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Research Advances - Overview

Since 1997, our group of Radiologists and Gastroenterologists have collaborated intensively to advance the field of CT colonography, also known as virtual colonoscopy (43, 45, 49, 50, 57, 62-71). This research has focused on improving patient preparation, data acquisition, and data interpretation techniques. Key developments are listed below:

Technical Developments and Data Acquisition

1. Low dose technique. Colorectal neoplasms (tumors): Prospective comparison of thin-section low-dose multi-detector row CT colonography to conventional colonoscopy for detection (50). Determined that CT colonography could be performed using a low radiation dose and yet maintain high sensitivity for clinically significant colorectal polyps.

2. Utilization of thin slice collimation (cross-sectional image). Effect of different slice thickness on CT colonography data interpretation: Preliminary observations (67). Showed that the false positive rate with CT colonography was decreased by using 1-mm-thick CT collimation as opposed to 5-mm-thick slices.

3. Bowel preparation. Effect of different bowel preparations on residual fluid at CT colonography (57). Showed that large amounts of residual fluid in the colon are more likely to be present when poly-ethylene-glycol preparations are used than when phospho-soda preparations are used.

Clinical Implementation

1. Failed colonoscopy. CT colonography in patients with failed colonoscopy (62). Showed that CT colonography could be performed in patients after an incomplete colonoscopy and that lesions near the areas examined during the colonoscopy could be identified.

2. Screening. CT colonography for the evaluation of colorectal polyps and cancers in asymptomatic average risk patients (69). Evaluated the accuracy of CT colonography in the detection of clinically significant colorectal lesions in patients with no symptoms.

3. What is a clinically significant colorectal polyp? Clinical significance of missed polyps at CT colonography (10). Developed an algorithm to determine appropriate follow-up screening and surveillance intervals based on the results of CT colonography interpretation.

Data Analysis

1. Interpretation. Utilization of two-dimensional and three-dimensional images to differentiate lesions in the colon (45, 65). Demonstrated how 2D and 3D images are necessary and complimentary when interpreting CT colonography data.

2. Data interpretation. Comparison of time-efficient CT colonography with two-dimensional and three-dimensional colonic evaluation for detecting colorectal polyps (43). Showed that CT colonography could be interpreted in a time-efficient manner (less than 15 minutes per case without sacrificing accuracy), thus increasing the clinical usefulness of the examination.

CT Colonography Using Conventional Bowel Preparation

We have studies of over 350 patients (symptomatic and asymptomatic) with CT colonography performed immediately prior to conventional colonoscopy. All of these subjects underwent complete bowel cleansing, with either two 45-ml doses of phospho-soda (the evening before and the morning of the examination) or four liters of polyethylene-glycol. Direct comparison of CT colonography and colonoscopy shows that with thin-section CT colonography and after bowel cleansing the structural appearance and detection rates of clinically significant colorectal lesions is similar.

Technical Developments

The radiation dose delivered to the patient during CT scanning is an important concern, especially if CT colonography is to be used for screening purposes. There are a number of techniques that can be used to reduce the radiation dose, include increasing slice thickness and pitch or lowering the tube current or kVp. The problem with increasing slice thickness is that thick-section images have been shown to be less accurate than thin-section multi-detector row images. Compared to single slice CT colonography, multi-detector row CT colonography increases the radiation dose to patients. This is primarily related to a penumbra effect of radiation that is administered to the patient but not used for data acquisition (50). To compensate for this effect, while still using the more accurate multi-detector row technique, we manipulated the tube current (mAs) used to obtain the image. Tube current is directly proportional to the radiation dose received by the patient. We showed that clinically significant colorectal polyps could be detected with multi-detector row CT colonography using a much lower mAs than was previous used, and hence a much lower amount of radiation. This is possible because of the inherent highly visible contrast between the gas pumped into the colon for the procedure and the colon wall. By lowering the mAs the dose is proportionally decreased, while the sensitivity for detecting clinically significant colorectal polyps is maintained (See Figure 1).


Figure 1. Comparison of CT colonography and conventional colonoscopy in colorectal polyp detection in 161 patients using a low dose technique

Data Acquisition

There has been controversy regarding what slice collimation to use to optimize CT colonography (42). We showed that thin section CT colonography (1 mm), when compared with thicker sections (5 mm), decreased the number of false positive findings with CT colonography (67). The near isotropic voxels (volume elements, the basic units of CT reconstruction) available for data review with thin section technique allows less volume averaging and better evaluation of multi-planar reformatted and 3D views of the inside of the colon. This allows the Radiologist to better differentiate among fecal material, folds between the sacs of the colon, and true polyps. The importance of this is that by decreasing the number of false positive findings with CT colonography, the number of unnecessary colonoscopies can be decreased. This should be further improved with a 16 row detector CT scanner which uses .75 mm thick sections. Our current study design uses a 16 row scanner.

Bowel Preparation

From our initial evaluations of CT colonography after incomplete colonoscopy, we realized that polyethylene-glycol preparations leave large amounts of residual fluid in the bowel. This is not a problem at colonoscopy, since fluid can be washed away or aspirated from the colonic cavity with the endoscope. However, CT colonography examinations are limited to just two projections and large amounts of fluid can obscure the colonic surface, limiting the ability to detect polyps. We showed that the use of a phospho-soda preparation leaves significantly less fluid when compared with polyethylene glycol preparations, thus increasing the likelihood that a lesion will be detected (57). Currently, most CT colonography is performed with a phospho-soda preparation unless there is a contraindication such as renal or cardiac failure.

Clinical Implementation

Incomplete colonoscopy

In 1997, our initial work in the evaluation of CT colonography was to determine how it could be used clinically. Over a period of a year, 20 patients underwent CT colonography immediately after an incomplete colonoscopy. In this study, two clinically significant colorectal lesions were identified in the upper section of the colon (62). These lesions were subsequently confirmed with a follow-up colonoscopy.

There are several reasons why virtual colonoscopy makes for a good follow-up study after an incomplete colonoscopy. Using CT colonography immediately after a colonoscopy takes advantage of a single bowel preparation. Moreover, the colon is usually well distended from the prior colonoscopy and only minimal amounts of additional gas are required. Traditionally, double contrast barium enema (DCBE) has been used as a follow-up exam to an incomplete colonoscopy, but the air that remains in the colon after the colonoscopy can block the barium from coating the entire colon and providing a full view. This limitation does not exist with CT colonography. Because of these advantages, at NYU and in many centers, the procedure of choice by Gastroenterologists in evaluating the upper colon after incomplete colonoscopy is CT colonography.

Screening

A criticism of many studies evaluating CT colonography is that most have focused either on populations of patients with colorectal symptoms or patients in high risk categories (42). We have evaluated CT and conventional colonoscopy in the detection of polyps in asymptomatic average risk patients (69). Sixty asymptomatic male patients over 50 years of age who were referred for screening colonoscopy were enrolled. Sixty-eight polyps were identified by colonoscopy in 36 patients (Figure 2). The sensitivity of CT colonography was 11.5% (9/78) for polyps 1-5mm; 52.9% (9/17) for polyps 6-9mm; and 100% (3/3) for polyps ³ 10mm. Twenty-four patients (45.8%) had a normal colonoscopy. Virtual colonoscopy correctly identified 21 of 24 (87.5%) as normal. These results are similar to our larger studies evaluating patients with and without symptoms. This preliminary work suggests that CT colonography may be an accurate method for detecting clinically significant colorectal lesions in a screening population. Importantly, the mean interpretation time in this group of patients was 9 minutes. Interpretation times in this range are important if CT colonography will ever be used as a widespread screening tool. Moreover, these results are similar to a recently published paper in which 1,233 asymptomatic patients were studied (44).


Figure 2. Stratification of polyp detection rate with virtual colonoscopy based on polyp size.

Significance of Colorectal Polyps

A major concern of all techniques that evaluate the colon is their ability to detect clinically significant polyps. Size has been shown to be the most simple and practical indicator of polyp pathology and is closely related to the degree of abnormality within the lesion (2). The significance of the diminutive (= 5mm) polyp is controversial (5, 72, 73). Most diminutive colorectal polyps are either hyperplastic polyps (growths representing an increase in cellular tissue) or small tubular adenomas (usually benign glandular tumors). While most cases of colorectal cancer develop from adenomas, the vast majority of diminutive adenomas never progress through the complete sequence of genetic alterations that lead to carcinoma, and of those that do, the dwell time is long (1, 9). An endoscopic surveillance study of small colorectal polyps has shown that many remain stable or actually regress over time (72). As a result, it has been suggested that attention should be shifted away from identifying and removing all diminutive polyps and toward colorectal screening strategies that will allow reliable detection of the less common, but more dangerous, clinically significant advanced adenomas (5, 10).

Our own experience with CT colonography in the detection of colorectal polyps has shown that the sensitivity is directly related to polyp size (10, 50). Between July 2001 and March 2003, 186 patients were enrolled in a study at NYU to determine polyp detection rates based on size (Figure 3).


Figure 3. Stratification of polyp detection rate with virtual colonoscopy based on polyp size. *Note 19 of the 22 polyps measuring > 10 mm

While colonoscopy is considered the gold standard in polyp detection it is an imperfect test. In our study there were a total of 28 lesions detected at CT colonography that were not matched according to size, location or morphology (structure) with findings at conventional colonoscopy. Therefore, these 28 lesions were considered “false positives.” Seventeen (60.7%) were = 5 mm, 8 (28.6%) measured 6-9 mm, and 3 (10.7%) were = 10 mm. The three lesions = 10 mm seen at CT colonography that were not detected at colonoscopy showed homogeneous attenuation and morphologic characteristics that were consistent with polyps. All three of these subjects underwent repeat colonoscopy which confirmed the presence of a colorectal polyp at the expected location as demonstrated by CT colonography (10). Therefore, as shown in this study, CT colonography after bowel cleansing did not detect most diminutive polyps, the majority of which were not significant (70% being hyperplastic polyps or normal colonic mucous membrane). CT colonography performs similar to colonoscopy in detecting larger clinically significant lesions.

Data Interpretation

In order for CT colonography to have an impact on colorectal screening it will need to be interpreted in a time-efficient manner. We showed that detection of clinically significant colorectal polyps is similar using a primary 2D approach with 3D imaging for problem solving only, as compared to complete evaluation with 2D and 3D imaging (43). This allows for interpretation times of approximately 10-12 minutes per examination. However, with the use of thin section CT colonography and improved 3D rendering capabilities of workstations, the possibility of using a primary 3D approach is being re-evaluated (44). As technology improves and capabilities for examining endoluminal (interior) areas become faster, the possibility of 3D imaging as a primary imaging technique will need to be reevaluated. Our initial experience with fecal segmentation shows that several artifacts related to the segmentation process will need to be overcome before 3D imaging can be used for CT colonography without bowel preparation. In any case, knowledge of the appearance and pitfalls of using 2D and 3D imaging need to be understood to optimize data interpretation.

An additional benefit of virtual colonoscopy is that it can reveal anomalies outside the colon. During the virtual colonoscopy procedure, the entire abdomen and pelvis is evaluated for incidental abnormalities including aortic aneurysms, renal and adrenal masses, and abnormal enlargement of the lymph nodes. A previous study showed that significant abnormalities outside of the intestines may be identified using CT colonography (77). Our own evaluation showed that of 250 patients undergoing CT colonography at NYU, 33% had one or more extra-colonic findings. Of the 136 total findings, 12.5% were considered highly significant (by the Gastroenterologist), including lung and renal masses. In 4.4% of patients, extra-colonic findings led to further testing and to a change in patient management.

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