Introduction 1 6 7 12 13 15 7 The purpose of this study was to evaluate limited bowel-preparation CTC using an oral contrast agent (amidotrizoic acid) in terms of image quality, patient acceptance and polyp visualization using conventional colonoscopy (CC) as a reference standard. A second objective was to determine the effect of substantially reducing the radiation dose levels on the diagnostic accuracy of limited bowel preparation CTC, again using CC as the reference standard. Materials and methods Study population 16 CTC bowel preparation and scanning protocol 2 Colonoscopy 17 Simulation of low-dose CT colonography 18 19 13 14 13 CTC evaluation 1 Table 1 Scales used by observer 1 to rate image quality (upper part) and scales used by the patients to rate experience and preference Observer 1: Scale Image quality (patient, segment)* 1: poor, not diagnostic; 2: moderate, diagnostic with limitations; 3: good, diagnostic with minor limitations; 4: excellent, no limitations Distension (segment) 1: collapsed; 2: poorly distended; 3: only moderately distended but segment is distended over its full length; 4: good; 5: very good Homogeneity (segment) 1: poor; 2: moderate; 3: good; 4: very good Presence of stool (segmemt) 1: large amount of stool, segment fully filled; 2: moderate amount of stool, ~50% of lumen filled; 3: small amount of stool; 4: only contrast layer on the wall; 5: no stool at all Patients:  Most burdensome aspect CTC preparation: diet, lactulose, contrast agent  CTC: iv puncture, catheter placing, insufflation, breathholds, prone position  CC: iv puncture, moving of scope, air insufflation, monitoring after CC How burdensome/painful Not, mild, moderate, severe, extreme Preference Definitely CTC, probably CTC, possibly CTC, indifferent, possibly CC, probably CC, definitely CC Most reluctant factor CC, bowel preparation prior to the CC, CTC, the limited bowel preparation prior to the CTC *The items were scored per patient and per segment. Polyp detection and image quality A polyp detected at CTC was labeled as true positive if three criteria were met: segmental location and location within the segment corresponded with CC (when situated near the borders of the segment, localization in the adjacent segment was also accepted), the polyp size as estimated by the endoscopist (open forceps) corresponded with size as measured on CTC (50% margin based on the CC size was allowed), and appearance (morphology) closely resembled that of the corresponding polyp at videotaped CC. The unblinded research fellow determined the nature of false-positive findings ≥10 mm by reviewing the videotaped CC and CTC. If the polyp was possibly missed at CC, a repeat CC was called for. Patient questionnaires 1 Statistical analysis P Results 2 Table 2 Baseline characteristics of the study population Included 61 Male/female 40/21 † 61 ± 12 (27–81) Indication:  † 38 H/O colorectal carcinoma 9 † 14 Coexistent complains: Abdominal pain/hematochezia/altered bowel habits 12/4/3 Colonoscopy: number of polyps/patients with polyps:  Any size 94/38 ≥6 mm 28/20 ≥10 mm 15/12 ≥10 mm initial colonoscopy 13/11 Morphology of polyps ≥6 mm (sessile/stalked/flat/CRC) 12/7/7/2 Morphology of polyps ≥10 mm (sessile/stalked/flat/CRC) 3/6/4/2 Colonoscopy: no. of patients receiving Sed+analg/sed/analg/none 29/7/3/22 Stool consistency prior to CTC (diarrhea/soft/normal) 15/13/33 Abdominal pain prior to CTC (major/minor) 1/7 Flatulence prior to CTC (major/minor) 3/27 Spasmolitycs during CTC (Buscopan/Glucagon/neither) 47/12/2 † In five patients it was not possible to fully inspect the colon endoscopically. In one patient a 14-mm polyp was seen at CTC in a segment not inspected at CC and confirmed at surgery (not included in the analysis). In two patients, repeat CC showed a 30-mm polyp and a 30-mm carcinoma (included in the analyses), both missed at the initial CC. Image quality 1 Fig. 1 Figure showing RDOR with confidence intervals of all six segments of the colorectum in both prone and supine position regarding overall image quality, distension, presence of stool and homogeneity. All segments are compared to the best segment (DOR by definition 1). Confidence intervals not reaching 1 indicate significantly inferior results  Diagnostic value 2 3 Fig. 2 a b c  Table 3 Performance characteristics per observer per size category Variable Polyps ≥10 mm Polyps ≥6 mm Observer: Observer: 1 2 1 2 Analysis according to polyp     Sensitivity 10/15 (67%) 9/15 (60%) 17/28 (61%) 15/28 (54%) FP 5 8 20 28 PPV 10/16 (63%) 9/17 (53%) 17/38 (45%) 15/43 (35%) Analysis according to patient     Sensitivity 8/12 (67%) 8/12 (67%) 13/20 (65%) 13/20 (65%) Specificity 45/49 (92%) 41/49 (84%) 30/41 (73%) 25/41 (73%) PPV 8/12 (67%) 8/16 (50%) 13/24 (54%) 13/29 (45%) NPV 45/49 (92%) 41/45 (91%) 30/37 (81%) 25/32 (78%) PPV: positive predictive value; NPV: negative predictive value; FP: false positives; CI: confidence interval Polyp detection at lower dose-levels 4 3 4 Table 4 Performance characteristics of observer 3 per dose level Variable Polyps ≥10 mm Polyps ≥6 mm Dose level Dose level Original 2.3 mSv 0.7 mSv Original 2.3 mSv 0.7 mSv Analysis according to polyp       Sensitivity 5/10 (50%) 7/10 (70%) 4 /10 (40%) 11/20 (55%) 13/20 (65%) 10/20 (50%) FP 2 2 4 5 11 20 Analysis according to patient       Sensitivity 5/9 (56%) 7/9 (78%) 4 /9 (44%) 10/15 (67%) 12/15 (60%) 9/15 (45%) Specificity 40/42 (95%) 40/42 (95%) 39/42 (93%) 33/36 (92%) 26/36 (72%) SS SS P Fig. 3 a b c  Fig. 4 a b c  Patient experience and preference 5 6 P 6 P P 6 P P Fig. 5 Graph showing how patients rated the three different components of CTC with limited bowel preparation. How burdensome were the diet, lactulose and the contrast agent?  Fig. 6 Graphs show patients’ experience of the bowel preparation (upper left) and the CTC examination (upper right) and patient preference for one of the two modalities (CTC with limited bowel preparation versus CTC with standard bowel preparation, lower). How burdensome was the limited bowel preparation prior to CTC (grey) as compared to cleansing prior to CC (black)? How burdensome were the CTC (grey) and CC (black) examinations (upper right graphs)? What did participants prefer for their next examination (lower graph) directly after both examinations and in the questionnaire sent at home 5 weeks later?  Discussion This study demonstrates that CT colonography without cleansing is preferred to colonoscopy and shows moderate sensitivity (60–67%) for polyps ≥10 mm without impaired diagnostic value at mSv levels as low as 0.7 mSv. Image quality was good on average. Nevertheless, the cecum, sigmoid and rectum showed overall reduced image quality. Although this can be caused by the pelvis causing more noise, reduced imaged quality must probably be attributed to inferior homogeneity in the cecum and rectum and inferior distension in the sigmoid and rectum in the prone position. In contrast to the known problems in CTC with distension, which are solved by dual positioning, inferior homogeneity in the cecum and rectum are typical for the limited bowel preparation protocol. Insufficient homogeneity in the cecum is probably caused by the fact that patients ate food after the last amount of contrast agent was taken, resulting in inadequately tagged stool. The inhomogeneous stool in the rectum probably was caused by the fact that in patients with a long transit time stool was already shaped before the fecal tagging was started. We assume that two adaptations are necessary to improve image quality. First, contrast must be taken as long as the patients are eating. Second, stool should be made softer, for example by replacing lactulose by a stronger osmotic laxative (e.g., low-dose magnesium salts), thereby also reducing the transit time and reducing the amount of non-tagged stool in the rectum. Although these adaptations increase the burden of the bowel preparation, they are slight and are required to improve image quality and thereby maybe the sensitivity and specificity. 7 20 21 23 Since two of five (observer 1) and two of six (observer 2) missed polyps were not seen in retrospect by the unblinded observer, the problem of missing large polyps can be regarded as predominantly an interpretation problem rather than a visualization problem. Future developments, such as better homogeneity, better distension, better learning curve, intuitive display modes, electronic cleansing and computer-aided detection can help in reducing the number of missed polyps. 13 24 27 28 29 24 Several potential limitations must be considered. The number of patients included is relatively low, especially for determining the detection parameters at the 2.3 and 0.7 mSv levels. In the current study no segmental unblinding during CC was performed. Although repeat CC showed that two large false-positive lesions were missed at the initial CC, segmental unblinding has the advantage of evaluating all false positives. Since no electronic cleansing was used and many polyps were submerged, 3D evaluation of these lesions was not of additive value. However, 3D evaluation with electronic cleansing might have given better results, especially since most missed polyps were visible in retrospect. 30 31 When filling out the questionnaires, sensitivity for CC and CTC were assumed equal. If patients knew that the sensitivity of CTC was lower than for CC, this most likely would have influenced the preference for CTC negatively. In conclusion, these results show that CTC with the limited bowel preparation protocol used in this study is feasible, even when using doses as low as 0.7 mSv levels. Although sensitivity was not as high as previously reported, this is most likely not due to the limited bowel preparation, but to interpretation problems. Technical developments will probably increase the sensitivity, while minor adjustments in bowel preparation may reduce the number of false positives, especially when using low-dose protocols. Since patient acceptance was very good, this technique can be regarded as promising in screening patients of populations with a low prevalence of polyps.