Comparison of Standard and Low Dose CT Enterography for Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Study type: Observational

Summary: 
      The investigators will be assessing the efficacy of a Model Based Iterative Reconstruction
      algorithm (MBIR) as a noise reduction tool in computed tomographic (CT) examinations for
      Crohn's Disease. MBIR is computer adapted mathematical calculation technique that generates
      CT images with less picture degradation (noise) than traditional computer reconstruction
      techniques such as FBP (Filtered Back Projection) and ASIR (Adaptive Statistical Iterative
      Reconstruction), for enteric Crohn's Disease findings.

      The research involves collection of data from subjects standard of care diagnostic CT scan
      and from a research low radiation dose scan performed immediately following their diagnostic
      scan. We will determine the impact on image quality, interpretability, and Crohn's Disease
      findings of the low dose scan compared to the standard of care scan.

      FBP, MBIR, and ASIR are post processing tools that do not alter the scan acquisition itself.
    

Detailed description: 
      1. PURPOSE

           The purpose of this study is to assess the efficacy of a new model based iterative
           reconstruction algorithm as a noise reduction tool and to compare its sensitivity for
           the findings of enteric Crohn's Disease with the sensitivity of FBP or ASIR CT
           Enterography findings in enteric Crohn's Disease.

           Definitions:

           Iterative reconstruction: A computer adapted mathematical calculation technique that
           allows the ability to generate CT images with less image noise (picture degradation)
           than traditional image reconstruction techniques.

           Reconstruction algorithms are computer adapted mathematical calculations applied to raw
           data during image reconstruction.

        2. HYPOTHESIS

           The use of different CT reconstruction algorithms will allow the quantitative assessment
           of small bowel Crohn's Disease (CD) while exposing patients to lower radiation doses.
           MBIR and ASIR will provide images with lower noise and similarly accurate quantification
           of CD. Additionally, MBIR will allow acquisition of CT data at very low radiation doses,
           with comparable image quality and quantitative assessment of CD compared to higher
           radiation dose acquisitions performed utilizing FBP and ASIR. MBIR will not be inferior
           to FBP or ASIR in assessing findings related to Crohn's Disease on CT enterography
           (CTE).

           Definitions

           MBIR: Model Based Iterative Reconstruction algorithm FBP: Filtered Back Projection ASIR:
           Adaptive Statistical Iterative Reconstruction

        3. JUSTIFICATION

           Computed tomography imaging traditionally relied upon filtered back projection (FBP) for
           image reconstruction. This technique uses relatively little computing power, but
           requires a number of assumptions be made about the data acquisition itself that result
           in an increase in image noise.

           The use of iterative reconstruction techniques has recently started to take place in CT
           imaging. The major benefit of iterative reconstruction techniques is the ability to
           generate CT images with less image noise. This noise reduction allows for tube current
           reduction with IR images, limiting radiation dose in a linear manner.

           Model based iterative reconstruction (MBIR), is replacing the older iterative technique,
           adaptive statistical iterative reconstruction (ASIR). MBIR utilizes more accurate
           modeling and early research suggests MBIR images may be reconstructed from CT
           acquisitions that use significantly decreased radiation dose, with similar image quality
           compared to both ASIR and FBP.

           FBP, MBIR, and ASIR are post processing tools that do not alter the scan acquisition
           itself. Iterative reconstruction algorithms have garnered increased interest, especially
           with elevated public concern about radiation dose . MBIR techniques have not yet been
           validated in CT examinations acquired for evaluation of Crohn's Disease (CD).

           Clinical history, physical examination, laboratory investigations and endoscopy have
           been used to identify and evaluate the extent and severity of Crohn's Disease along with
           imaging studies to assist in the evaluation of the small bowel involvement of CD. CT
           Enterography has become the preferred imaging modality for assessing small bowel
           involvement in inflammatory bowel disease. The dose reduction properties of MBIR are
           particularly appealing in this area of CT imaging as multiple scans may be performed
           over time to assess progression or relapse of disease and response to treatment.

           Calprotectin is a protein found inside the cytoplasm of the immune cells within the
           intestine known as neutrophils, granulocytes and macrophages. Under conditions of
           mucosal inflammation as seen in inflammatory bowel disease, calprotectin is released
           into the lumen of the bowel and excreted in the stool. Fecal Calprotectin levels can be
           measured and serve as a biological marker of the degree of mucosal inflammation in the
           bowel. Fecal calprotectin levels have not been previously correlated with the degree of
           mucosal inflammation seen on CT Enterography.

        4. OBJECTIVE

           To determine the impact on image quality, interpretability, and Crohn's Disease findings
           of low dose computed tomography enterography (CTE) images acquired with a new model
           based iterative reconstruction algorithm as compared to standard image reconstruction.

        5. RESEARCH METHOD

           The research is a prospective non randomized study of 163 consecutive patients who are
           clinically referred for CT Enterography.

        6. STATISTICAL ANALYSIS

      Using sensitivity of the CTE to calculate sample size, the planned sample size for this study
      is 163 subjects. The study will be powered at 80% to demonstrate that the lower radiation CTE
      (ASIR and MBIR) is non-inferior (type I error rate of 2.5%, one sided) to the standard CTE.
      The sensitivity of the standard CTE is assumed to be 0.77 based on a pooled estimate [7]. 0.1
      is chosen as the non-inferiority margin. The correlation between the two procedures is
      considered in the sample size calculation. We assume that the prevalence of Crohn's Disease
      is 80% among the target population.

      Using the nQuery statistical program, with the assumption that the proportion of discordant
      examinations is 0.15(or the conditional probability of positive finding in standard CTE is
      0.90 if given a positive finding on the ASIR or MBIR CTE), the sample size needed to detect
      no more than 0.1 difference in sensitivity of the two procedures for patients with disease is
      118, with a 80% power and a type I error of 0.025, one sided. Assuming that 80% of target
      population will have disease, approximately 148 subjects will need to be recruited. We have
      factored in a 10% drop out rate ( patients who leave the study for any reason) bringing the
      total number of patients to be recruited to 163.

      Image quality scores and quantitative analysis will be compared using both standard and the
      novel reconstruction algorithms. These results will also be compared to the acquired FC
      levels. Because each patient examination will receive multiple reconstructions, a mixed-model
      analysis will be conducted to account for repeated observations within patients. Repeated
      measures analysis of variance will be conducted separately for each outcome (signal, noise,
      SNR, proportion of interpretable segments, and image quality) against the type of
      reconstruction used. A 0.05 significance level will be used for all repeated measures and
      analysis.

      Primary Endpoint:

      FBP, ASIR and MBIR will each be compared to the reference standard described below. The
      endpoint will be the ability of each method to accurately identify the presence or absence of
      Crohn's Disease (CD) as compared to the reference standard.

      Reference Standard:

      Dr. B. Bressler, the principal investigator, is a gastroenterologist with an expertise in
      inflammatory bowel disease (IBD). Dr. Bressler will review all of the available clinical
      parameters including history and physical exam findings, ileocolonoscopy findings if
      available and laboratory parameters including bloodwork and Fecal Calprotectin levels. The
      gastroenterologist will not be blinded to the subject's identity. Based on his review of the
      above parameters, he will rate the presence of small bowel CD as definitely active, probably
      active, inactive (remission) or absent.
    

Intervention name(s): CT Enterography
Intervention type(s): Radiation
Intervention description(s): Diagnostic CT Enterography Scan (CTE)
Subjects will have their scheduled diagnostic CTE scan done according to St. Paul's Hospital radiology department standard procedures. Subjects will be randomly assigned to undergo a low dose CT Enterography scan either before or after the diagnostic scan. The radiologists who are blinded to the technique used will then interpret the scans to look for signs of Crohn's disease. The low dose scan will be compared to the standard scan in terms of it's ability to detect signs of Crohn's disease.
Other intervention name(s): CT Scan to include imaging of the small bowel and colon
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients suspected of having Crohn's Disease who are referred for CT Enterography
        examination by their gastroenterologist
      
Keywords: CT Enterography; Crohn's Disease; Inflammatory Bowel Disease