prior carpal
      tunnel release or contraindications to MRI. All patients also had the clinical diagnosis
      supported by electrodiagnostic investigations.

      Ultrasound needle guidance:

      The US-guided injection procedure was performed in a standardized manner. The one-needle
      two-syringe technique with US guidance was used (1) one needle is used for anesthesia,
      hydrodissection, and intra-carpal tunnel injection; (2) the first syringe is used to
      anesthetize, hydrodissect, and dilate the intra-carpal tunnel space; and (3) the second
      syringe is used to inject the corticosteroid therapy into the new hydrodissected space. After
      hydrodissection, the empty lidocaine syringe was detached from the needle while still in the
      carpal tunnel, and a 3-ml syringe prefilled with 10 mg triamcinolone acetonide suspension was
      attached to the indwelling needle, and the treatment was slowly injected into the
      hydrodissected neutral space. The injections were performed in a standardized fashion by a
      musculoskeletal radiologist (Y.C.H.) with 13 years of experience in US.

      MRI protocol Magnetic resonance images were acquired at 3.0 T (Discovery MR750, GE
      Healthcare, Milwaukee, WI, USA) using a 8-channel wrist coil (GE Healthcare, Gainesville, FL,
      USA). The coil was at the center of the magnet to maximize the magnetic-field homogeneity.
      The subject's hand was fixed with a plastic plate and Velcro tape to the coil to restrict
      movements; the subjects were examined in prone position.

      For DTI, the investigators recorded non-diffusion-weighted b0 image and 15 diffusion gradient
      directions with b = 1,200 s/mm2 from 20 axial slices of 4 mm thickness. Slices were
      positioned to cover the whole carpal tunnel and in part the proximal and distal nerve. The
      two most proximal and distal slices were excluded from the analysis because of potential bias
      caused by the rapid decrease in homogeneity at the edge of the coil. Thus, the total
      proximal-distal range examined was 80 mm. The other imaging parameters were as follows:
      repetition time (TR) = 10,000 ms, echo time (TE) = 101 ms, number of averages = 3 (during
      post-processing), field of view (FOV) = 12 cm and matrix 100 × 80 pixels. The voxel size was
      thus 1.46 × 1.46 ×4 mm3.

      In addition to DTI, the imaging protocol comprised the following MRI sequences:

        1. Axial T2-weighted fast spin echo (FSE): TR = 5,430 ms, TE = 88 ms, echo train length
           (ETL) = 16, FOV = 12 cm, matrix 224 × 256 pixels, phase FOV = 0.7, the same slice
           positions as in DTI.

        2. Axial T1-weighted fast spin echo (FSE): TR = 457 ms, TE = 11~33 ms, flip angle = 110°,
           FOV = 12 cm, matrix 384 × 256 pixels, phase FOV = 0.7, the same slice positions as in
           DTI.

      Data collection:

      The patients' medical records were reviewed by a neurologist (F.C.Y.). Routinely, the
      investigators recorded clinical data (including sex, age, and side of injection, and the
      effect of treatment. The satisfaction scale of patients was rated using a Likert scale: 5 =
      greatly satisfactory; 4 = some residual symptoms and satisfaction > 50%; 3 = some residual
      symptoms and satisfaction = 50% ; 2 = residual symptoms and satisfaction < 50%; 1=
      unsatisfactory. Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) is the most commonly used
      questionnaire for the measurement of the severity of symptoms and functional status with
      reproducibility, internal consistency, and validity in patients with CTS. The symptom
      severity subscale of BCTQ consists of 11 questions with scores from 1 point (mildest) to 5
      points (most severe), and the functional status of BCTQ subscale is made up of 8 questions
      with scores from 1 point (no difficulty in activity) to 5 points (unable to perform the
      activity at all). Patients were seen in the subsequent clinical visit to determine outcomes.
      The investigators also recorded the decrement of BCTQ between the pre-injection and
      post-injection.

      Data analysis Two investigators (Y.C.H., H.Y.C.) with experience in peripheral nerve imaging
      assessed the quality of the DTI source data. No case with visible motion artefacts was
      identified. Eddy current induced distortion occasionally appeared on the very proximal
      imaging planes, but did not affect the measurement regions. The DTI source data was post
      processed using the commercial post-processing workstation (GE Healthcare, ADW4.5). The
      investigators blinded to clinical data, side, and time point relative to steroid injection
      randomly performed all measurements. The same author performed a second blinded analysis of
      all acquired datasets after a 2-week period. Raw DTI data was initially reviewed with regard
      to image quality and occurrence of artefacts. After performing the GE Workspace imaging
      co-registration of EPI images for motion correction (through plane), DTI-based tractography
      (DTT) of the median nerve was performed. By defining at least two seed points, fibers passing
      in anterograde and retrograde direction followed a streamline algorithm and terminated if FA
      values were below 0.15 or if there were angle changes over 27°. The median nerve was
      visualized using at least three different attempts with two ROIs placed at different slice
      positions along the nerve (covering the entire imaged carpal tunnel). The 3D course of the
      nerve was tracked with DTT computed with the FACT algorithm (Fiber Assignment by Continuous
      Tracking).

      Fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured
      bilaterally at each time point. FA and ADC were calculated from free-hand regions of interest
      (ROIs) placed in the center of the median nerve at three levels: at the level of the distal
      radioulnar joint (the most proximal slice where by the distal radio ulnar joint was
      visualized) and at the level of the flexor retinaculum (level of the pisiform). To avoid
      partial volume artifacts, care was taken to draw the ROIs slightly smaller than the
      cross-sectional area of the median nerve. The size of the ROIs depended on the
      cross-sectional area of the nerve and all ROIs were placed on one slice only. Anatomic
      reference images were used to identify the median nerve. The measurement of each parameter
      was repeated three times and the mean was calculated. Representative images are presented.

      Regarding the assessment of DTT, the investigators determined the nerve fiber tractography by
      morphology. Four different nerve trajectory patterns were defined by Breitenseher et al.: (1)
      If there was no alteration of the peripheral nerve trajectories, the pattern was rated
      "continuous". (2) If the trajectories were continuous, but irregularly organized, peripheral
      nerve tractography result was rated "deranged" .(3) In cases where only some of the ulnar
      nerve trajectories were interrupted in one peripheral nerve segment, the finding was defined
      as "partially discontinuous ". (4) If there was a complete discontinuity of all trajectories
      and a "gap" on at least one plane, tractography was classified as "completely discontinuous".
      DTT images were evaluated by two readers (Y.C.H., G.S.H.) in consensus.
observational model: Case-Only
time perspective: Prospective
measure: Inter-scan change of DTI at baseline and 2 weeks after injection
time frame: February, 2017
description: The DTI values for each wrist at baseline were compared to the DTI of the same wrist at 2 weeks in individual patients. DTI parameters: FA (numeric; unit free), ADC (numeric; unit: mm2/s), and DTT (morphology, unit free); BCTQ (numeric; unit free)
measure: Correlation of Inter-scan change of DTI with symptoms relief
time frame: February, 2017
description: The investigators determined the inter-scan correlation between increment of DTI parameters and the decrement of BCTQ. DTI parameters: FA (numeric; unit free), ADC (numeric; unit: mm2/s), and DTT (morphology, unit free); BCTQ (numeric; unit free)
intervention type: Other
intervention name: Magnetic resonance image (MRI)
description: Diffusion tensor magnetic resonance imaging (DTI) of MRI reveals tissue microstructure based on random movements of water molecules. Here we monitored, by means of DTI, median nerve integrity in CTS patients before and after corticosteroid injection. This information may help to explain the hypothesis regarding the effect of corticosteroid to the median nerve, to identify which anatomic location of median nerve relevant to the symptom relief of CTS after corticosteroid injection, and be useful for the clinical follow-up of patients with nerve entrapments following conservative treatment.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Yi-Chih Hsu, M.D
role: Study Chair
affiliation: Department of Radiology, Tri-Service General Hospital, National Defense Medical Center
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PMID: 18418602
responsible party type: Principal Investigator
investigator affiliation: Tri-Service General Hospital
investigator full name: yi-chih HSU
investigator title: Radiologist
mesh term: Carpal Tunnel Syndrome
mesh term: Syndrome
sharing ipd: No
submitted: November 10, 2017
returned: August 15, 2018