Dual-Energy CT Applications in the Abdomen

Transcription

1 Dual-Energy CT Review Dual-Energy CT Review Tobias Heye 1 Rendon C. Nelson Lisa M. Ho Daniele Marin Daniel T. Boll Heye T, Nelson RC, Ho LM, Marin D, Boll DT Keywords: abdomen, dual-energy CT, iodine extraction, tissue/material characterization, virtual unenhanced imaging DOI: /AJR Received May 4, 2012; accepted without revision May 8, Publication of this supplement to the American Journal of Roentgenology is made possible by an unrestricted grant from Siemens Healthcare. 1 All authors: Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC Address correspondence to D. T. Boll (daniel.boll@duke.edu). AJR 2012; 199:S64 S X/12/1995 S64 American Roentgen Ray Society Dual-Energy CT Applications in the Abdomen OBJECTIVE. The purpose of this article is to give a brief overview of the technical background of dual-energy CT (DECT) imaging and to review various DECT applications in the abdomen that are currently available for clinical practice. In a review of the recent literature, specific DECT applications available for abdominal organs, liver, pancreas, kidneys including renal stones, and adrenal glands, will be discussed in light of reliability and clinical usefulness in replacing true unenhanced imaging, increased lesion conspicuity, iodine extraction, and improved tissue/material characterization (e.g., renal stone composition). Radiation dose considerations will be addressed in comparison with standard abdominal imaging protocols. CONCLUSION. Modern DECT applications for the abdomen expand the use of CT and enable advanced quantitative methods in the clinical routine on the basis of differences in material attenuation observed by imaging at two different distinct photon energies. S everal dual-energy CT (DECT) applications became clinically available with the recent improvement and progress in CT technology. The potential of dual-energy technologies to improve tissue characterization and assess material composition was shown by early work in the 1970s and 1980s, but technical limitations at that time, such as prolonged data acquisition resulting in motion artifacts, prohibited the use of these concepts for clinical practice [1 4]. With these obstacles overcome today, DECT provides several advantages over singleenergy CT technology because of its ability to distinguish between substances of sufficiently different x-ray energy attenuation. The focus of this article is current applications in the abdomen that can be used to acquire additional information on tissue composition, allow the calculation of virtual unenhanced image sets, or provide improved conspicuity of iodine-containing enhancing lesions at lower energy levels compared with higher energy studies. Further DECT applications include improved temporal resolution, which can be used in CT angiography indications, and increased photon flux to better image obese patients. A brief outline of the theoretic concept of DECT is recapitulated followed by a review of organ-specific DECT imaging aspects for the liver, pancreas, kidneys, and adrenal glands structured in corresponding sections. Finally, dose considerations for the implementation of DECT are discussed in each section in comparison with single-energy CT. Theoretic Concept The concept of DECT is imaging at two distinctly different energies (e.g., 80 and 140 kvp) to obtain additional information regarding tissue composition compared with what singleenergy techniques can provide. Depending on the manufacturer, this can be achieved either by a setup of dual x-ray tubes and opposing detectors operated at two distinct energies or by using a setup of a single x-ray tube and a corresponding detector while rapidly switching between two different energies. Two basic considerations need to be embraced to explain the principles of DECT. The photoelectric effect, which is one of the mainstays at energy levels used in diagnostic imaging, refers to the interaction of matter with electromagnetic radiation. Energy, in the form of an incident photon, being absorbed by matter causes an electron to be emitted from the K- shell (the innermost shell) of an atom. Its place is then filled by an electron from the next higher shell, which emits an x-ray photon in the process. The K-shell s binding energy determines the probability of the photoelectric effect occurrence; as energy of the incident photon increases and approaches the K-shell binding energy, S64 AJR:199, November 2012

2 the effect becomes more likely. The K-shell binding energy is different for various elements and rises with higher atomic numbers. A sudden increase of attenuation, termed K-edge, is observed at photon energy levels just above the K-shell binding energy because these photons are more likely to be absorbed compared with photons just below the K-shell binding energy. Because the photoelectric effect, and therefore the K-edge, is energy dependent and linked to the atomic number, it is possible to derive information about a given element from the attenuation observed at different energy levels. If there is a sufficient difference in the K-edges of two elements, their attenuation observed at two distinct energies should be different and related to their specific K- edge, therefore allowing separation of these elements from each other and determination of their relative proportions. This concept is used in DECT, although these theoretic considerations are complicated by many factors, including noise, body habitus, and others, when applied to human tissue. The elements that compose the human body oxygen, carbon, hydrogen, nitrogen, calcium, and phosphorus (these elements make up 98.5% of the human body mass) are present in various combinations to form the different tissue types that are found in the human body. Although the K-edges of elements such as oxygen, carbon, hydrogen, and nitrogen are within the range of kev, the K-edges of calcium (4.0 kev) and iodine (33.2 kev) are much higher (Table 1). If two different energies are used for imaging, 80 and 140 kvp are used in most DECT applications, the attenuation differences observed allow distinguishing elements of sufficiently different K-edges [5]. Thus, calcium or iodine can be distinguished from soft tissues on the basis of their differences in K-edges. This is the basis for DECT applications, such as the calculation of virtual unenhanced imaging series, bone removal by subtraction of calcium, overlay of iodine maps onto standard CT images, and improved material characterization for distinguishing uric acid renal calculi from calcium salt or combined uric acid calcium salt calculi [6 8]. Virtual Unenhanced Imaging and Iodine Extraction Theoretically, the reconstruction of virtual unenhanced images has several advantages over true unenhanced imaging. To assess the enhancement characteristics of a lesion or tissue, its unenhanced attenuation is measured on true unenhanced imaging as part of a multiphase CT protocol. However, due to unpreventable motion or breathing artifacts, unenhanced and contrast-enhanced images may differ significantly on a pixel-by-pixel basis, in particular for smaller lesions. This adds unnecessary variation to CT density measurements by region of interest placements to evaluate the enhancement of a lesion or tissue. Hence, subtle differences in Hounsfield attenuation values caused by noise, artifacts, and different reconstruction algorithms may accumulate to pseudoenhancement, although there is no actual enhancement of the lesion in question. In DECT imaging, the datasets at two different photon energies are almost simultaneously acquired, which drastically limits the possibility of motion and enables comparison of attenuation values on a pixel-by-pixel basis if virtual unenhanced datasets are calculated. The DECT technology comes with the price of slightly increased radiation dose compared with a single-phase monoenergetic CT protocol, but often the incidental detection of a lesion requires the knowledge of its unenhanced Hounsfield attenuation value to further characterize it as benign versus potentially malignant. These circumstances often call for a dedicated multiphase CT examination with at least a dual-phase protocol because the presence of such lesions cannot not be anticipated (e.g., renal lesion with CT densities higher than 20 HU or incidentally discovered adrenal nodule). The resulting radiation dose to the patient by dual-phase CT is higher than the increase for single-phase DECT of the abdomen with the calculation of a virtual unenhanced series. The estimated radiation dose savings by omitting a true unenhanced series is reported to range from 19% to 50% [9 17]. The second generation of DECT technology imaging using energies at 80 and 140 kvp can be dose-neutral compared with single-energy CT at 120 kvp for pulmonary CT angiography if certain collimation restrictions are obeyed [18, 19]. Prior and ongoing studies show that CT density measurements performed on the reconstructed virtual unenhanced datasets do not differ in a clinically significant amount from true unenhanced datasets. Significant differences among attenuation values of various organs between true unenhanced and virtual unenhanced series were seen in a recent study. Organ-specific attenuation values were influenced by body habitus and organ enhancement, which is a function of organ vascularization [20]. The authors inferred that individualized DECT TABLE 1: Atomic Numbers and K-Edge Values for Elements Found in the Human Body and Various Contrast Materials Element Atomic Number (Z) K-Edge (kev) Hydrogen Carbon Nitrogen Oxygen Calcium Iodine Barium Gadolinium postprocessing algorithms are required to correct for these factors in the reconstruction of virtual unenhanced datasets, thus reducing unnecessary measurement variation. A study incorporating DECT phantoms to simulate normal and obese body habitus showed that iodine quantification is dependent on the reconstruction algorithm used and that iteratively reconstructed images showed less variation compared with standard backprojected datasets. Furthermore, DECT seemed to systematically overestimate iodine concentrations in lower concentration ranges and underestimate concentration ranges in higher concentration ranges (Feuerlein S et al., presented at the 2011 annual meeting of the American Roentgen Ray Society). A technical setup with two x-ray tubes and detectors, with one detector delivering a smaller FOV (26 cm in diameter), may limit the volume that can be covered by dualenergy imaging. A recent study showed that virtual unenhanced images including the complete abdominal circumference and all abdominal organs could be obtained in 23 of 40 patients. Incomplete coverage of the spleen or left kidney occurred in 11 patients, and the liver was not entirely imaged in six of 40 patients [10]. It can be hypothesized that these issues become more pronounced in patients with a greater body mass index and most likely larger abdominal circumference. Artifacts at the transition of the differently sized FOVs may be apparent, and incomplete iodine extraction on virtual unenhanced datasets could potentially cause diagnostic problems. Therefore, DECT offers the chance to eliminate true unenhanced imaging and to reconstruct virtual unenhanced series for diagnostic purposes if needed, but this comes with the risk of incom- AJR:199, November 2012 S65

3 plete coverage of the abdomen or the possibility of minor artifacts that may impair diagnostic image quality depending on the location of the lesions under scrutiny. Iodine extraction refers to a similar process as calculation of virtual unenhanced series. To reconstruct virtual unenhanced images, the attenuation caused by iodine on contrastenhanced DECT data must be quantified and separated from native soft-tissue attenuation and its relative contribution to each pixel value in the gray-scale range removed. Although this creates a virtual unenhanced image, the extracted data can be displayed as an image representing an iodine map that corresponds to a quantitative depiction of iodine distribution on contrast-enhanced DECT imaging. The identical process can be further refined to calculate absolute iodine content within a defined area or volume. The iodine map, color coded and overlaid onto morphologic imaging, in either virtual unenhanced or contrast-enhanced series may be used as visual support to identify enhancing lesions versus nonenhancement [17, 21, 22]. How virtual unenhanced series, iodine maps, and other DECT applications can be used for diagnostic purposes in various abdominal organs and how artifacts and limitations of DECT can affect clinical practice will be discussed in the next sections. Liver High lesion-to-liver contrast resulting in increased lesion conspicuity is desired for the detection of hypervascular malignancies such as metastases of renal cell carcinoma, neuroendocrine tumors, thyroid cancer, melanoma, breast cancer, or hepatocellular carcinomas. Because the K-edge of iodine (33.2 kev) is closer to lower energies (80 kvp) compared with higher energies (140 kvp), iodine is more attenuating at lower energies, resulting in improved conspicuity. This has been shown in phantom studies [23] and clinical evaluation [24]. In phantoms containing iodinated solutions to simulate hypervascular liver lesions, which were imaged at 80, 100, 120, and 140 kvp, the contrast-to-noise ratio (CNR) increased by a factor of 3.6 when comparing 80 with 140 kvp datasets [23]. The 80-kVp protocol resulted in the highest lesion conspicuity rated by three radiologists independently. These results were confirmed when applied to a clinical environment; 48 patients with 60 malignant hypervascular tumors where imaged at 140 and 80 kvp [24]. Although lower energies (80 kvp) resulted in increased image A noise as expected and consequently in lower image quality scores compared with 140 kvp, the CNR and lesion conspicuity scores were significantly higher at 80 kvp (Fig. 1). Additionally, imaging at lower energies resulted in a significantly lower effective radiation dose. In liver imaging, biphase or multiphase protocols are often required to adequately characterize hepatic lesions. Dual-energy techniques offer the possibility of subtracting iodine from contrast-enhanced datasets to reconstruct virtual unenhanced images of the liver parenchyma. This potentially reduces radiation exposure to the patient by eliminating the need for a true unenhanced acquisition. Image quality of virtual unenhanced and true unenhanced datasets of the liver parenchyma have been shown not to be significantly different, and acceptable diagnostic image quality was obtained in 95% of 40 cases compared with 97.5% for true unenhanced imaging [10]. The radiation dose reduction by implementing a portal venous DECT phase and omitting true unenhanced imaging was estimated at 30.5% ± 7.1%. The investigators in that study encountered image artifacts in the calculated virtual unenhanced datasets that compromised image quality. Major artifacts attributed to uncooperative patients and large body habitus were seen in two cases. Insufficient iodine extraction in small peripheral liver vessels was identified in all cases. In a few cases, iodine subtraction partially failed in the inferior vena cava (n = 2), adjacent to liver metastasis (n = 3), and the aorta (n = 1) without affecting image quality. Interestingly, the virtual unenhanced datasets showed significantly less noise compared with true unenhanced datasets, possibly because of the virtual nature, which involved added postprocessing algorithms. Similar results were reported by another study of 93 patients, comparing virtual unenhanced with true unenhanced datasets [25]. Although noise was always less on virtual unenhanced compared with true unenhanced imaging, attenuation values for the parenchyma of the liver, spleen, pancreas, and muscle measured in Hounsfield units on virtual unenhanced datasets calculated from arterial and portal venous DECT phases were not significantly C D Fig year-old man with hepatic metastases secondary to renal cell carcinoma (A and B) and 62-year-old man with hepatocellular carcinoma secondary to hepatitis C cirrhosis (C and D). A D, Arterial phase dual-energy CT imaging of liver at 80 kvp (A and C) and 140 kvp (B and D). Although 80-kVp images show more noise compared with 140-kVp images, they offer improved conspicuity of hypervascular lesions (arrows) because of increased iodine-to-tissue contrast. This effect is based on principle that iodine is more attenuating at 80 kvp because its K-edge (33.2 kev) is closer to 80 kvp than to 140 kvp. B S66 AJR:199, November 2012

4 different; however, fat and aorta differed significantly in Hounsfield units. Focal hepatic lesions showed similar CT density measurements on virtual unenhanced and true unenhanced images, but the signal-to-noise ratio was superior on virtual unenhanced images. The CNR comparison did not reveal any significant difference. Additional applications for DECT imaging of the liver include improved iron quantification in the presence of hepatic steatosis, which impairs iron measurement on single-energy CT [26, 27]. Although DECT seems reliable in creating virtual unenhanced datasets of the liver comparable to true unenhanced with the added benefit of lower radiation exposure and improved quantification applications, artifacts depending on the DECT technique and the body habitus appear to pose potential problems in a minority of cases. A D Fig year-old man who underwent right radical nephrectomy for T1a clear cell renal cell carcinoma. E F A F, Followup dual-energy CT (DECT) images reveal hyperdense renal cyst (insets) as shown by true unenhanced CT acquisition (A). Assessment of true enhancement versus pseudoenhancement is difficult on nephrographic (D) or arterial phase (B) images and often complicated by lesion size and partial volume averaging effects. Calculation of virtual unenhanced (C) series and iodine maps (F) clearly shows lesion hyperdensity without true contrast enhancement. Monoenergetic image series, for instance at 40 kev, can be calculated from DECT datasets to deliver improved iodine-to-tissue contrast (E). Pancreas Imaging of the pancreas relies on adequate contrast timing to depict the peak of parenchymal enhancement to maximize the contrast between typically poorly vascularized pancreatic malignancies and normal pancreatic parenchyma. Unfortunately, a fraction of pancreatic ductal adenocarcinomas (11%, six in 53 patients) may show isoattenuation, either due to tissue composition and similar vascularization compared with the remainder of the pancreas or as a result of inadequate contrast timing [28]. Improved CNR between pancreatic malignancies and normal parenchyma would offer increased detection rates of small or otherwise isoattenuating pancreatic tumors. A recent study has shown that imaging at 80 kvp results in significantly higher contrast enhancement of the pancreas and greater pancreas-to-tumor CNR [29] in late arterial phase imaging. The estimated effective radiation dose was decreased from 18.5 to 5.1 msv at the cost of slightly increased image noise for 80 kvp (11.5 HU) compared with 140 kvp (18.6 HU). Another B study has shown that virtual unenhanced images can be reliably extracted from pancreatic phase DECT datasets without significant differences in image quality, providing less image noise than true unenhanced imaging and an estimated 26.7% ± 9.7% reduction in radiation dose exposure to the patient [11]. Kidney Renal Lesions DECT techniques offer improved characterization of renal calculi and differentiation between simple renal cysts and enhancing cystic lesions. Commonly encountered as an incidental finding on single-energy portal venous phase CT of the abdomen, renal Fig. 3 Examples of renal stone appearance on dual-energy CT (DECT) images created from advanced postprocessing algorithm that analyzes relative differences in attenuation values of renal stones at low (80 kvp) and high (140 kvp) energy DECT datasets. Postprocessing allows successful differentiation of renal stone subtypes on basis of attenuation values that are not based on Hounsfield system conventions (attenuation in ascending order from left to right) [7, 43]. Distinct margins around visualized renal stones are related to blooming phenomena at different x-ray tube voltages. C AJR:199, November 2012 S67

5 cysts require the visualization of simple fluid attenuation (< 20 HU) and nonenhancement (< HU difference between unenhanced and contrast-enhanced CT) to be classified as simple benign cysts (Bosniak type I). If a renal lesion shows attenuation values above 20 HU, differential considerations extend from benign high-attenuation cysts (Bosniak type II) to enhancing solid renal lesions, in particular renal cell carcinoma (RCC). Because most renal lesions are found incidentally on CT, which is not routinely tailored to characterize renal lesions, a dedicated dual-phase renal CT examination is often necessary to evaluate lesion enhancement on the basis of attenuation differences on unenhanced and contrast-enhanced image acquisitions. Furthermore, dedicated renal imaging involves additional contrast administration with the risk of kidney injury and increased radiation exposure and health care costs. DECT can provide virtual unenhanced datasets from a single-phase CT examination without substantial increase in radiation dose compared with single-energy CT [21]. A A study including 139 focal renal lesions has shown that virtual unenhanced datasets are equivalent to true unenhanced series without significant differences in attenuation for simple cysts, hyperdense cysts, fat-containing lesions (e.g., angiomyolipomas), and solid enhancing renal lesions, thus allowing confident diagnosis on the basis of single-phase DECT acquisition and the calculation of virtual unenhanced datasets [30] (Fig. 2). Many similar studies support the potential of DECT in the characterization of renal lesions while also showing that up to 50% of radiation dose can be spared by the omission of true unenhanced acquisition [12 17]. Use of color-coded iodine maps overlaid onto virtual unenhanced or contrast-enhanced series may reduce interpretation time and facilitate the detection of contrast enhancement [12, 14, 17]. Renal Calculi In clinical practice, single-energy MDCT is a routine application for fast and reliable detection and localization of renal calculi. The composition of renal calculi may include substances such as calcium oxalate, uric acid, cystine, calcium phosphate, brushite, and struvite (ammonium, magnesium, and phosphate) and is of great clinical importance because it influences, treatment options and approach. Uric acid stones, which comprise approximately 10% of the renal stones encountered in the affected population in the United States, are treated by urine alkalization [31]. As a consequence, characterization of stone composition and identification of specific renal stone types affects patient management. Although single-energy CT cannot differentiate between different renal stone manifestations, there is evidence that DECT may allow characterization of renal stone composition and offer stone detection on nephrographic phase imaging or in contrast-filled collecting systems by the use of iodine subtraction techniques [6, 7, 32 42]. It has been shown that advanced postprocessing of renal stone DECT data is capable of discriminating various renal stone types, including calcium-containing subgroups, in an in vivo setting [43] (Fig. 3). The knowledge of renal stone composition may allow targeted preventive therapy and immediate initiation of stone-specific treatment, D E F Fig year-old man with hematuria. A F, Nephrographic phase dual-energy CT (DECT) image (A) of abdomen reveals incidental nodule in left adrenal gland. True unenhanced (TNC) (D) image shows attenuation values of 8.9 HU, and virtual unenhanced (VNC) (E) dataset calculated from contrast-enhanced DECT shows 9.9 HU (B). Both datasets allow diagnosis of benign adrenal adenoma. Iodine map is shown in gray scale (F) and color coded (C). Arrows indicate nodule. White ovals indicate smaller 26-cm FOV of second x ray tube and detector array in dual-source CT setup. B C S68 AJR:199, November 2012

6 and it may predict success of shockwave lithotripsy. However, a study comparing detection rate of 80 renal calculi on true unenhanced and virtual unenhanced series calculated from nephrographic and excretory phase DECT imaging revealed that 18 (virtual unenhanced from nephrographic phase) and 21 (virtual unenhanced from excretory phase) small renal calculi ranging from 1 to 3 mm were missed [44]. Nevertheless, stones detected by virtual unenhanced series on nephrographic and excretory phase imaging ranged from 1 to 19 mm in size. Difficulties in detecting renal calculi on virtual unenhanced series were attributed to inferior image quality compared with true unenhanced series. These results are not entirely discouraging because missed stones in the range of 1 3 mm in size are less likely to cause significant problems in clinical management. On the other hand, this finding shows that virtual unenhanced imaging may not be able to fully replace the reference standard true unenhanced imaging at this point. Adrenal Adrenal nodules are mostly discovered incidentally on routine abdominal CT and are identified in 4 5% of abdominal CT examinations [45, 46]. Although statistically benign in the majority of cases [47], additional testing is often needed to confirm benignity or to exclude the possibility of a nonadenoma or metastasis. Especially in patients with a history of malignancy, further characterization is required if an adrenal nodule is incidentally discovered on imaging performed for staging purposes. In the majority of cases, dedicated adrenal imaging would be necessary to show attenuation less than 10 HU on unenhanced CT, which is generally accepted to confidently diagnose the presence of microscopic lipid within an adenoma [48]. However, dedicated imaging using CT or MRI showing lipid content within the adrenal lesion or contrast washout, with various thresholds ranging between 35 60%, are found in the literature. Because unenhanced CT is not routinely acquired in clinical practice, 10- or 15-minute delayed phase imaging may be required [49]. One study reported that 38% of adrenal nodules incidentally discovered by CT were not adequately characterized by initial imaging [46]. Additional health care costs and delay in treatment caused by dedicated adrenal imaging may be preventable with the use of DECT by calculation of virtual unenhanced series for the characterization of adrenal nodules (Fig. 4). Evidence suggests that benign adenomas show a decrease in attenuation at 80 kvp compared with 140 kvp, equivalent to the presence of intracellular lipid, resulting in 50% sensitivity, 100% specificity, 100% positive predictive value, and 28% negative predictive value in the diagnosis of adenoma as shown by a study on 26 adrenal nodules (5/26 metastasis) [50]. Because of the small number of reported cases, further evidence is needed to use these attenuation differences as a diagnostic tool. Subtraction of iodine and reconstruction of virtual unenhanced series from contrast-enhanced DECT may improve diagnosis of adrenal nodules. A recent study including 23 incidentally discovered adrenal nodules (19 adenomas, four metastases) showed the equivalence of virtual unenhanced and true unenhanced series in attenuation values (14.7 HU ± 15.1 HU and 12.9 HU ± 13.4 HU, respectively), with a mean difference of 1.8 HU ± 1.7 HU for adrenal nodules [51]. When virtual unenhanced series were used, no malignant nodules were misdiagnosed and strong agreement between virtual unenhanced and true unenhanced series, ranging from 83% to 91% for three radiologists, was found. Similar results were shown by another study investigating 51 adrenal masses in 42 patients, again true unenhanced and virtual unenhanced series showed no significant differences in attenuation values (5.9 HU ± 21.0 HU vs 7.0 HU ± 20.6 HU) [52]. Summary Initially described and investigated in the 1970s and 1980s, DECT has overcome previous limitations related to prolonged data acquisition resulting in motion artifacts. Recent technology improvements have facilitated the maturation of DECT into a reliable clinical tool that can be applied to various tasks in abdominal CT. The principle of imaging at two distinctly different photon energies allows separation of substances with sufficiently different K-edges, in particular soft tissue, iodine, and calcium. Implementation of DECT in abdominal CT provides a variety of applications to improve tissue characterization. Reconstruction of virtual unenhanced series can be used in the assessment of renal or adrenal lesions incidentally detected by single-phase contrast-enhanced DECT while considerably reducing radiation dose compared with a dual-phase, single-energy CT protocol with true unenhanced acquisition. Imaging at lower energies (80 kvp) optimizes conspicuity of hypervascular lesions in solid organs, and iodine maps can be superimposed on morphologic imaging to show contrast enhancement. Advanced postprocessing DECT applications include the discrimination of various renal stone types and the quantification of hepatic iron deposition, even if complicated by the presence of hepatic steatosis. 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