Introduction 1 3 4 5 7 8 9 9 10 Materials and methods Full ethical committee approval was obtained, and all subjects gave written informed consent. 1 Fig. 1 single star double stars  11 Study power The study was powered to detect a 20% difference in tagging quality (see below) across the four regimens. Based on pilot data, the interclass correlation coefficient between colonic segments was calculated to be 0.30, and it was calculated that a sample size of 22 per group was required (alpha 0.05 at 80% power). CT colonography 2 12 n n One of three experienced radiologists (each with experience of at least 300 CTC cases with endoscopic validation) evaluated the datasets immediately after the examination using a dedicated workstation with proprietary software (Vitrea 3.8, Vital Images, Minnetonka, MN, USA), and noted the segmental location of any polyps or cancers on a study report sheet, together with lesion size measured using electronic callipers applied to the 2D MPR best showing the maximum diameter. The choice of reporting radiologist for each patient was dependent upon the particular recruiting institution and availability on the day of the scan. All three radiologists used a primary 2D approach with 3D reserved for problem solving. Colonoscopy 13 14 Polyp correlation Polyps found at CTC were deemed true positive if a corresponding polyp was found in the same or adjacent segment at endoscopy and if the estimated size of the polyp was within 50% of the endoscopic measurement. Patient experience 15 1 16 Table 1 Bowel-tolerance questionnaire questions and responses in comparison to historical controls undergoing full bowel preparation Variable Response a n b n  P How did you find understanding prep sheet? Easy 56 (63) 48 (70) 0.39 Fairly easy/difficult 33 (37) 21 (30) How did you find swallowing medicine? Easy 43 (48) 44 (64) 0.36 Fairly easy 36 (40) 32 (32) Quite difficult/difficult 10 (11) 3 (4) How did you find coping with special diet? No problem 59 (66) 42 (61) 0.49 Bit difficult 24 (27) 24 (35) Very difficult 6 (7) 3 (4) How did you feel after medicine? Fine 65 (73) 48 (70) 0.96 Unwell/very unwell 24 (27) 21 (30) Did you have any abdominal pain? None 31 (36) 25 (36) 0.37 Mild 39 (45) 27 (39) Moderate/severe 16 (19) 17 (25) Did you have any nausea/vomiting? None 58 (67) 46 (67) 0.92 Mild 22 (26) 18 (26) Moderate/severe 6 (7) 5 (7) Did you experience any faintness or dizziness? None 70 (81) 54 (78) 0.63 Mild/moderate/severe 16 (29) 15 (22) Did you experience any wind? None 25 (29) 26 (38) 0.27 Mild 41 (48) 32 (46) Moderate/severe 20 (23) 11 (16) Did you experience any soreness? None 37 (43) 24 (35) 0.15 Mild 37 (43) 29 (42) Moderate/severe 12 (14) 16 (23) Did you experience any incontinence? None 68 (80) 49 (71) 0.2 Mild 8 (9) 13 (19) Moderate/severe 9 (11) 7 (10) Did you experience any sleep disturbance? None 33 (39) 41 (59) 0.01 Mild 29 (34) 20 (29) Moderate/severe 23 (27) 8 (12) How many times did you open your bowel after starting the preparation? 1–3 1 (1) N/A  3–5 20 (22)   >5 69 (77)   N/A a b 2 Table 2 Questions and responses to follow-up questionnaire pertaining to patient tolerance and preferences Variable Response Patient number (%) How did you find taking the low-residue diet? No problem 46 (67%) Moderately inconvenient 20 (29%) Very inconvenient 3 (4%) How did you find drinking the tagging liquid? No problem 57 (83%) Moderately inconvenient 11 (16%) Very inconvenient 1 (1%) How did you tolerate the preparation before CT? Well 37 (53%) Fairly well 29 (42%) Poorly 3 (4%) How did you tolerate the additional preparation prior to colonoscopy, compared to that before the CT? No problem 51 (74%) More uncomfortable 12 (17%) Much worse 6 (9%) How did you find the preparation before CTC compared to the full colonoscopy preparation? Much better 18 (26%) Better 24 (35%) No better 26 (38%) Grading of bowel preparation 17 Grading of residual stool (irrespective of tagging status) was based on the percentage of total mucosal circumference coated on an axial image. For each colonic segment, the slice with the most residual stool was used to assign the score. Scores were as follows: 1: no residue or scattered residue, 2: coating of <25% or thin circumferential “film” less than 2 mm in depth, 3: coating of ≥25 to 50%, 4: >50% coating. Grading of residual fluid (irrespective of tagging status) was based on the maximum anteroposterior (AP) diameter of the colonic lumen submerged. For each colonic segment, the slice with the most residual fluid was used to assign the score. Scores were as follows: 1: no fluid, 2: <25% AP diameter, 3: ≥25 to 50% AP diameter, 4: >50% AP diameter. 9 2 2 Fig. 2 arrow  Statistical analysis Preliminary data analysis revealed skewed data for most bowel preparation and tagging variables, and thus scores were combined for subsequent analysis. For residue, scores were grouped into either a score of 1, or a score of 2 or more. For residual fluid, scores were grouped into scores of 1/2, or scores of 3/4. Scores for solid residue tagging were grouped into those of ≤4 or 5. Fluid tagging scores were grouped into scores of 1/2, or score of 3. Logistic regression was then applied, adjusting for colonic segment, to compare the four regimens overall, and to compare the distal (rectum, sigmoid, descending) and proximal colon (transverse, ascending and caecum). In addition, the prevalence of layering within tagged fluid was compared on a per-patient basis using the chi-squared test. Tagged fluid attenuation was compared using linear regression following log transformation of the data. Confidence scores for excluding a polyp ≥6 mm were grouped as either <100% or 100%, and compared using logistic regression. For all regression analyses, robust standard errors were employed to account for interdependency between colonic segments and scan position (supine/prone) in the same patient. Results were expressed as the odds of the outcome under consideration compared to regimen A. Questionnaire responses were compared using Fischer’s exact test. Overall categorical per-polyp and per-patient data are presented using descriptive statistics. Given the relatively low polyp incidence (and thus low statistical power), comparative statistics for polyp detection were not performed across regimens. False-positive numbers were compared using one-way ANOVA. Results A total of 95 patients were recruited (50 female, mean age 64 years, range 50–85 years), with 24, 25, 24 and 22 randomised to regimens A to D respectively. Seventy-seven, 13 and 5 patients were recruited from institutions 1, 2 and 3 respectively. Overall, 67 (71%) had a change in bowel habit, 18 (19%) had rectal bleeding, 7 (7%) had non-specific weight loss, and 3 (3%) had a clinically palpable abdominal mass. Bowel preparation P P P Tagging quality 3 P 3 Fig. 3 arrow arrowhead  Table 3 Efficacy of tagging of solid residue according to size and regimen Solid residue size Colon segments Regimen Mean tagging score (SD) a P ≤5 mm All segments A 4.3 (1.2) 1  B 4.3 (1.2) 0.94 (0.39, 2.32)  C 4.5 (1.1) 1.47 (0.56, 3.87)  D 4.5 (1.2) 1.67 (0.68, 4.14) 0.56 b A  1  B  0.97 (0.37, 2.52)  C  0.76 (0.26, 2.27)  D  1.00 (0.38, 2.61) 0.97 c A  1  B  0.85 (0.26, 2.80)  C  4.06 (0.74, 22.1)  D  3.22 (0.95, 10.9) 0.08 ≥6 mm All segments A 4.1 (1.6) 1  B 4.3 (1.5) 1.82 (0.44, 7.62)  C 4.1 (1.7) 1.56 (0.32, 7.76)  D 3.7 (1.8) 0.43 (0.11, 1.65) 0.24 b A  1  B  1.30 (0.26, 2.52)  C  3.84 (0.37, 39.2)  D  0.17 (0.02, 1.27) 0.12 c A  1  B  3.22 (0.26, 39.8)  C  0.94 (0.11, 7.87)  D  0.91 (0.11, 7.54) 0.78 SD a b c P 4 Fig. 4 arrow  P 2 Fluid tagging density P P Patient experience 1 16 P Follow-up questionnaire 2 Diagnostic performance Five patients (one each from regimens A, B, and C and two from regimen D) were excluded from the performance analysis due to a new diagnosis of inflammatory bowel disease (all presenting with rectal bleeding). A further patient (from regimen B) was excluded after refusing colonoscopy. Of the remaining 89 patients, 68 had either normal colonoscopy or diminutive polyps (≤5 mm) only, and 21 had at least one polyp ≥6 mm or cancer. Colonoscopy was incomplete in 10/89 (11%) reaching the transverse colon in 6, sigmoid in 3 and hepatic flexure in 1. Reasons for failure were obstructing stricture (1), severe diverticulosis (1), tortuous colon (5), and pain (3). Only those segments visualised at colonoscopy were included in the assessment of diagnostic performance. Per polyp analysis In total there were 9 polyps ≥10 mm (all adenomatous), 12 polyps 6–9 mm (10 adenomatous, 2 hyperplastic) and 72 polyps ≤5 mm (46 were recovered for histology, of which 26 were adenomatous, 15 hyperplastic and 5 normal mucosa). One 6-mm polyp and two 5-mm polyps were found only on re-look endoscopy after segmental unblinding of the CTC report. No CTC-detected polyps were classified as false positives due to segmental or size mismatching with colonoscopy. 5 4 6 7 P Fig. 5 arrow arrowheads  Table 4 Polyp detection overall and according to tagging regimen Regimen Patient number n n n n n n n P a A 23 2/2 (100%) 1/2 (50%) N/A 3/10 (30%) 0 1 7 0.15 B 23 N/A 3/3 (100%) 5/6 (83%) 10/30 (33%) 0 b 9  C 23 N/A 1/1 (100%) 2/2 (100%) 6/20 (30%) 0 0 1  D 20 N/A 3/3 (100%) 2/4 (50%) 4/12 (33%) c 1 2  Overall 89 2/2 (100%) 8/9 (89%) 9/12 (75%) 23/72 (32%) 1 3 19  N/A a b c Fig. 6 A 54-year-old male with change in bowel habit. Axial CT colonographic image of a 6-mm filling defect in the rectum reported as a polyp. No lesion was found at colonoscopy with segmental unblinding suggesting the lesion was untagged faecal residue  Fig. 7 n  Per patient analysis 5 Table 5 Per-patient performance overall and according to tagging regimen Regimen Patient number n n   Sensitivity Specificity PPV NPV Sensitivity Specificity PPV NPV A 23 3/4 (75%) [33–100%] 18/19 (95%) [85–100%] 0.75 0.95 3/4 (75%) [33–100%] 19/19 (100%) [100–100%] 1.0 0.95 B 23 7/7 (100%) [100–100%] 16/16 (100%) [100–100%] 1.0 1.0 3/3 (100%) [100–100%] 20/20 (100%) [100–100%] 1.0 1.0 C 23 3/3 (100%) [100–100%] 20/20 (100%) [100–100%] 1.0 1.0 1/1 (100%) [100–100%] 22/22 (100%) [100–100%] 1.0 1.0 D 20 5/7 (71%) [38–100%] 12/13 (93%) [78–100%] 0.83 0.86 3/3 (100%) [100–100%] 17/17 (100%) [100–100%] 1.0 1.0 Overall 89 18/21 (96%) [93–100%] 66/68 (97%) [93–100%] a 0.96 10/11 (91%) [74–100%] 78/78 (100%) [100–100%] b 0.99 NPV  PPV a b Reader confidence P Discussion 6 8 10 9 18 1 2 9 10 19 10 20 21 22 5 5 6 23 In conclusion, a combination of reduced laxatives and a simple tagging regimen based on 40% barium sulphate the day prior to CTC maintains acceptable diagnostic accuracy. Three doses of 20 ml 40%w/v barium sulphate are as effective as more complex regimens, but fluid tagging can be manipulated by addition of dilute barium or meglumine amidotrizoate on the morning of CTC, the latter also reducing the volume of residual stool.