The present study obtained approval from the ethics committee of our hospital, and all patients signed the informed consent after a full explanation of the nature of the study. 90consecutive patients with primary CRC were enrolled from May 2015 to March 2019. Inclusion criteria: (1) Patients were confirmed as CRC by biopsy. (2) Patients did not receive radiotherapy or chemotherapy before surgery. (3) Patients had no iodine allergic history and no symptoms of hyperthyroidism. From these, 19 cases were excluded due to the following reasons: (1) poor preparation of bowel(n=7), (2) poor intestinal filling (n=5), (3) metal artifacts caused by pelvic or lumbar surgery (n=3), and (4) presence of gas artifacts affecting observation (n=4). Ultimately, a total of 71 cases were included in this study, including 41 males and 30 females, aged 31-91 years, with a mean age of (59.3±14.1) years. Patients underwent dual-phasic contrast-enhanced DECT 1-3 days before surgery.
The day before the examination, the patients were given a light diet that does not easily produce gas and dregs. In the morning on the day of DECT examination, patients underwent cleansing enema in the ward until the watery stool discharged. 400 ml~1000 ml warm water (according to the tolerance of patients) was injected into the rectum before scanning.
All examinations were performed using a single-source CT system (Aquilion ONE; Canon Medical Systems), equipped with 320-detector raw and covered 160 mm in the z-direction. This system is capable of rapidly switching tube voltage from 80 to 135 kV within 50 milliseconds and automatically adapting the corresponding tube current. All patients were scanned in the supine position and underwent a routine non-contrast CT scan with the scanning parameters (tube voltage of 140 kV, tube current of 112~187 mA, matrix of 512×512, FOV of 240 mm, the rotation speed of 0.35 s/rot, slice thickness of 0.5 mm, slice spacing of 0.5 mm, and the scanning scope ranged from the diaphragmatic dome to pubic symphysis). The dual-phasic contrast-enhanced scans were then performed using the dual energy mode. The scan parameters were as follows: matrix of512×512, FOV of 240 mm, the rotation speed of0.35 s/rot and slice thickness of 0.5 mm, volume scan.55-86 ml (1.0 ml/kg) of a nonionic iodinated contrast agent (Ultravist300; Schering) was then administered via the antecubital vein at a flow rate of3 ml/s by G22 needle through an automatic injector. The dual-phasic scans were obtained at 40 s (arterial phase) and 70 s (venous phase) centering the tumor after the start of the contrast injection, respectively. The third generation AIDR 3D iterative algorithm developed by Canon was used, and the effective dose was 5.39 ± 0.48 mSv.
After surgical resection of the colorectal tumor, each specimen was taken back to the department of radiology and again imaged using the same conventional non-contrast sequence in the coronal and transverse planes before the specimen was fixed with formalin. After scanning, the specimens were immediately fixed with 4% neutral formaldehyde and delivered for the pathological examination.
The image slices of the preoperative CT scan and the postoperative specimens were compared to locate and mark all correct topographical matching lymph nodes with a diameter greater than 4mm in a blinded fashion by two radiologists (L.Q. and X.R.C., with 9 and20years abdominal imaging experience, respectively) in consensus. The morphological features of each lymph node were recorded according to the CT characteristics, ie, short-axis diameter, shape, border, and density. Subsequently, the specimens were delivered to the Department of Pathology, where every marked lymph node was harvested by one radiologist (L.Q) and one pathologist (Z.P.W., with 10 years of experience in pathological diagnosis). Any mismatch found between specimen CT images and histological findings were recorded and excluded from the study. Finally, all good-matched lymph nodes were stained with hematoxylin & eosin and were placed under a microscope for observation of histological features by two pathologists (Z.P.W. and G.Y.J., with 20 years of experience in pathological diagnosis), so as to determine the presence of tumor deposit.
The dual-phasic image volumes were loaded into the DE postprocessing software in the display console (Canon Aquilion ONE, Canon Medical System). The DE software automatically generated 35~135Kev CT values to form single-energy CT curve, dual-energy iodine, base material, electron density and atom number images. A region of interest (ROI) of 12~78 mm2was drawn using a circular tool on each marked lymph node on the reconstructed 69-keV monochromatic images (Fig.1). ROI was chosen to cover the nodal parenchyma as large as possible. The obvious suspicious necrotic region or fatty hilum was avoided from the ROI to minimize the influence of potential errors. Each lymph node was measured thrice and a mean value was calculated. Another ROI was placed on the right iliac artery at the corresponding layer as a reference. All of the ROIs were automatically copied onto all dual-energy iodine, base material, electron density and atom number images to calculate iodine concentration value (△HU), iodine water ratio value (IWR), electron density value (ρeff) and atom number value (Z).Measurements were performed in a blinded fashion by another two independent radiologists (J.J.H. and S.R.L., with 3 and 32years abdominal imaging experience, respectively) .
The slope of the dual-energy curve was expressed as λHu, which was calculated by λHU=（35KeV HU－ 69KeV HU）/34 KeV, where 35KeV HU and 69KeV HU were the CT values at 35 KeV and 69 KeV, respectively (Fig. 2). The △HU, IWR, ρeff and Z values of lymph nodes were normalized to values in the iliac artery to drive the normalized values: n△HU=△HUtissue/△HUartery, nIWR=IWRtissue/IWRartery, nρeff=ρefftissue/ρeffartery, and nZ=Ztissue/Zartery. The measurements were carried out separately by two observers, and the average values were obtained for statistical analysis.
Statistical analyses were performed using SPSS20.0 (IBM, Aromonk) and Medcalc (MedCalc Software, Acacialaan 22, B-8400) software. A difference with P<0.05 was considered statistically significant. Measurement data in accordance with normal distribution were expressed by . Bland-Altman plots and the intraclass correlation coefficient (ICC) were used to analyze the interobserver variability of λHU, n△HU, nIWR, nρeff and nZ values: poor (less than 0.40), fair (0.40–0.59), good (0.60– 0.74), and excellent (0.75–1.00). The DECT parameters for the non-metastatic and metastatic lymph nodes were analyzed separately using two-sample t test. And the DECT parameters with statistical significance were used to plot receiver operating characteristic (ROC) curves, in which the optimal cut-off values were obtained using the Maximum Youden’s index method.