Compound analysis of gallstones using dual energy computed tomography—Results in a phantom model

Abstract

Purpose

The potential of dual energy computed tomography (DECT) for the analysis of gallstone compounds was investigated. The main goal was to find parameters, that can reliably define high percentage (>70%) cholesterol stones without calcium components.

Materials and methods

35 gallstones were analyzed with DECT using a phantom model. Stone samples were put into specimen containers filled with formalin. Containers were put into a water-filled cylindrical acrylic glass phantom. DECT scans were performed using a tube voltage/current of 140 kV/83 mAs (tube A) and 80 kV/340 mAs (tube B). ROI-measurements to determine CT attenuation of each sector of the stones that had different appearance on the CT images were performed. Finally, semi-quantitative infrared spectroscopy (FTIR) of these sectors was performed for chemical analysis.

Results

ROI-measurements were performed in 45 different sectors in 35 gallstones. Sectors containing >70% of cholesterol and no calcium component (n = 20) on FTIR could be identified with 95% sensitivity and 100% specificity on DECT. These sectors showed typical attenuation of −8 ± 4 HU at 80 kV and +22 ± 3 HU at 140 kV. Even the presence of a small calcium component (<10%) hindered the reliable identification of cholesterol components as such.

Conclusion

Dual energy CT allows for reliable identification of gallstones containing a high percentage of cholesterol and no calcium component in this pre-clinical phantom model. Results from in vivo or anthropomorphic phantom trials will have to confirm these results. This may enable the identification of patients eligible for non-surgical treatment options in the future.

Introduction

Gallstones and their medical consequences represent a relevant cost factor in healthcare systems of Western countries. In Germany, 10.5–24.5% of the female and 4.9–13.1% of the male population are estimated to carry gallstones, and about 170,000 cholecystectomies are performed annually [1]. In the United States of America, gallstone disease causes over 700,000 cholecystectomies per year, which is reflected in the health care budget with annual expenses of 6.5 billion USD [2]. The diagnosis of gallstone disease is usually made by clinical presentation, laboratory constellation, and the proof of stone by imaging modalities (mostly ultrasound, endoscopic retrograde or magnetic resonance cholangio-pancreaticography, or computed tomography). Most of the persons carrying gallstones will never develop symptoms. But if gallstone disease becomes evident – mostly as acute cholecystitis or biliary colic – the therapy is very straight forward: whenever possible, definite cure will be sought by removing stones. However, not every patient is eligible for invasive treatment due to personal risk profiles. Further, surgical treatment bears a certain potential of risk inherent in its invasive nature and required anaesthesia.

For the above reasons, early detection of gallstones, that may be suitable for non-invasive treatment options, has always been of great interest. Established methods are extra-corporal shockwave lithotripsy (ESWL) and pharmacological dissolution therapy with gall acids [3], [4] – either alone or in combination – and contact dissolution with methyl tert-butyl ether [5]. Recently, first experiences with ezetimibe could show promising results [6]. However, for successful dissolution the identification of high content cholesterol stones is important, as only these stones seem to show satisfying result [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13].

In the past, several authors have described computed tomography (CT) for compound differentiation of gallstones [9], [14], [15], [16], [17], [18], [19], [20], [21], [22]. Results were inconsistent in terms of reliable differentiation of cholesterol to other components, because confidence intervals overlapped, attenuation thresholds to define a cholesterol stone varied, and scanner settings and methods for chemical analysis differed markedly. Further, regular single source scanners with only one X-ray tube were used and stones were mainly scanned at only one predefined tube voltage. Recently a dual source CT (DSCT) system has become available for clinical routine [23], [24]. The possibility to operate both tubes at different potentials (dual energy CT; DECT) has brought the option for material and tissue differentiation into clinical routine [25], [26].

In this proof-of-concept study, we investigated the potential of DECT for compound analysis of gallstones in a phantom model under optimized in vitro conditions. Findings were compared to semi-quantitative Fourier transform infrared spectroscopy (FTIR), which served as the reference standard for chemical gallstone analysis. The main goal of this study was to define parameters that could reliably define gallstone components with a high content (>70%) of cholesterol and no calcium components (“pure” cholesterol components) on DECT.