Ultrasound Stiffness Imaging in Crohn's Disease
Condition: Crohn's Disease; Ultrasound; Intestinal Fibrosis; Shear Wave Imaging; Acoustic Radiation Force Impulse
MeSH terms: Crohn Disease; Fibrosis
Study type: Observational

Summary: 
      The purpose of this study is to determine whether ultrasound-based assessment of intestinal
      stiffness in patients with Crohn's disease predicts the effectiveness of medical therapy or
      the need for surgical resection.
    

Detailed description: 
      Modern medical therapy in Crohn's disease, including immunomodulators and biologic compounds,
      has revolutionized disease treatment. However, a significant portion of individuals will not
      respond to medications, most often due to the development of intestinal fibrosis. Over the
      course of Crohn's disease repeated episodes of inflammation and abnormal wound healing lead
      to progressive intestinal fibrosis, strictures, and bowel obstruction. While inflammatory
      Crohn's disease often responds to medical therapy, predominantly fibrostenotic intestinal
      disease is unresponsive and requires surgery. Our inability to accurately distinguish
      intestinal inflammation from fibrosis frequently leads to empiric trials of steroids and
      immunosuppressive therapies. This often proves futile, delays inevitable surgery, and
      unnecessarily exposes the patient to medication-related risks for months and sometimes years.
      At present there are no available means to distinguish medically responsive inflammatory
      disease from predominately fibrotic intestinal disease. The unmet need in this field is an
      accurate diagnostic technology to determine which patients will benefit from
      anti-inflammatory therapy, and which patients should go directly to surgery. Non-invasive
      ultrasound stiffness imaging (USI) may be a surrogate marker of underlying bowel wall
      fibrosis that aids in predicting if Crohn's disease will be responsive to medical therapy.

      Two USI methods have recently been developed: Ultrasound elasticity imaging (UEI) uses 2D
      speckle-tracking to measure tissue strain, a surrogate of fibrosis. The second, shear wave
      imaging (SWI), is a commercially available technology that measures the speed of ultrasonic
      shear waves through tissue. Shear waves travel more rapidly through stiff tissue. The central
      hypothesis of this proposal is that ultrasound stiffness imaging (USI) quantitatively
      distinguishes predominately inflammatory from fibrotic bowel wall thickening, and therefore
      is predictive of the likelihood of response to medical therapy or the need for surgery.

      We plan to objectively test our central hypothesis and attain the objective of this
      application by pursuing the following three specific aims:

      Specific Aim 1 (SA-1): Determine if USI stiffness measurements of intestinal strictures in
      Crohn's patients admitted with small bowel obstruction predicts response or failure of
      medical therapy based on CDAI and objective inflammatory biomarkers during index
      hospitalization and at 90 day follow-up.

      Inpatient Inclusion Criteria:

        -  Subjects must be 18 years of age or older

        -  Previous diagnosis of Crohn's disease with imaging demonstrating involvement of the
           ileum

        -  Hospital admission imaging demonstrating small bowel dilation (to > 3.5 cm)

        -  CDAI score of >220.

      Inpatient Exclusion Criteria:

        -  Active Clostridium difficile colitis/enteritis

        -  Presence of abdominal enterocutaneous fistulas in the ultrasound path.

        -  Prior abdominal hernia repair with mesh placement in the ultrasound path.

      Specific Aim 2 (SA-2): Determine if USI stiffness measurements of diseased ileum in Crohn's
      outpatients starting Anti-Tumor Necrosis Factor-Alpha therapy predicts response to medical
      therapy based on CDAI and objective inflammatory biomarkers.

      Outpatient Inclusion Criteria

        -  Crohn's patients age 18 and over starting anti-TNF therapy

        -  CDAI score > 220 to denote clinical disease activity.

      Outpatient Exclusion Criteria:

        -  Active Clostridium difficile colitis/enteritis

        -  Presence of abdominal enterocutaneous fistulas in the ultrasound path

        -  Prior abdominal hernia repair with mesh placement in the ultrasound path

        -  Current use of prednisone or budesonide

        -  Changing anti-TNF due to allergy (including a TNF-induced lupus-like arthritis).
    

Intervention name(s): Ultrasound stiffness imaging
Intervention type(s): Procedure
Intervention description(s): Subjects will undergo transabdominal ultrasound of the distal intestine. Distal intestine motion capture will be used for off-line stiffness assessment by two-dimensional speckle tracking. In addition, shear wave imaging will be used for real-time stiffness assessment.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adult patients with Crohn's disease, either:

          -  hospitalized for small bowel obstruction, OR,

          -  undergoing outpatient start of anti-tumor necrosis factor alpha
      
Keywords: crohn's disease; ultrasound; intestinal fibrosis; shear wave imaging; acoustic radiation force impulse