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Dual energy spectral CT imaging of insulinoma—Value in preoperative diagnosis compared with conventional multi-detector CT
European Journal of Radiology 81 (2012) 2487–2494
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Dual energy spectral CT imaging of insulinoma—Value in preoperative diagnosis compared with conventional multi-detector CT Xiao Zhu Lin a,∗,1 , Zhi Yuan Wu a,1,2 , Ran Tao b,3 , Yan Guo c,4 , Jian Ying Li d,5 , Jing Zhang a,2 , Ke Min Chen a,6 a
Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197, 2nd Ruijin Road, Shanghai 200025, China Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197, 2nd Ruijin Road, Shanghai 200025, China Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197, 2nd Ruijin Road, Shanghai 200025, China d General Electricity CT Research Center, 1 Yongchang North Road Beijing Economic and Technologic Development Area, Beijing 100176, China b c
a r t i c l e
i n f o
Article history: Received 22 August 2011 Received in revised form 23 October 2011 Accepted 26 October 2011 Keywords: Insulinoma Spectral CT imaging Multi-detector CT Diagnosis
a b s t r a c t Objective: The aim of this study was to investigate the value of dual energy spectral CT (DEsCT) imaging in preoperative diagnosis of insulinomas in comparison with conventional multi-detector CT (MDCT). Materials and methods: Thirty-five patients were included in this study with 14 underwent the conventional dual-phase CT imaging (from March 2009 to January 2010) and 21 underwent the dual-phase DEsCT imaging (from February 2010 to May 2011). CT images were interpreted prospectively by two radiologists in consensus before operation. All the patients had diagnosis confirmed pathologically. The accuracy of preoperative diagnosis of insulinomas between DEsCT imaging and conventional MDCT, and between different kinds of images of DEsCT was compared. Results: There were 39 confirmed lesions among the 35 patients (23 and 16 tumors in the spectral CT group and MDCT group, respectively). MDCT detected 11 of 16 tumors. DEsCT imaging detected 20 of 23 tumors separately with the monochromatic image or the iodine density image, and 22 of 23 tumors with the combination of the two kinds of images. The sensitivity for the preoperative diagnosis of insulinoma was 95.7% with the combination of monochromatic and iodine density images in DEsCT imaging, statistically higher than that with the conventional MDCT (68.8%) (p = 0.033). Conclusion: Dual energy spectral CT imaging has higher sensitivity in preoperative diagnosis of insulinomas compared with conventional MDCT. The combination of monochromatic image and iodine density image can improve the diagnostic sensitivity of insulinomas. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Fasting hypoglycemia in healthy, well nourished adults is rare and is most commonly due to an adenoma of the islet of Langerhans, called insulinoma. Insulinomas are challenging lesions, difficult to
∗ Corresponding author. Tel.: +86 13764236797; fax: +86 2164661351. E-mail addresses: lin xiaozhu [email protected] (X.Z. Lin), [email protected] (Z.Y. Wu), [email protected] (R. Tao), [email protected] (Y. Guo), [email protected] (J.Y. Li), [email protected] (J. Zhang), [email protected] (K.M. Chen). 1 These authors contributed equally. 2 Tel.: +86 13564620606. 3 Tel.: +86 13301919116. 4 Tel.: +86 13918548754. 5 Tel.: +86 13910081465. 6 Tel.: +86 13701769751. 0720-048X/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2011.10.028
diagnose. Although insulinomas are very rare tumors, they are the most common functioning pancreatic endocrine tumors. The incidence in general population is 1–4 per 1,000,000 yearly but the incidence is higher in autopsy studies (0.8–10%) [1]. Insulinomas are usually small (1–2 cm) and can be difficult to localize; thus preoperative localization is key to successful surgical management. Due to the potent nature of insulin, even a tumor that is too small to localize with conventional imaging modality can produce debilitating and even life-threatening symptoms such as severe hypoglycemia, which results in neurologic dysfunction and symptoms of neuroglycopenia: confusion, visual disturbances, loss of consciousness, seizures, or rarely focal neurologic deficits resembling stroke. Operative removal of the tumor is the mainstay of treatment, but is predicated on precise preoperative localization. Many diagnostic modalities have been reported for the localization of insulinoma and can be either invasive or non-invasive. Computed tomography (CT) is the first choice for imaging [2,3]. Technical
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Fig. 1. 29-Year-old man with an 8-mm insulinoma in the pancreatic head. (A) Monochromatic image with 70 keV in arterial phase did not show lesion clearly. (B) Iodine density image showed focally hyper-density in the pancreatic head (white arrow). (C and D) Optimal contrast to noise ratio (CNR) analysis based on iodine density image. (E) Optimal monochromatic image at 49 keV showed focally hyper-attenuation in the pancreatic head (white arrow).
advances have led to the improvement in the quality of CT in terms of scan speed, coverage and spatial resolution. Studies with retrospective method have suggested improved performance for the detection of insulinomas with sensitivity from 83% to 94% [4–6] while the prospective detection rate is still very low, and was 63% in one of the studies [4]. Dual energy CT using dual tube voltages with either two consecutive scans or dual X-ray source-dual detector assembly has existed for a number of years to provide additional information for material separation with imaging [7–11]. Recently a dual energy spectral CT (DEsCT) imaging mode based on the rapid switching between highand low-energy data sets from view to view was introduced to produce both the material decomposition images and monochromatic spectral images. This scanning method has also found its use in several clinical applications including image quality improvement, diagnosis of pulmonary embolism, and differentiated diagnosis of hyper-vascular hepatic lesions [12–15]. In this study we investigated the clinical values of DEsCT imaging, a new technique for pancreatic imaging, for detection of insulinomas. The purpose of
this study was to evaluate the sensitivity of preoperative diagnosis of insulinoma with DEsCT imaging compared with a conventional multi-detector CT (MDCT).
2. Materials and methods 2.1. Patients This is a small sample single center study. All the patients were diagnosed and treated in our hospital. This study was approved by our institutional ethics committee. For the DEsCT imaging group (group 1), from February 2010 to May 2011, 21 patients [8 men, 13 women; median age 47 (13–81 years)] underwent dual-phase CT scans on a High Definition CT system (Discovery CT750HD, GE Healthcare, Milwaukee, Wisconsin, USA) with dual energy spectral imaging mode. The duration of symptoms (repeated episodes of hypoglycemia) of the 21 patients was from 3 months to 12 years (median time 2.75 years).
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For the MDCT group (group 2), clinical information of 14 patients [3 men, 11 women; median age 49 (26–71 years)] with insulinomas who had undergone conventional dual-phase CT scans from March 2009 to January 2010 on a 64-detector CT scanner (LightSpeed VCT, GE Healthcare, Milwaukee, Wisconsin, USA) were retrospectively reviewed. The duration of symptoms (repeated episodes of hypoglycemia) of these 14 patients was from 1 week to 16 years (median time 4.5 years). All the patients were operated after the diagnosis. The final diagnosis of insulinoma was made by histopathological examinations. 2.2. CT scans 1000 ml water was given over 15–20 min before the scanning. All patients were scanned craniocaudally in supine position. Unenhanced scans were acquired following scout scans with the conventional helical scan mode at 120 kVp tube voltage. Other parameters for the unenhanced scan include: collimation thickness 0.625 mm × 64, rotation time 0.6 s, pitch 0.984, auto mA with noise index 12. The unenhanced CT acquisition was used to localize the pancreas. Patients were then injected nonionic contrast medium (Iopamidol Injection, Iopamiro 300; Shanghai BRACCO Sine Pharmaceutical Corp. Ltd., China) via antecubital venous access by using a power injector (Ulrich medical, Germany) at a rate of 3–4 ml/s for a total of 80–100 ml during the arterial (AP) and portal venous phase (PP). The scanning delay for AP imaging was determined using a semi-automatic scan-triggering software (SmartPrep; GE Healthcare). AP scanning began 8 s after the trigger attenuation threshold (80HU) was reached at the level of the supra-celiac abdominal aorta. For the PP, the delay was 30 s after the end of AP. The acquisition of AP covered the whole pancreas and the acquisition of PP included the entire liver and pancreas. For group 1, both AP and PP were scanned with dual energy spectral imaging mode with fast tube voltage switching between 80 kVp and 140 kVp on adjacent views during a single rotation. Other scanning parameters were as following: collimation thickness: 0.625 mm × 64, SFOV: 50 cm, tube current: 600 mA, rotation speed: 0.6 s, helical pitch: 0.983. CTDIvol for the spectral CT mode was 21.8 mGy. Images were reconstructed with projection-based material decomposition software and a standard recon kernel. Waterand iodine-based material decomposition images and monochromatic images at energy levels ranging from 40 keV to 140 keV (with default level at 70 keV) were reconstructed from DEsCT acquisition. All images were reconstructed with 2.5 mm slice thickness. For group 2, the scanning parameters were as following: helical mode, collimation thickness: 0.625 mm × 64, SFOV: 50 cm, kV: 120 kVp, tube current: 250–550 mA, rotation speed: 0.8 s, helical pitch: 0.984. CTDIw values for this scan mode were from 12.0 mGy to 36.9 mGy. The average CTDI value for this group patients with conventional helical scanning was 20.1 mGy (±6.0 mGy), similar to that in the spectral CT mode. Images were reconstructed with a standard recon kernel, slice thickness 2.5 mm. 2.3. Image analysis CT images were interpreted prospectively for both groups by two radiologists (with 5 and 15 years of experience of abdominal imaging, respectively) before operation. The two radiologists recorded the lesion number, location [head (including uncinate process), neck, body, tail of pancreas] and size (the largest dimension) and made the final diagnosis by consensus. For group 1: the dual energy spectral image sets (iodine-based material decomposition images and the 101 sets of monochromatic images) were loaded on an advanced workstation (AW4.4; GE Healthcare, Waukesha, Wisconsin, USA) with the Gemstone Spectral Imaging viewer (GSI viewer, GE Healthcare, Waukesha,
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Wisconsin). GSI viewer allows the review of both the monochromatic energy images at a user selectable energy level for anatomic analysis, and the iodine-based material decomposition images for the quantitative iodine concentration analysis. The default monochromatic images (at 70 keV) and iodine-based material decomposition images were reviewed independently first and then combined for the initial reading. If any unusual enhancement in the pancreas was noted, using the lesion location determined on either image, the contrast-to-noise ratio (CNR) was calculated for the lesion with the region-of-interest (ROI) on the potential lesion and the normal pancreas parenchyma as background. The GSI viewer software package automatically propagated the CNR measurements for the 101 sets of monochromatic images and displayed the CNR values as function of photon energies. From the CNR-energy level plot, the optimal single energy (keV) level for generating the best CNR between the pancreatic lesion and the pancreas parenchyma was selected and the final imaging diagnosis was made on the monochromatic images with the optimal energy level (Fig. 1). For group 2: the conventional CT images (from MDCT) were interpreted through the Picture Archiving & Communication System in our hospital. 2.4. Statistical analyses The data was analyzed using SPSS13 (Chicago, IL, USA). Quantitative values were recorded as mean ± standard deviation for the size of tumor or median ± interquartile range for the age, duration of symptoms, time between CT scan and operation. The statistical significance level was set at 0.05. Independent sample tests were used for comparing the tumor size (t-test), age, duration of symptoms and time between CT scan and operation (Mann–Whitney test) between two groups. Chi-square test (Fisher’s exact) was used to compare the gender composition and tumor location between two groups. Chi-square test (Fisher’s exact) was used to compare the sensitivity of preoperative detection of insulinomas between the conventional MDCT and spectral CT imaging, and between different kinds of images of spectral CT. 3. Results During the study period, all the patients were underwent surgical resection [16 enucleation, 14 distal pancreatectomy (+/− splenectomy), 2 middle segmental pancreatic resection, 2 pancreatic head resection (+/− duodenum-preserving), and 1 laparoscopic distal pancreatectomy]. The median time between the CT scan and operation was 15 days (range 2–30 days) for group 1 and 7 days (range 3–25 days) for group 2. There were no significant differences on the patient age, gender composition, duration of symptoms, time between CT scan and operation between two groups (Table 1). Tumor samples were obtained by resection. The size of each tumor and the number of tumors were recorded. Twenty-three tumors in group 1 (21 patients, two patients had two lesions) and 16 tumors in group 2 (14 patients, one patient had 3 lesions) were identified by histopathological diagnosis. In group 1 ten tumors located in pancreatic head and neck, 12 in body and tail, and one tumor was exophytic (from uncinate process). In group 2 seven tumors located in pancreatic head and neck, 8 in body and tail, and one tumor was ectopic (below uncinate process). The average tumor size was 1.2 ± 0.5 cm (0.5–2.0 cm) for group 1 and 1.5 ± 0.5 cm (0.6–2.5 cm) for group 2 patients. There were no significant differences on tumor size, tumor location between two groups (Table 2). In group 1 with the dual energy spectral imaging, the optimal energy levels based on CNR measurement for pancreatic tumors were in the 45–60 keV range. The monochromatic image at the
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Table 1 Comparison of general information of the patients between two groups. Group
N
Sex
Age (y)[M ± (Q3 − Q1 )]
T1 (y)[M ± (Q3 − Q1 )]
T2 (day)[M ± (Q3 − Q1 )]
Spectral CT MDCT
21 14
8m:13f 3m:11f
47 ± 21 49 ± 22
2.5 ± 4.0 4.5 ± 4.0
15 ± 11 7±9
2 = 1.083 0.461
Z = −0.101 0.919
Z = −1.180 0.238
Z = −1.670 0.095
P
N: number of cases, m: male, f: female, y: year, M: median, Q3 − Q1 : interquartile range, T1: duration of symptoms, T2: time between CT scan and operation, 2 : Chi-square, Fisher’s exact, Z: Mann–Whitney test.
Table 2 The comparison of the tumors and the detection rate of tumors between two groups. Group
N
Location
Size (cm)
Sensitivity
a
23 16
10h–n:12b–t:1 exo 7h–n:8b–t:1ect
1.2 ± 0.5 1.5 ± 0.5
95.7%(22/23) 68.8%(11/16)
2 = 0.385 1.000
t = −1.502 0.142
2 = 5.246 0.033
Spectral CT MDCT P
a Spectral CT with combination of monochromatic image and iodine density image; N: number of tumors, h–n: head and neck, b–t: body and tail, exo: exophytic, ect: ectopic, 2 : Chi-square, Fisher’s exact, t: two sample independent t-test.
Table 3 The detection rate of insulinoma on different kinds of image sets.
Sensitivity
MDCT
Mono
Iodine
Mono + iodine
68.8%(11/16)
87.0%(20/23)
87.0(20/23)
95.7%(22/23)
= 1.918 0.235
= 1.918 0.235
2 = 5.246 0.033
2
2
P
MDCT: multidetector CT; mono: default monochromatic image with energy level at 70 keV; iodine: iodine density image; mono + iodine: monochromatic images combined with iodine density images; P: Chi-square test between MDCT image and spectral CT image (monochromatic image, iodine density image, monochromatic images combined with iodine density images).
optimal energy level alone detected 20 of 23 tumors (87.0%), and the iodine density image detected 20 of 23 tumors (87.0%). With the combination of both the monochromatic and iodine density image sets spectral CT imaging detected 22 of 23 tumors (95.7%). In group 2, the conventional MDCT detected 11 of 16 tumors (68.8%) (Table 3). There was no significant difference between monochromatic image and iodine density image on the detection rate (p = 1.000). Even though the detection rates with either the monochromatic image (87.0%) or the iodine density image (87.0%) independently were higher than that of the conventional MDCT (68.8%), they were not statistically significant (p = 0.235). However, there was significant difference for the sensitivity for preoperative diagnosis of insulinoma between DEsCT imaging with the two image sets combined and the conventional MDCT (p = 0.033, 2 = 5.246) (Table 3). In group 1, the conventional MDCT missed 5 insulinomas: 10mm insulinoma in the body and tail, three insulinomas (with size 12 mm, 15 mm, and 6 mm) in the pancreatic head, and one 15-mm insulinoma ectopic which was below the uncinate process of the pancreas. Among these tumors, one tumor was too small (6 mm) to be detected either by CT or by MRI, one tumor was ectopic and moderately enhanced, and the other three tumors had the enhancement similar to the pancreatic parenchyma with the 120 kVp polychromatic X-ray source which had an average energy of about 70 keV for the patients. Two of the five tumors could be confirmed retrospectively. Three of the 5 tumors were detected by MRI, and one of the patients was diagnosed by selective arterial calcium stimulation and hepatic venous sampling before the surgery (Fig. 2). The patient with a 6 mm lesion missed had another 20 mm lesion and thus been operated. In group 2, the use of monochromatic image alone initially missed three tumors: two tumors in the pancreatic head (with size 8 mm and 5 mm), and one 6 mm insulinoma in the pancreatic tail. The two tumors in the pancreatic head were iso-attenuating to the pancreas on monochromatic image with the default 70 keV
energy level, but they were hyper-dense on the iodine images and the optimal monochromatic images with 40 keV and 49 keV (Fig. 3). The tumor in the pancreatic tail could not been found either on the monochromatic images or on the iodine images. The other two tumors missed by iodine images had hypo-density: 20 mm insulinomas in the body and tail, and 18 mm insulinoma in the uncinate process. The monochromatic images detected these two hypo-attenuation tumors (Fig. 4). 4. Discussion The sensitivity for preoperative detection of insulinomas with the dual energy spectral CT imaging using both the material decomposition images and monochromatic images generated from the single acquisition was 95.7% (22/23), which was higher than that of conventional MDCT (68.8%, 11/16) in this study and was also higher than the results of previous studies [3–6,16]. In this study, the conventional MDCT missed 5 insulinomas. Two of the five tumors could be confirmed retrospectively. Three of the 5 tumors were detected by MRI, and one of the patients was diagnosed by selective arterial calcium stimulation and hepatic venous sampling before the surgery (Fig. 2). For the DEsCT, the use of monochromatic image alone initially missed three tumors. Two of the three tumors were iso-attenuating to the pancreas on monochromatic image with the default 70 keV energy level, but with the adjustment of energy levels for the monochromatic image sets from the default 70 keV to the optimal ones, these two tumors were detected (Fig. 3). One of the three tumors could not been found either on the monochromatic images or on the iodine images. It might be too small and iso-attenuating. Two tumors missed by iodine images had hypo-density, and the monochromatic images detected these two hypo-attenuation tumors. It might because of the lower image noise and higher CNR of the monochromatic image compared to the iodine images. Therefore, with the combination of
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Fig. 2. 37-Year-old woman with a 10-mm insulinoma in the junction of pancreatic body and tail. (A and B) Conventional MDCT image in arterial phase and portal venous phase showed iso-attenuation lesion in the junction of pancreatic body and tail. (C–F) MRI images of the same patient. T2 weighted image showed hyper-intensity lesion (C), T1 weighted image with fat suppression showed hypo-intensity lesion (D), T1 weighted image in arterial phase showed iso-intensity lesion (E), and T1 weighted image in portal venous phase showed iso-intensity lesion (F) in the junction of pancreatic body and tail.
the monochromatic image and iodine image, the insulinomas with uncommon characteristic such as iso- or hypo-attenuation could also be detected successfully. This can improve the sensitivity of preoperative diagnosis for the insulinomas. The averaging attenuation effect of polychromatic X-rays in conventional CT imaging reduces the low-contrast resolution between materials. In addition, beam hardening caused by the preferential absorption can shift the HU value for a material within the scan field of view of a patient or between patients. Because of beam hardening artifacts, CT numbers are sometimes unreliable for enhancing/nonenhancing verification in small lesions. On the other hand, spectral CT imaging provides the monochromatic images depicting how the imaged object would look if the X-ray source produced only single energy X-ray photons. This would allow for eliminating the beam hardening artifacts and averaging attenuation effects [12], as well as for increasing contrast resolution. According to the density of the lesion and the background, GSI viewer could provide an optimized energy level and on the optimal monochromatic images the lesion was displayed with the best CNR which further improved the lesion detection rate [13]. Because of the scanner limitation we did not compare the monochromatic images obtained with fast-switching technique with that of dual-source method where images from the
two tube-detector assemblies were reconstructed individually and then combined with different weights. However, it was pointed out by previous researchers that the monochromatic images generated from the raw-data reconstructed may be superior to the imagebased method in terms of less susceptible to the beam hardening artifacts [17,18]. For medical diagnostic imaging, water and iodine are often selected as the basis pair for material decomposition image presentation because their atomic numbers span the range of atomic numbers for materials generally found in medical imaging and approximate those of soft tissue and iodinated contrast material to result in material-attenuation images that are intuitive to interpret. For the small hypervascular lesions such as insulinoma, small hepatocellular carcinoma and small hepatic hemangioma, iodine density image could be very sensitive, showing focal uptake of the iodinated contrast material [14]. And the small lesion could be isoattenuation on the conventional CT images because of the averaging attenuation effect of polychromatic X-rays. Multiple imaging options are available for preoperative localization of insulinomas, including trans-abdominal ultrasound, CT, MRI, endoscopic ultrasound (EUS), and angiography with intraarterial calcium stimulation testing [19,20]. The availability and
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Fig. 3. 53-Year-old woman with an 8 mm insulinoma in the pancreatic head. (A) Monochromatic image with 70 keV in arterial phase did not show lesion clearly. (B) Iodine density image showed focally hyper-density in the pancreatic head (white arrow). (C) Optimal monochromatic image at 40 keV showed focally hyper-attenuation in the pancreatic head (white arrow). (D) Monochromatic image with 70 keV in portal venous phase did not show lesion clearly. (E) Iodine density image showed slightly focal hyper-density in the pancreatic head (white arrow). (F) Optimal monochromatic image at 49 keV showed slightly hyper-attenuation in the pancreatic head (white arrow).
success rates of imaging and localization techniques vary between institutions. Improvements in MDCT technology have allowed optimization of the scanning protocols with rapid scan times, which reduces movement artifacts and allows accurate contrast medium bolus tracking. This ensures optimal timing of the scan and excellent arterial-phase images and permits image reconstruction in thinner slices, which results in improved image resolution and the sensitivity of preoperative detection [21]. Some of the previous studies have demonstrated that MRI is superior to other preoperative imaging techniques in identifying small pancreatic insulinomas [22]. Its sensitivity ranges from 71% to 95% in the detection of insulinomas and the determination of the presence of metastases [16,22–24]. The main limitation of MRI is that the quality of the examination seriously depends on the cooperation of the patients, especially for the detection of small lesions. In this study, only 13 patients with 15 lesions (65.2%, 15/23) had MRI in the group of DEsCT imaging. In the prospective diagnosis, MRI missed 7 lesions (sensitivity: 53.3%, 8/15). During the retrospective review of the images, two more lesions were confirmed with the sensitivity of 66.7%, which is similar to conventional MDCT while lower than DEsCT in this study. EUS can also provide useful information about tumor size and proximity to surrounding structures, but it requires operator expertise in both advanced
endoscopy and ultrasound. We had very limited experience with EUS for insulinomas, even though it was reported to have higher sensitivity (75–89%) than either CT scan or abdominal ultrasound in identifying small tumors as reported in the previous studies [16,24]. However, like traditional trans-abdominal US, the images obtained are typically less helpful to the operating surgeon. Our study does have some caveats. First, this investigation reflects our preliminary experience in a small number of patients. Larger sample study needs to be performed to validate our results. Second, in this study we compared DEsCT imaging and conventional MDCT with different groups of patients. Considering the radiation dose to the patient, it was not possible to do the comparison on the same patient. And because of the small number of MRI examinations in this series, we did not compare the performance between DEsCT imaging and MRI. Multi-modality studies should be done in the future. Finally, our readers assessed images in consensus, thus we do not have data on intra- or inter-observer variability. In conclusion, DEsCT imaging provides multiple types of images such as monochromatic images and material density images from a single acquisition. With the combination of the different images DEsCT improved the performance of preoperative diagnosis for insulinomas compared with conventional MDCT.
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Fig. 4. 41-Year-old man with a 18 mm insulinoma in the uncinate of pancreatic head. (A) Iodine density image in arterial phase did not show lesion clearly. (B and C) Optimal contrast to noise ratio (CNR) analysis based on default monochromatic image at 70 keV. (D) Optimal monochromatic image at 68 keV showed focally hypo-attenuation in the uncinate (white arrow). (E) Iodine density image in portal venous phase did not show the lesion clearly.
Conflict of interest One of the authors (Jian Ying Li) is the employee of General Electricity Healthcare. He provided technique assistance of spectral imaging and language support for the manuscript. He did not influence the result of this study and the other authors had the control over the data of this study. There are no potential conflicts of interest on the work under consideration for publication. Role of the funding source A funding was received for this work from Science and Technology Commission of Shanghai Municipality (10411953000). Acknowledgements The authors thank Dr. Celso Matos from Erasme Hospital, University Clinics of Brussels, Belgium, for the critical reading of the manuscript. The authors also thank Dr. Xiao-Hua Jiang and Dr. Jie
Cai, from the department of endocrinology Ruijin Hospital, for their clinical assistance.
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Dual energy spectral CT imaging of insulinoma—Value in preoperative diagnosis compared with conventional multi-detector CT Xiao Zhu Lin a,∗,1 , Zhi Yuan Wu a,1,2 , Ran Tao b,3 , Yan Guo c,4 , Jian Ying Li d,5 , Jing Zhang a,2 , Ke Min Chen a,6 a
Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197, 2nd Ruijin Road, Shanghai 200025, China Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197, 2nd Ruijin Road, Shanghai 200025, China Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197, 2nd Ruijin Road, Shanghai 200025, China d General Electricity CT Research Center, 1 Yongchang North Road Beijing Economic and Technologic Development Area, Beijing 100176, China b c
a r t i c l e
i n f o
Article history: Received 22 August 2011 Received in revised form 23 October 2011 Accepted 26 October 2011 Keywords: Insulinoma Spectral CT imaging Multi-detector CT Diagnosis
a b s t r a c t Objective: The aim of this study was to investigate the value of dual energy spectral CT (DEsCT) imaging in preoperative diagnosis of insulinomas in comparison with conventional multi-detector CT (MDCT). Materials and methods: Thirty-five patients were included in this study with 14 underwent the conventional dual-phase CT imaging (from March 2009 to January 2010) and 21 underwent the dual-phase DEsCT imaging (from February 2010 to May 2011). CT images were interpreted prospectively by two radiologists in consensus before operation. All the patients had diagnosis confirmed pathologically. The accuracy of preoperative diagnosis of insulinomas between DEsCT imaging and conventional MDCT, and between different kinds of images of DEsCT was compared. Results: There were 39 confirmed lesions among the 35 patients (23 and 16 tumors in the spectral CT group and MDCT group, respectively). MDCT detected 11 of 16 tumors. DEsCT imaging detected 20 of 23 tumors separately with the monochromatic image or the iodine density image, and 22 of 23 tumors with the combination of the two kinds of images. The sensitivity for the preoperative diagnosis of insulinoma was 95.7% with the combination of monochromatic and iodine density images in DEsCT imaging, statistically higher than that with the conventional MDCT (68.8%) (p = 0.033). Conclusion: Dual energy spectral CT imaging has higher sensitivity in preoperative diagnosis of insulinomas compared with conventional MDCT. The combination of monochromatic image and iodine density image can improve the diagnostic sensitivity of insulinomas. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Fasting hypoglycemia in healthy, well nourished adults is rare and is most commonly due to an adenoma of the islet of Langerhans, called insulinoma. Insulinomas are challenging lesions, difficult to
∗ Corresponding author. Tel.: +86 13764236797; fax: +86 2164661351. E-mail addresses: lin xiaozhu [email protected] (X.Z. Lin), [email protected] (Z.Y. Wu), [email protected] (R. Tao), [email protected] (Y. Guo), [email protected] (J.Y. Li), [email protected] (J. Zhang), [email protected] (K.M. Chen). 1 These authors contributed equally. 2 Tel.: +86 13564620606. 3 Tel.: +86 13301919116. 4 Tel.: +86 13918548754. 5 Tel.: +86 13910081465. 6 Tel.: +86 13701769751. 0720-048X/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2011.10.028
diagnose. Although insulinomas are very rare tumors, they are the most common functioning pancreatic endocrine tumors. The incidence in general population is 1–4 per 1,000,000 yearly but the incidence is higher in autopsy studies (0.8–10%) [1]. Insulinomas are usually small (1–2 cm) and can be difficult to localize; thus preoperative localization is key to successful surgical management. Due to the potent nature of insulin, even a tumor that is too small to localize with conventional imaging modality can produce debilitating and even life-threatening symptoms such as severe hypoglycemia, which results in neurologic dysfunction and symptoms of neuroglycopenia: confusion, visual disturbances, loss of consciousness, seizures, or rarely focal neurologic deficits resembling stroke. Operative removal of the tumor is the mainstay of treatment, but is predicated on precise preoperative localization. Many diagnostic modalities have been reported for the localization of insulinoma and can be either invasive or non-invasive. Computed tomography (CT) is the first choice for imaging [2,3]. Technical
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Fig. 1. 29-Year-old man with an 8-mm insulinoma in the pancreatic head. (A) Monochromatic image with 70 keV in arterial phase did not show lesion clearly. (B) Iodine density image showed focally hyper-density in the pancreatic head (white arrow). (C and D) Optimal contrast to noise ratio (CNR) analysis based on iodine density image. (E) Optimal monochromatic image at 49 keV showed focally hyper-attenuation in the pancreatic head (white arrow).
advances have led to the improvement in the quality of CT in terms of scan speed, coverage and spatial resolution. Studies with retrospective method have suggested improved performance for the detection of insulinomas with sensitivity from 83% to 94% [4–6] while the prospective detection rate is still very low, and was 63% in one of the studies [4]. Dual energy CT using dual tube voltages with either two consecutive scans or dual X-ray source-dual detector assembly has existed for a number of years to provide additional information for material separation with imaging [7–11]. Recently a dual energy spectral CT (DEsCT) imaging mode based on the rapid switching between highand low-energy data sets from view to view was introduced to produce both the material decomposition images and monochromatic spectral images. This scanning method has also found its use in several clinical applications including image quality improvement, diagnosis of pulmonary embolism, and differentiated diagnosis of hyper-vascular hepatic lesions [12–15]. In this study we investigated the clinical values of DEsCT imaging, a new technique for pancreatic imaging, for detection of insulinomas. The purpose of
this study was to evaluate the sensitivity of preoperative diagnosis of insulinoma with DEsCT imaging compared with a conventional multi-detector CT (MDCT).
2. Materials and methods 2.1. Patients This is a small sample single center study. All the patients were diagnosed and treated in our hospital. This study was approved by our institutional ethics committee. For the DEsCT imaging group (group 1), from February 2010 to May 2011, 21 patients [8 men, 13 women; median age 47 (13–81 years)] underwent dual-phase CT scans on a High Definition CT system (Discovery CT750HD, GE Healthcare, Milwaukee, Wisconsin, USA) with dual energy spectral imaging mode. The duration of symptoms (repeated episodes of hypoglycemia) of the 21 patients was from 3 months to 12 years (median time 2.75 years).
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For the MDCT group (group 2), clinical information of 14 patients [3 men, 11 women; median age 49 (26–71 years)] with insulinomas who had undergone conventional dual-phase CT scans from March 2009 to January 2010 on a 64-detector CT scanner (LightSpeed VCT, GE Healthcare, Milwaukee, Wisconsin, USA) were retrospectively reviewed. The duration of symptoms (repeated episodes of hypoglycemia) of these 14 patients was from 1 week to 16 years (median time 4.5 years). All the patients were operated after the diagnosis. The final diagnosis of insulinoma was made by histopathological examinations. 2.2. CT scans 1000 ml water was given over 15–20 min before the scanning. All patients were scanned craniocaudally in supine position. Unenhanced scans were acquired following scout scans with the conventional helical scan mode at 120 kVp tube voltage. Other parameters for the unenhanced scan include: collimation thickness 0.625 mm × 64, rotation time 0.6 s, pitch 0.984, auto mA with noise index 12. The unenhanced CT acquisition was used to localize the pancreas. Patients were then injected nonionic contrast medium (Iopamidol Injection, Iopamiro 300; Shanghai BRACCO Sine Pharmaceutical Corp. Ltd., China) via antecubital venous access by using a power injector (Ulrich medical, Germany) at a rate of 3–4 ml/s for a total of 80–100 ml during the arterial (AP) and portal venous phase (PP). The scanning delay for AP imaging was determined using a semi-automatic scan-triggering software (SmartPrep; GE Healthcare). AP scanning began 8 s after the trigger attenuation threshold (80HU) was reached at the level of the supra-celiac abdominal aorta. For the PP, the delay was 30 s after the end of AP. The acquisition of AP covered the whole pancreas and the acquisition of PP included the entire liver and pancreas. For group 1, both AP and PP were scanned with dual energy spectral imaging mode with fast tube voltage switching between 80 kVp and 140 kVp on adjacent views during a single rotation. Other scanning parameters were as following: collimation thickness: 0.625 mm × 64, SFOV: 50 cm, tube current: 600 mA, rotation speed: 0.6 s, helical pitch: 0.983. CTDIvol for the spectral CT mode was 21.8 mGy. Images were reconstructed with projection-based material decomposition software and a standard recon kernel. Waterand iodine-based material decomposition images and monochromatic images at energy levels ranging from 40 keV to 140 keV (with default level at 70 keV) were reconstructed from DEsCT acquisition. All images were reconstructed with 2.5 mm slice thickness. For group 2, the scanning parameters were as following: helical mode, collimation thickness: 0.625 mm × 64, SFOV: 50 cm, kV: 120 kVp, tube current: 250–550 mA, rotation speed: 0.8 s, helical pitch: 0.984. CTDIw values for this scan mode were from 12.0 mGy to 36.9 mGy. The average CTDI value for this group patients with conventional helical scanning was 20.1 mGy (±6.0 mGy), similar to that in the spectral CT mode. Images were reconstructed with a standard recon kernel, slice thickness 2.5 mm. 2.3. Image analysis CT images were interpreted prospectively for both groups by two radiologists (with 5 and 15 years of experience of abdominal imaging, respectively) before operation. The two radiologists recorded the lesion number, location [head (including uncinate process), neck, body, tail of pancreas] and size (the largest dimension) and made the final diagnosis by consensus. For group 1: the dual energy spectral image sets (iodine-based material decomposition images and the 101 sets of monochromatic images) were loaded on an advanced workstation (AW4.4; GE Healthcare, Waukesha, Wisconsin, USA) with the Gemstone Spectral Imaging viewer (GSI viewer, GE Healthcare, Waukesha,
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Wisconsin). GSI viewer allows the review of both the monochromatic energy images at a user selectable energy level for anatomic analysis, and the iodine-based material decomposition images for the quantitative iodine concentration analysis. The default monochromatic images (at 70 keV) and iodine-based material decomposition images were reviewed independently first and then combined for the initial reading. If any unusual enhancement in the pancreas was noted, using the lesion location determined on either image, the contrast-to-noise ratio (CNR) was calculated for the lesion with the region-of-interest (ROI) on the potential lesion and the normal pancreas parenchyma as background. The GSI viewer software package automatically propagated the CNR measurements for the 101 sets of monochromatic images and displayed the CNR values as function of photon energies. From the CNR-energy level plot, the optimal single energy (keV) level for generating the best CNR between the pancreatic lesion and the pancreas parenchyma was selected and the final imaging diagnosis was made on the monochromatic images with the optimal energy level (Fig. 1). For group 2: the conventional CT images (from MDCT) were interpreted through the Picture Archiving & Communication System in our hospital. 2.4. Statistical analyses The data was analyzed using SPSS13 (Chicago, IL, USA). Quantitative values were recorded as mean ± standard deviation for the size of tumor or median ± interquartile range for the age, duration of symptoms, time between CT scan and operation. The statistical significance level was set at 0.05. Independent sample tests were used for comparing the tumor size (t-test), age, duration of symptoms and time between CT scan and operation (Mann–Whitney test) between two groups. Chi-square test (Fisher’s exact) was used to compare the gender composition and tumor location between two groups. Chi-square test (Fisher’s exact) was used to compare the sensitivity of preoperative detection of insulinomas between the conventional MDCT and spectral CT imaging, and between different kinds of images of spectral CT. 3. Results During the study period, all the patients were underwent surgical resection [16 enucleation, 14 distal pancreatectomy (+/− splenectomy), 2 middle segmental pancreatic resection, 2 pancreatic head resection (+/− duodenum-preserving), and 1 laparoscopic distal pancreatectomy]. The median time between the CT scan and operation was 15 days (range 2–30 days) for group 1 and 7 days (range 3–25 days) for group 2. There were no significant differences on the patient age, gender composition, duration of symptoms, time between CT scan and operation between two groups (Table 1). Tumor samples were obtained by resection. The size of each tumor and the number of tumors were recorded. Twenty-three tumors in group 1 (21 patients, two patients had two lesions) and 16 tumors in group 2 (14 patients, one patient had 3 lesions) were identified by histopathological diagnosis. In group 1 ten tumors located in pancreatic head and neck, 12 in body and tail, and one tumor was exophytic (from uncinate process). In group 2 seven tumors located in pancreatic head and neck, 8 in body and tail, and one tumor was ectopic (below uncinate process). The average tumor size was 1.2 ± 0.5 cm (0.5–2.0 cm) for group 1 and 1.5 ± 0.5 cm (0.6–2.5 cm) for group 2 patients. There were no significant differences on tumor size, tumor location between two groups (Table 2). In group 1 with the dual energy spectral imaging, the optimal energy levels based on CNR measurement for pancreatic tumors were in the 45–60 keV range. The monochromatic image at the
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Table 1 Comparison of general information of the patients between two groups. Group
N
Sex
Age (y)[M ± (Q3 − Q1 )]
T1 (y)[M ± (Q3 − Q1 )]
T2 (day)[M ± (Q3 − Q1 )]
Spectral CT MDCT
21 14
8m:13f 3m:11f
47 ± 21 49 ± 22
2.5 ± 4.0 4.5 ± 4.0
15 ± 11 7±9
2 = 1.083 0.461
Z = −0.101 0.919
Z = −1.180 0.238
Z = −1.670 0.095
P
N: number of cases, m: male, f: female, y: year, M: median, Q3 − Q1 : interquartile range, T1: duration of symptoms, T2: time between CT scan and operation, 2 : Chi-square, Fisher’s exact, Z: Mann–Whitney test.
Table 2 The comparison of the tumors and the detection rate of tumors between two groups. Group
N
Location
Size (cm)
Sensitivity
a
23 16
10h–n:12b–t:1 exo 7h–n:8b–t:1ect
1.2 ± 0.5 1.5 ± 0.5
95.7%(22/23) 68.8%(11/16)
2 = 0.385 1.000
t = −1.502 0.142
2 = 5.246 0.033
Spectral CT MDCT P
a Spectral CT with combination of monochromatic image and iodine density image; N: number of tumors, h–n: head and neck, b–t: body and tail, exo: exophytic, ect: ectopic, 2 : Chi-square, Fisher’s exact, t: two sample independent t-test.
Table 3 The detection rate of insulinoma on different kinds of image sets.
Sensitivity
MDCT
Mono
Iodine
Mono + iodine
68.8%(11/16)
87.0%(20/23)
87.0(20/23)
95.7%(22/23)
= 1.918 0.235
= 1.918 0.235
2 = 5.246 0.033
2
2
P
MDCT: multidetector CT; mono: default monochromatic image with energy level at 70 keV; iodine: iodine density image; mono + iodine: monochromatic images combined with iodine density images; P: Chi-square test between MDCT image and spectral CT image (monochromatic image, iodine density image, monochromatic images combined with iodine density images).
optimal energy level alone detected 20 of 23 tumors (87.0%), and the iodine density image detected 20 of 23 tumors (87.0%). With the combination of both the monochromatic and iodine density image sets spectral CT imaging detected 22 of 23 tumors (95.7%). In group 2, the conventional MDCT detected 11 of 16 tumors (68.8%) (Table 3). There was no significant difference between monochromatic image and iodine density image on the detection rate (p = 1.000). Even though the detection rates with either the monochromatic image (87.0%) or the iodine density image (87.0%) independently were higher than that of the conventional MDCT (68.8%), they were not statistically significant (p = 0.235). However, there was significant difference for the sensitivity for preoperative diagnosis of insulinoma between DEsCT imaging with the two image sets combined and the conventional MDCT (p = 0.033, 2 = 5.246) (Table 3). In group 1, the conventional MDCT missed 5 insulinomas: 10mm insulinoma in the body and tail, three insulinomas (with size 12 mm, 15 mm, and 6 mm) in the pancreatic head, and one 15-mm insulinoma ectopic which was below the uncinate process of the pancreas. Among these tumors, one tumor was too small (6 mm) to be detected either by CT or by MRI, one tumor was ectopic and moderately enhanced, and the other three tumors had the enhancement similar to the pancreatic parenchyma with the 120 kVp polychromatic X-ray source which had an average energy of about 70 keV for the patients. Two of the five tumors could be confirmed retrospectively. Three of the 5 tumors were detected by MRI, and one of the patients was diagnosed by selective arterial calcium stimulation and hepatic venous sampling before the surgery (Fig. 2). The patient with a 6 mm lesion missed had another 20 mm lesion and thus been operated. In group 2, the use of monochromatic image alone initially missed three tumors: two tumors in the pancreatic head (with size 8 mm and 5 mm), and one 6 mm insulinoma in the pancreatic tail. The two tumors in the pancreatic head were iso-attenuating to the pancreas on monochromatic image with the default 70 keV
energy level, but they were hyper-dense on the iodine images and the optimal monochromatic images with 40 keV and 49 keV (Fig. 3). The tumor in the pancreatic tail could not been found either on the monochromatic images or on the iodine images. The other two tumors missed by iodine images had hypo-density: 20 mm insulinomas in the body and tail, and 18 mm insulinoma in the uncinate process. The monochromatic images detected these two hypo-attenuation tumors (Fig. 4). 4. Discussion The sensitivity for preoperative detection of insulinomas with the dual energy spectral CT imaging using both the material decomposition images and monochromatic images generated from the single acquisition was 95.7% (22/23), which was higher than that of conventional MDCT (68.8%, 11/16) in this study and was also higher than the results of previous studies [3–6,16]. In this study, the conventional MDCT missed 5 insulinomas. Two of the five tumors could be confirmed retrospectively. Three of the 5 tumors were detected by MRI, and one of the patients was diagnosed by selective arterial calcium stimulation and hepatic venous sampling before the surgery (Fig. 2). For the DEsCT, the use of monochromatic image alone initially missed three tumors. Two of the three tumors were iso-attenuating to the pancreas on monochromatic image with the default 70 keV energy level, but with the adjustment of energy levels for the monochromatic image sets from the default 70 keV to the optimal ones, these two tumors were detected (Fig. 3). One of the three tumors could not been found either on the monochromatic images or on the iodine images. It might be too small and iso-attenuating. Two tumors missed by iodine images had hypo-density, and the monochromatic images detected these two hypo-attenuation tumors. It might because of the lower image noise and higher CNR of the monochromatic image compared to the iodine images. Therefore, with the combination of
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Fig. 2. 37-Year-old woman with a 10-mm insulinoma in the junction of pancreatic body and tail. (A and B) Conventional MDCT image in arterial phase and portal venous phase showed iso-attenuation lesion in the junction of pancreatic body and tail. (C–F) MRI images of the same patient. T2 weighted image showed hyper-intensity lesion (C), T1 weighted image with fat suppression showed hypo-intensity lesion (D), T1 weighted image in arterial phase showed iso-intensity lesion (E), and T1 weighted image in portal venous phase showed iso-intensity lesion (F) in the junction of pancreatic body and tail.
the monochromatic image and iodine image, the insulinomas with uncommon characteristic such as iso- or hypo-attenuation could also be detected successfully. This can improve the sensitivity of preoperative diagnosis for the insulinomas. The averaging attenuation effect of polychromatic X-rays in conventional CT imaging reduces the low-contrast resolution between materials. In addition, beam hardening caused by the preferential absorption can shift the HU value for a material within the scan field of view of a patient or between patients. Because of beam hardening artifacts, CT numbers are sometimes unreliable for enhancing/nonenhancing verification in small lesions. On the other hand, spectral CT imaging provides the monochromatic images depicting how the imaged object would look if the X-ray source produced only single energy X-ray photons. This would allow for eliminating the beam hardening artifacts and averaging attenuation effects [12], as well as for increasing contrast resolution. According to the density of the lesion and the background, GSI viewer could provide an optimized energy level and on the optimal monochromatic images the lesion was displayed with the best CNR which further improved the lesion detection rate [13]. Because of the scanner limitation we did not compare the monochromatic images obtained with fast-switching technique with that of dual-source method where images from the
two tube-detector assemblies were reconstructed individually and then combined with different weights. However, it was pointed out by previous researchers that the monochromatic images generated from the raw-data reconstructed may be superior to the imagebased method in terms of less susceptible to the beam hardening artifacts [17,18]. For medical diagnostic imaging, water and iodine are often selected as the basis pair for material decomposition image presentation because their atomic numbers span the range of atomic numbers for materials generally found in medical imaging and approximate those of soft tissue and iodinated contrast material to result in material-attenuation images that are intuitive to interpret. For the small hypervascular lesions such as insulinoma, small hepatocellular carcinoma and small hepatic hemangioma, iodine density image could be very sensitive, showing focal uptake of the iodinated contrast material [14]. And the small lesion could be isoattenuation on the conventional CT images because of the averaging attenuation effect of polychromatic X-rays. Multiple imaging options are available for preoperative localization of insulinomas, including trans-abdominal ultrasound, CT, MRI, endoscopic ultrasound (EUS), and angiography with intraarterial calcium stimulation testing [19,20]. The availability and
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Fig. 3. 53-Year-old woman with an 8 mm insulinoma in the pancreatic head. (A) Monochromatic image with 70 keV in arterial phase did not show lesion clearly. (B) Iodine density image showed focally hyper-density in the pancreatic head (white arrow). (C) Optimal monochromatic image at 40 keV showed focally hyper-attenuation in the pancreatic head (white arrow). (D) Monochromatic image with 70 keV in portal venous phase did not show lesion clearly. (E) Iodine density image showed slightly focal hyper-density in the pancreatic head (white arrow). (F) Optimal monochromatic image at 49 keV showed slightly hyper-attenuation in the pancreatic head (white arrow).
success rates of imaging and localization techniques vary between institutions. Improvements in MDCT technology have allowed optimization of the scanning protocols with rapid scan times, which reduces movement artifacts and allows accurate contrast medium bolus tracking. This ensures optimal timing of the scan and excellent arterial-phase images and permits image reconstruction in thinner slices, which results in improved image resolution and the sensitivity of preoperative detection [21]. Some of the previous studies have demonstrated that MRI is superior to other preoperative imaging techniques in identifying small pancreatic insulinomas [22]. Its sensitivity ranges from 71% to 95% in the detection of insulinomas and the determination of the presence of metastases [16,22–24]. The main limitation of MRI is that the quality of the examination seriously depends on the cooperation of the patients, especially for the detection of small lesions. In this study, only 13 patients with 15 lesions (65.2%, 15/23) had MRI in the group of DEsCT imaging. In the prospective diagnosis, MRI missed 7 lesions (sensitivity: 53.3%, 8/15). During the retrospective review of the images, two more lesions were confirmed with the sensitivity of 66.7%, which is similar to conventional MDCT while lower than DEsCT in this study. EUS can also provide useful information about tumor size and proximity to surrounding structures, but it requires operator expertise in both advanced
endoscopy and ultrasound. We had very limited experience with EUS for insulinomas, even though it was reported to have higher sensitivity (75–89%) than either CT scan or abdominal ultrasound in identifying small tumors as reported in the previous studies [16,24]. However, like traditional trans-abdominal US, the images obtained are typically less helpful to the operating surgeon. Our study does have some caveats. First, this investigation reflects our preliminary experience in a small number of patients. Larger sample study needs to be performed to validate our results. Second, in this study we compared DEsCT imaging and conventional MDCT with different groups of patients. Considering the radiation dose to the patient, it was not possible to do the comparison on the same patient. And because of the small number of MRI examinations in this series, we did not compare the performance between DEsCT imaging and MRI. Multi-modality studies should be done in the future. Finally, our readers assessed images in consensus, thus we do not have data on intra- or inter-observer variability. In conclusion, DEsCT imaging provides multiple types of images such as monochromatic images and material density images from a single acquisition. With the combination of the different images DEsCT improved the performance of preoperative diagnosis for insulinomas compared with conventional MDCT.
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Fig. 4. 41-Year-old man with a 18 mm insulinoma in the uncinate of pancreatic head. (A) Iodine density image in arterial phase did not show lesion clearly. (B and C) Optimal contrast to noise ratio (CNR) analysis based on default monochromatic image at 70 keV. (D) Optimal monochromatic image at 68 keV showed focally hypo-attenuation in the uncinate (white arrow). (E) Iodine density image in portal venous phase did not show the lesion clearly.
Conflict of interest One of the authors (Jian Ying Li) is the employee of General Electricity Healthcare. He provided technique assistance of spectral imaging and language support for the manuscript. He did not influence the result of this study and the other authors had the control over the data of this study. There are no potential conflicts of interest on the work under consideration for publication. Role of the funding source A funding was received for this work from Science and Technology Commission of Shanghai Municipality (10411953000). Acknowledgements The authors thank Dr. Celso Matos from Erasme Hospital, University Clinics of Brussels, Belgium, for the critical reading of the manuscript. The authors also thank Dr. Xiao-Hua Jiang and Dr. Jie
Cai, from the department of endocrinology Ruijin Hospital, for their clinical assistance.
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