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Non-invasive longitudinal study of an MRI biomarker for the quantification of colon inflammation in a mouse model of colitis

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SUPPLEMENTAL DIGITAL CONTENT

Non-invasive longitudinal study of an MRI biomarker for the quantification of colon inflammation in a mouse model of colitis

Andrea Bianchi, PhD; Teresa Bluhmki, BSc.; Tanja Schönberger, PhD; Eric Kaaru, MSc.;

Anne Beltzer, PhD; Ernest Raymond, PhD; Andreas Wunder, PhD; Paresh Thakker, PhD;

Birgit Stierstorfer, PhD; Detlef Stiller, PhD.

Figure S1: (a) MR coronal image showing the slice positioning procedure. Twenty-five consecutive axial slices of the colon (1 mm thickness) were acquired with an interleaved scheme, starting from the anus. The slices were placed perpendicularly to the inserted hollow tube. The positioning procedure of the axial slices was performed in the same way in the sagittal plane. (b) Zoom of colon axial view. (c) Image showing the analysis procedure performed to measure MRI wall thickness (in this case on image (b)). Wall thickness was measured on three different positions of the same axial slice (red solid lines) and was repeated on two different axial slices (roughly 1.2 and 1.8 cm from the anus). The three different points in each slice were selected roughly every 120 degrees. Residual water was easily identified because of its hyperintense MR signal as visible in (c) and was thus excluded from the segmentation process. In (d) the typical ex vivo measurement of the colon wall thickness on histological HE-stained slices is shown (see double arrow in the inset). The procedure was repeated on three positions for each slice, in a similar way to the MRI wall thickness measurement (only one position is shown in the figure as example).

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Figure S2: Intra- and inter-observer reproducibility study for the colon wall thickness measured with MRI (data from all the three time points). Correlation over time (intra- observer) (a) and across observers (inter-observer) (c) of the MRI wall thickness measurements. The diagonal lines correspond to the lines of equality. The 95% confidence intervals are shown as well. Bland–Altman plots showing the means of the measurements over time (b) or across observers (d) against their differences. Dashed lines correspond to the 95% confidence intervals (mean difference ± 1.96 standard deviation). The mean differences (bias) are indicated. r indicates the correlation coefficient.

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Figure S3: Intra- and inter-observer reproducibility study for the colitis score measured with colonoscopy (data from all the three time points). Correlation over time (intra-observer) (a) and across observers (inter-observer) (c) of the colitis score measurements. The diagonal lines correspond to the lines of equality. The 95% confidence intervals are shown as well. Bland–

Altman plots showing the means of the measurements over time (b) or across observers (d) against their differences. Dashed lines correspond to the 95% confidence intervals (mean difference ± 1.96 standard deviation). The mean differences (bias) are indicated. r indicates the correlation coefficient.

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Figure S4: Intra- and inter-observer reproducibility study for the colon wall thickness measured on histological sections (data from the endpoint on day 21). Correlation over time (intra-observer) (a) and across observers (inter-observer) (c) of histology wall thickness measurements. The diagonal lines correspond to the lines of equality. The 95% confidence intervals are shown as well. Bland–Altman plots showing the means of the measurements over time (b) or across observers (d) against their differences. Dashed lines correspond to the 95% confidence intervals (mean difference ± 1.96 standard deviation). The mean differences (bias) are indicated. r indicates the correlation coefficient.

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