Low-Dose Unenhanced Computed Tomography with Iterative Reconstruction for Diagnosis of Ureter Stones

Ureter stones are a common health problem in Korea with noted increases in their incidence, prevalence, and recurrence. In general, 50% of patients with recurrence have one recurrent episode, whereas more than 10% have multiple recurrences.1, 2, 3, 4 Recently, unenhanced computed tomography (CT) with a thin section and multi-detector has been increasingly used for renal colic patients because it provides a rapid and accurate examination.5, 6 Furthermore, unenhanced CT has become the new diagnostic gold standard due to its ability to identify other causes of renal colic, as well as its higher sensitivity and specificity for the detection of ureter stones, compared to other modalities, such as intravenous pyelography or ultrasonography.7

With the widespread use of unenhanced CT for the diagnosis of ureter stones, radiation exposure has become a major concern. Although the risk induced by an individual unenhanced CT scan is minute, the lifetime cumulative effect from a large number of exposures might confer a risk for cancer in young ureter stone patients who have multiple recurrences.8 Therefore, the “as low as reasonably achievable” (ALARA) principle is used to achieve the lowest radiation dose possible during unenhanced CT examinations while maintaining optimal image quality.9 Reducing radiation exposure during the evaluation of renal colic is now one of the main focuses in the field of urology, and low-dose unenhanced CT (LDCT) is the most promising option for diagnosing ureter stones. The recently introduced iterative reconstruction (IR) algorithms for CT have shown promise with regards to dose reduction, compared with standard filtered back projection (FBP), and these algorithms were found to reduce image noise in our previous studies using phantom and clinical trials of renal colic patients.10, 11, 12 However, these studies have several limitations. In a phantom study, the phantom has a simple constitution, compared with the human body. In addition, a stone with a fixed size in the hole of a phantom could make the diagnosis of urolithiasis rather simple.11 In previous clinical trials, we repeated CT scans at the same time with different settings (standard dose and low dose).10 This approach can lead to enrolment limits regarding the number of patients, as well as significant ethical issues, although we obtained informed consent and provided a thorough explanation. Herein, we evaluated the efficacy of LDCT with the use of the IR technique (LDCT-IR) for reducing the radiation dose and image noise while maintaining clinical usefulness via a prospective and randomized study.

This prospective study was approved by the Institutional Review Board of Chung-Ang University Hospital [IRB No. C2012234 (1194)], and informed consent was obtained from all patients who were enrolled in this study. We attempted to conduct a prospective, single blind, randomized, and non-inferiority study at a single university hospital.

In our study, the LDCT-IR scan was not inferior to the SDCT scan for the stone detection rate according to the final clinical diagnosis and clinical outcomes, which included the difference in the clinical manifestations of patients. Moreover, LDCT-IR reduced the radiation dose to 75.2%, compared to SDCT. This means that the LDCT-IR scan is useful for evaluation of renal colic patients and for the diagnosis of ureter stones in the ED, with an overall sensitivity and specificity of 93.9% and 100%, respectively.

In our study, we used LDCT-IR to decrease the image noise accompanied by radiation dose reduction. Malkawi, et al.13 reported that LDCT scan (10%) without any post-processing noise reduction techniques was inferior to SDCT scan for the evaluation of renal colic patients, and had an overall sensitivity and specificity of 70% and 39%, respectively. However, Kwon, et al.10 investigated 116 patients with suspicious ureter stones by LDCT-IR, and the mean ED was 1.39 mSv, which showed a 76.6% reduction. The sensitivity and specificity of LDCT-IR were 99.1% and 100%, respectively, and it had a diagnostic accuracy of 100% for stones greater than 3 mm. Park, et al.14 investigated 103 patients by LDCT-IR and observed a mean ED of 0.68 mSv. An accuracy of 100% for ureteral stones more than 3 mm in diameter was achieved with an approximately 91.82% reduction of the radiation dose.

Application of LDCT-IR is suitable for the detection of ureter stones because of its high contrast between almost all ureter stones and the adjacent lower density soft tissue. However, this difference may be inaccurately placing the calcifications on LDCT without IR inside or outside of the ureter, and it is difficult to distinguish ureteral stones and phleboliths with vascular calcifications. This placement error is due to the loss of resolution at the thin ureter, and the reason for this loss is that LDCT is not designed to evaluate soft tissue. This problem would apply to all ureteral stones without ureteral dilatation or hydronephrosis. However, the IR technique is available for low contrast abdominal soft structures, and this technique is thus applicable for distinguishing between ureteral stones and phleboliths.10 Therefore, we believe that the IR technique might be essential for clinically available LDCT.

One patient in the SDCT group was clinically proven as having a ureter stone, although it was documented as phlebolith in our study. This patient did not have ureteral dilatation and hydronephrosis. Although efforts to differentiate a ureter stone from a phlebolith have been made with the “tissue rim” or “comet tail” signs, the tissue rim sign has the disadvantage of size dependency. Smaller ureteral stones are more likely to exhibit a tissue rim sign than are larger calculi.15, 16 According to a study by Heneghan, et al.,17 the soft tissue rim sign was found to have a sensitivity of 77% and specificity of 92%. The comet tail sign has been found to have a sensitivity 21–65% and a specificity of 100%.16, 18 Their presence without ureteral dilatation needs to consider phlebolith, but it is occasionally observed adjacent to calculi.15 From our results, the difficulty of differentiating between ureteral stones and phlebolith is not only evident for LDCT but is also evident for SDCT, so it is very important that an experienced physician reviews the CT scan to overcome this problem.

In our study, unsuspected diseases beyond ureter stones were identified in one patient with acute diverticulitis in the SDCT group. The presence of an alternative diagnosis on standard high dose CT may be as high as 13%, and Poletti, et al.19 reposted the same detection rate of an alternative diagnosis in their series. In terms of an alternative diagnosis, our results are not conclusive. In general, young adults whose presentations mimic renal colic would rarely prove to have serious chronic or malignant disease. Reports indicate that it is feasible to considerably reduce the dose of CT radiation for the diagnosis of appendicitis or diverticulitis, which are important alternative diagnoses.8, 20 For other alternative diagnoses, such as those of a complicated adnexal cyst, pelvic inflammatory disease, or acute pyelonephritis, CT examination may not be critical since the diagnosis in these cases should be based on clinical findings or other types of diagnostic tests.

Our study had a few limitations in that only limited numbers of patients were enrolled, even though the study used a prospective blinded technique. According to sample size calculation in this non-inferiority study, a total of 304 subjects, 152 persons per group, was required. However, it was difficult to recruit patients for our study because they were worried about additional imaging and misdiagnosis from LDCT. Compared with SDCT, LDCT-IR was not inferior in terms of the diagnosis of ureter stones, although these concerns and our study overcame the ethical problem of previous studies in which LDCT and SDCT were simultaneously performed in patients. Additionally, a potential limitation of LDCT is misdiagnosis as mentioned above. There may be other diseases that can cause colicky flank pain, such as ureteropelvic junction obstruction, acute pyelonephritis, urothelial carcinoma, or diseases of gastrointestinal or gynaecological organs, that can be exacerbated by low-dose CT. In the present study, one patient was diagnosed with acute appendicitis. It is clear that a close physical examination and careful inspection of clinical symptoms is necessary. Finally, this study was not designed to evaluate the interobserver variability or effect of having the studies read by urologists instead of radiologists. The reason for the design of this study was that the interobserver agreement was consistently excellent (0.907–1.000) when the analysis was categorized by the size and location of the ureter stones, which was shown in our previous study.10 The interpretation of LDCT-IR by urologists was reliable and not inferior to that by radiologists. Overall, our results indicate that LDCT-IR can be used instead of SDCT as the first-line imaging test because the ultimate clinical outcomes and diagnostic performance can be maintained if LDCT-IR is incorporated into the diagnostic process with selective additional imaging and clinical observation.

In this study, we observed that the use of LDCT-IR as a first-line imaging test was not inferior to SDCT with respect to the diagnosis of ureter stones and that it is clinically available for the evaluation of renal colic patients.