Introduction
Contrast-enhanced ultrasonography is a dynamic imaging technique for assessing tissue perfusion after contrast agent injection.1,2 Contrast agents consist of gas-filled microbubbles encapsulated by a shell that resonate when exposed to an ultrasound beam, reflecting the blood perfusion of an organ as increased pixel intensity due to harmonic signaling.3,4 The tissue perfusion of an organ can be assessed in real time with contrast enhancement by evaluating the timing of the wash-in and washout phases.4,5 Further, quantitative CEUS parameters such as PI, TPE, AUC, and wash-in rate can be obtained through TIC analysis and aid in the diagnosis and monitoring of diseases.6
Various contrast agents are available for ultra-sonography according to the type of gas and type of encapsulated shell of the microbubble.7 One such example, SHM, has a phospholipid peripheral shell. Its half-life after IV injection is 6 minutes, and > 80% of the agent is eliminated through the lungs after 11 minutes.1 Another contrast agent, PFB, consists of a lipid-stabilized suspension of PFB within a hydrogenated egg phosphatidylserine shell. It is eliminated through phagocytosis by liver Kupffer cell and has a half-life of 30 to 45 minutes.1
The microbubbles of contrast agents resonate with appropriate acoustic power of the ultrasound beam, which is represented by the MI, a unitless ultrasound parameter.8,9 The degree of microbubble destruction relies on the resistance of the encapsulated shell and the MI. Use of the appropriate MI for the contrast agent is important for obtaining a strong nonlinear response from microbubbles and for ensuring sufficient examination time via an adequate life span of the contrast agent.9 Too high an MI can disrupt microbubbles, whereas too low an MI can result in poor visualization of the far field.
Both SHM and PFB are generally used with low-MI (< 0.5) beams to avoid—or at least minimize— microbubble destruction in CEUS examinations.8–10 Within the low-MI range, PFB is typically used at a higher MI than SHM is; a study11 in rabbits revealed that the maximum PI of the liver was produced at an MI of 0.15 for SHM and 0.4 for PFB. In people, PFB was found to be more sensitive for detecting microbubbles in healthy liver at a higher versus lower MI.12 In general, because attenuation of an ultrasound beam is decreased at a high MI, the detection of lesions that are deep within the abdomen can be improved. Although PFB might produce superior, more sensitive diagnostic images than SHM does, few reports exist of direct evaluation of the signal intensity, image quality, and detectability of different contrast agents used at different MI settings.
Perfusion of the pancreas is important in many pathological conditions such as severe pancreatitis and pancreatic tumors. Although measurement of pancreatic lipase immunoreactivity combined with ultrasonographic examination of the pancreas is recommended for diagnosis of pancreatitis in dogs, it is challenging to detect ischemic changes and predict the induction of pancreatic necrosis in severe pancreatitis because the sensitivity of conventional ultra-sonography for pancreatic necrosis is only 53.3%.13,14 Furthermore, perfusion assessments can be useful for distinguishing insulinoma on the basis of the hyper-vascular nature of the tumor.15–17
The CEUS features of the pancreas in dogs have been investigated in a few studies. In 2 studies,15,16 both PFB and SHM helped to demarcate pancreatic nodules and masses and allowed detection of a hyperechoic insulinoma at the early phase after contrast agent injection. In addition, SHM can facilitate differentiation of insulinoma from pancreatic adenocarcinoma in dogs.16 Perfluorobutane produces a delayed higher peak with prolonged hyperechoic enhancement of the pancreas in dogs with naturally occurring pancreatitis and cerulean-induced acute pancreatitis.18,19 However, performance of CEUS with perflutren lipid microspheres produces an increase in PI and shortening of the TPE in dogs with versus without pancreatitis.20 Some studies9,21–23 have compared the usefulness of various contrast agents for performance of CEUS. In humans, no significant difference was found in the diagnostic accuracy of SHM versus PFB for differentiating a focal malignant or benign mass in the liver.21,24 However, PFB was superior to SHM for identifying liver lesions at the parenchymal phase because its microbubbles are phagocyted by liver Kupffer cells, thus allowing parenchymaspecific imaging and more delayed scanning.24 To the authors' knowledge, no study has been reported comparing the diagnostic accuracy of SHM and PFB for CEUS of the pancreas.
The purpose of the study reported here was to compare SHM and PFB for performance of CEUS of the pancreas in healthy dogs and determine the optimal parameters for this purpose. We hypothesized that PFB would provide a higher PI and AUC and faster wash-in rate than would SHM because the use of PFB at a higher MI would allow for an improved detection response ratio. Further, we hypothesized that the TPE would be similar with both agents because it is determined by arterial blood flow per unit of blood volume. Moreover, TPE is not significantly influenced by the detection response, contrast agent stability, or MI.25
Materials and Methods
Animals
Eight purpose-bred Beagles (5 females and 3 males) were used in this crossover study. All dogs had no history of gastrointestinal disease or participation in research associated with the digestive system. Mean age was 2.9 years (range, 2 to 4 years), and mean body weight was 9.1 kg (range, 6.8 to 10.2 kg). All 8 dogs were deemed clinically normal by physical examination, CBC, serum biochemical analysis, serum canine pancreatic lipase immunoreactivity, serum electrolyte concentration analysis, abdominal radiography, and abdominal ultrasonography. Dogs were individually housed and provided with commercial dry food and tap water ad libitum.
Food was withheld from dogs for 24 hours prior to anesthesia for the study procedures. Abdominal radiography and ultrasonography were performed to confirm that dogs were unfed. Systolic arterial blood pressure was measured by the Doppler method before and after anesthesia.
The study protocol was approved by the Institutional Animal Care and Use Committee of Chonnam National University, Korea (protocol No. CNU IACUCYB-R-2020-2). Dogs were cared for in accordance with the Guidelines for Animal Experiments of Chonnam National University.
Ultrasonography
Anesthesia was induced in each dog by IV injection of alfaxalonea (3 mg/kg). An endotracheal tube was placed, and anesthesia was maintained with isofluraneb (2%) in oxygen (1 L/min). Hair was clipped over the entire ventral abdominal region, and dogs were positioned in left lateral recumbency. Conventional ultrasonography and CEUS were performed by use of an ultrasound machinec with a 10-MHz linear transducer. On conventional ultrasonography, the time gain control was set at its central position and the power was set at a constant level, with a gain of 64 dB. The pancreatic body was identified, with the portal vein as a landmark between the left and right pancreatic lobes on B-mode images. The left lobe was found caudal to the greater curvature of the stomach toward the spleen. The right lobe was found medial to the descending duodenum and caudal to the cau-date lobe of the liver. The pancreas was deemed to be normal when the pancreatic parenchyma was isoechoic or slightly hyperechoic to the liver and isoechoic or slightly hypoechoic to the surrounding mesentery. The pancreas in all dogs had a homogeneous echotexture. The normal size of the pancreas was 6 to 8 mm thick. The pancreatic duct was visualized as 2 thin hyperechoic lines with a pancreatic ductal diameter of 0.6 mm.26 No pancreatic edema or surrounding fat hyperechoic change was observed.
In each dog, CEUS of the pancreatic body was performed twice: once with SHMd (2.5 mg/dog) and once with PFB5 (0.015 mL/kg [0.12 mL microbubbles/ kg]), in random order (selected from a random number table) with at least 3 days between examinations. The person who performed the CEUS (SP) was not blinded to the type of contrast agent administered because, per the manufacturers of the agents, different ultrasonographic settings (eg, MI) were recommended for each. Each contrast agent was first agitated and then administered by rapid bolus injection into a cephalic vein through a 22-gauge catheter via 3-way stopcock, immediately followed by rapid bolus injection of 5 mL of saline (0.9% NaCl) solution.f Simultaneously, dynamic sequences were recorded from the beginning of the bolus injection to 120 seconds after injection, keeping the transducer at the same location on the pancreatic body. All CEUS examinations were performed in the extended pure harmonic detection mode, with the focus point set at the bottom for homogeneous energy distribution over the image. For SHM and PFB, respectively, the transmitted energy was reduced to magnitudes of 7% and 10%, and the MIs used were 0.07 and 0.22 in accordance with manufacturer recommendations.
Image analysis
The recorded cine images were qualitatively assessed on a 3-point scale for homogeneity of pancreatic enhancement and conspicuity of the pancreatic signal from the background on the ultrasound machine (Appendix). Homogeneity of pancreatic enhancement was evaluated as the percentage of the nonenhanced area in the pancreatic body at the wash-in phase after contrast agent injection. Heterogeneity caused by an intense signal from the pancreatic vessels was not considered in the evaluation. Wash-in phase was defined as the progressive enhancement within an ROI, specifically defined as the period from the arrival of microbubbles to peak enhancement. Washout phase was defined as the period of reduction in enhancement following peak enhancement. All qualitative assessments were performed by consensus agreement between 2 observers (SP and HJ).
For these assessments, all cine loops from CEUS examinations were evaluated with the aid of the installed software.g The CEUS images displayed the acoustic intensity (level) as a function of time. Circular ROIs with a diameter of 3 mm were placed over the pancreatic body in an effort to exclude vessels passing through the pancreatic parenchyma—as much as possible—from the ROIs; the TIC was then obtained. The locations of the ROIs were manually adjusted frame by frame to correct for altered motion due to respiration. Values for the CEUS parameters PI, TPE, AUC, and wash-in rate were obtained for each ROI. Peak intensity was measured as the highest signal value during the examination. Time to peak enhancement was measured as the time from the start of injection to PI. Area under the curve was defined as the integral of the signal intensity curve over time. Wash-in rate was defined as the maximum slope between the time of onset of contrast agent inflow and TPE. Signal value of background noise was measured as the signal value from each ROI just before the injection of contrast agents (at time 0).
After the CEUS procedures, the general condition of each dog, including appetite, rectal temperature, activity, and clinical signs (ie, vomiting, abdominal discomfort, or local injection site reaction), was monitored for 5 days.
Statistical analysis
Statistical analyses were performed with statistical softwareh by one of the authors (SP) under supervision of a statistician. Differences between the 2 contrast agents in homogeneity of pancreatic enhancement and conspicuity of the pancreatic signal from the background were evaluated with the Wilcoxon signed rank test. Values of quantitative parameters (PI, TPE, AUC, and wash-in rate) and background noise were compared between contrast agents with the paired t test. All data are reported as mean ± SD. Values of P < 0.05 were considered significant.
Results
On conventional ultrasonography, the body and lobes of the pancreas were observed as homogeneous, hypoechoic parenchyma with normal surrounding fat in all dogs. Performance of CEUS with SHM and PFB was successful in all dogs, and no adverse effects related to contrast agent injection or anesthesia were observed in any dog. Mean ± SD systolic arterial blood pressure before and after anesthesia was 134.17 ± 17.44 mm Hg when SHM was used and 111.67 ± 14.72 mm Hg when PFB was used.
With both contrast agents, each pancreas was rapidly enhanced in the wash-in phase, which occurred approximately 5 to 15 seconds after injection. Immediately after the PI was reached, an overall fast decrease of the pancreatic signal was observed during the wash-out phase which lasted 15 to 25 seconds. Subsequently, the signal intensity leveled out until the end of the examination. The homogeneity values for pancreatic enhancement with SHM (mean ± SD score, 2.6 ± 0.5) and PFB (2.8 ± 0.5) were not significantly (P = 0.56) different (Table 1). Acoustic shadows or reverberation artifacts caused by gas in the stomach or descending duodenum prevented visualization of focal regions of the pancreas. Most of the heterogeneities observed in dogs that received a homogeneity score of 2 were probably related to these artifacts. During the period between the wash-in and washout phases, the pancreases were more hyperechoic when enhanced with PFB versus SHM (Figure 1). The conspicuity of the pancreatic signal relative to the background was significantly (P = 0.03) higher with PFB enhancement (mean ± SD score, 3 ± 0) than with SHM enhancement (2.25 ± 0.7). Mean ± SD background noise for SHM and PFB was 28.49 ± 5.63 dB and 44.29 ± 9.50 dB, respectively.
Number of healthy adult Beagles (n = 8) with various scores for homogeneity of pancreatic enhancement and conspicuity of the pancreatic signal on CEUS images of the pancreas obtained with SHM (2.5 mg/dog, IV) and PFB (0.015 mL/ kg [0.12 mL of bubbles/kg], IV) as contrast agents in a crossover study design.
| Score | SHM | PFB |
|---|---|---|
| Homogeneity | ||
| 1 | 0 | 0 |
| 2 | 3 | 2 |
| 3 | 5 | 6 |
| Conspicuity | ||
| 1 | 1 | 0 |
| 2 | 4 | 0 |
| 3 | 3 | 8 |
Representative conventional ultrasonography images (A and B) of the pancreas in a healthy Beagle and CEUS images obtained with SHM (C) and PFB (D) as contrast agents. In each CEUS image, a circular ROI with a diameter of 3 mm is shown over the pancreatic body for quantitative analysis. The PI for PFB enhancement was higher than the PI for SHM enhancement. p = Pancreatic body.
Citation: American Journal of Veterinary Research 82, 7; 10.2460/ajvr.82.7.538
Representative conventional ultrasonography images (A and B) of the pancreas in a healthy Beagle and CEUS images obtained with SHM (C) and PFB (D) as contrast agents. In each CEUS image, a circular ROI with a diameter of 3 mm is shown over the pancreatic body for quantitative analysis. The PI for PFB enhancement was higher than the PI for SHM enhancement. p = Pancreatic body.
Citation: American Journal of Veterinary Research 82, 7; 10.2460/ajvr.82.7.538
Representative conventional ultrasonography images (A and B) of the pancreas in a healthy Beagle and CEUS images obtained with SHM (C) and PFB (D) as contrast agents. In each CEUS image, a circular ROI with a diameter of 3 mm is shown over the pancreatic body for quantitative analysis. The PI for PFB enhancement was higher than the PI for SHM enhancement. p = Pancreatic body.
Citation: American Journal of Veterinary Research 82, 7; 10.2460/ajvr.82.7.538
Both contrast agents demonstrated a similar TIC pattern after injection: an initial rapid upslope, a maintained plateau, and then a fast downslope. Results of quantitative assessment were summarized (Table 2). Mean values of PI, wash-in rate, AUC, and background noise were significantly higher with PFB enhancement than with SHM enhancement. There was no significant difference between contrast agents in TPE values.
Values of quantitative parameters for CEUS of the pancreas in the dogs of Table 1.
| Parameter | SHM | PFB | ||
|---|---|---|---|---|
| Mean ± SD | Range | Mean ± SD | Range | |
| PI (dB) | 53.95 ± 8.83a | 41.32–69.96 | 144.02 ± 6.63b | 131.69–150.96 |
| TPE (s) | 9.83 ± 0.80a | 8.9–11.03 | 10.21 ± 0.96a | 9.2–11.13 |
| Wash-in rate (dB/s) | 99.57 ± 17.32a | 82.86–127.62 | 212.67 ± 23.33b | 170.31–248.88 |
| AUC (dB X s) | 3,182.63 ± 418.94a | 2,654.32–3,968.96 | 8,281.29 ± 269.63b | 6,666.14–8,731.76 |
Within a row, values with different superscript letters differ significantly (P < 0.001).
Discussion
The CEUS features of the normal pancreas in dogs with SHM and PFB contrast enhancement were determined in the present study, and the homogeneity of the pancreas and conspicuity of the pancreatic signal relative to the background were qualitatively compared between the 2 agents. In addition, quantitative parameters, including PI, TPE, AUC, and wash-in rate, were compared. Both agents revealed a similar contrast enhancement pattern of the pancreas, providing rapid and homogeneous enhancement. However, the pancreatic enhancement obtained with PFB was more hyperechoic and more conspicuous than the pancreatic enhancement obtained with SHM. Values of PI, AUC, and wash-in rate with PFB enhancement were significantly higher than those with SHM. However, no significant difference was found for TPE.
Characteristics common to the 2 contrast agents were revealed when the pancreatic CEUS examination was observed in real time. Pancreases had homogeneous, rapid, intense enhancement within 5 to 15 seconds after injection of either contrast agent because the pancreas receives its blood supply entirely from arterial flow.25,27,28 Pancreatic enhancement was maintained constantly for < 5 seconds. Then, each pancreas had a rapid washout that appeared as hypoenhancement when compared with the nearby liver tissue.
Wash-in rate can differ with the vascularity of pancreatic lesions. Typically, insulinomas are hyper-vascular and show higher enhancement than normal pancreatic parenchyma does during the wash-in phase.28 Homogeneous enhancement of the pancreatic parenchyma is important for delineation of avascular pancreatic lesions such as nodules and ischemia.28 In the present study, 69% (11/16) of images showed entirely homogeneous enhancement, whereas the remaining 31% (5/16) showed partial homogeneous enhancement with total hypoenhanced area making up < 25% of the parenchyma. No difference in homogeneity was noted between SHM and PFB. No dog had homogeneous enhancement containing a total hypoenhanced area of > 25% of the parenchyma for either agent. The heterogeneity of the images that received a homogeneity score of 2 might have been confused with malignant nodules. However, most of the observed heterogeneities had sparsely scattered hypoechoic or hyperechoic signals, which were considered to have been caused by gas in the stomach or descending duodenum adjacent to the pancreas but not from the pancreas itself. For this reason, the dogs with a homogeneity score of 2 also had homogeneous enhancement on most of the area except for areas where the acoustic shadows or reverberation artifacts occurred. This gas-induced heterogeneity can be overcome by changing the posture of the patient when performing CEUS in clinical practice. Thus, the minor heterogeneities observed with SHM or PFB enhancement were not severe enough to be difficult to distinguish from pathological findings.
The PFB enhancement provided more conspicuous CEUS images of the pancreas, with more hyper-echoic pancreatic enhancement relative to the background when compared with SHM-enhanced images. In 5 of 8 dogs after SHM administration, the pancreatic enhancement was not significantly different from the background noise. The conspicuity of the pancreas after PFB enhancement can be determined both by the brightness relative to the background noise and by the signal intensity caused by microbubbles.29 As the MI increases, the noise artifact generated by the tissue response also increases.29 Because PFB was used at a higher MI than SHM was, more severe background noise was produced in PFB images. Nevertheless, PFB produced an overall much stronger signal than the background noise, which resulted in the observed high conspicuity. Mean background noise for SHM and PFB was 28.49 and 44.29 dB, respectively. During the wash-in phase of CEUS, the signal of the pancreatic parenchyma became distinguishable from the noise when the signal reached approximately 40 to 50 dB and 70 to 80 dB for SHM and PFB, respectively. The SHM produced relatively low PI values that ranged from 43.32 to 69.96 dB, representing an approximately 15- to 40-dB difference from the background noise, whereas PFB produced high PI values that ranged from 131.69 to 150.96 dB, representing an approximately 90- to 100-dB difference from background noise. These high PI values enabled all PFB images to achieve a conspicuity score of 3.
Because of the high conspicuity of PFB, the effect of the background noise was considered to be negligible when placing the ROIs for analysis, making it easy to obtain the ideal TIC on quantitative evaluation. On the other hand, because SHM demonstrated lower conspicuity, it was more difficult to obtain the ideal TIC when the noise signal was in the ROIs. The usefulness of SHM versus PFB for diagnosing focal liver lesions has been compared in humans, and both agents produced better image quality and improved diagnostic accuracy than conventional ultrasonography did.24 Given that a larger ROI can be placed on the liver versus the pancreas, the TIC might have been less affected by noise and thus more conducive to obtaining the ideal TIC regardless of the contrast agent. In the present study, ROIs with a 3-mm diameter were used because larger ROIs were not possible. One reason for that was that the mean width of the pancreatic body in dogs is approximately 3 cm; owing to difficulty in scanning the widest plane, the actual scanned plane of the pancreas in the present study was only 1 to 1.5 cm. Moreover, in some instances, either the ROI deviated from the pancreatic parenchyma or the pancreatic blood vessels entered into the ROI because of continuous movement of the dogs during breathing. Thus, conspicuity of the signal from the background noise was considered important when pancreatic CEUS was performed in this study. The PFB was more useful than SHM because of its high conspicuity score, which means an ability to produce images of a strong signal relative to the background noise.
In quantitative evaluations, the TIC represents the enhancement pattern of the pancreas. Although both contrast agents in the present study generated a similar TIC shape, the signal intensities generated by contrast enhancement for PFB were generally higher than those for SHM. The PI and AUC values were significantly higher when PFB versus SHM was used. This result was attributed to the greater stability of PFB, which is due to the properties of the micro-bubbles' response to acoustic energy; such stability enables PFB to obtain stronger signals with a higher MI.1,12,29 Time to peak enhancement was not significantly different between contrast ages because TPE reflects flow per unit of blood volume.25 The wash-in rate of PFB was significantly faster than that of SHM, and the signal intensity of PFB increased faster during the same TPE.
Certain artifacts exclusively related to contrast agent usage can affect CEUS image quality and interpretation. Pseudoenhancement caused by nonlinear propagation artifact can be visualized in scan areas with no true enhancement because of nonlinear propagation of ultrasound waves.30 This pseudoenhancement is generally caused by a high concentration of microbubbles particularly situated within the vascular lumen that can generate false enhancement in tissues.30 In the present study, this artifact was not observed on CEUS with either contrast agent because only recommended doses of the agents were used and there was no vessel large enough to generate the artifact in the scan area.
Quantitative parameters of CEUS can represent blood volume and blood flow velocity of the organ without the need of radiation exposure, unlike those of contrast-enhanced CT. A previous study19 investigated the effect of a single bolus injection versus continuous infusion of PFB for CEUS of the pancreas in dogs. In that study, the MI was set at 0.21, similar to the MI used for PFB in the present study (0.22). The median PI of the pancreas was 100.9 and 77.6 dB after bolus injection and continuous infusion, respectively.19 Those median PI values are lower than the values obtained with PFB in the present study, even though the same doses (0.015 mL/kg) and similar MI (0.21) of PFB were used. However, dogs in the previous study20 (11 to 18 kg) were larger than the dogs of our study (6.8 to 10.2 kg). In addition, the difference in CEUS quantitative parameters between studies can be attributed to the effect of various factors, including ultrasound machine, bolus injection rate, blood pressure, and cardiac output. According to the manufacturers' instructions for ultrasound contrast agents, the appropriate settings for frame rate, transmitted frequency, and location of focus are different.4
The present study had some limitations. First, only a small number of dogs of a single breed were used. Second, no histologic examinations were performed to confirm that the pancreas was histologically normal. Although the dogs were deemed healthy on the basis of medical history and various laboratory tests, the possibility of minor lesions could not be completely ruled out. Third, CEUS was performed on the pancreatic body but not on the left and right lobes. Because our study aimed to compare the CEUS features of SHM and PFB, CEUS was performed only on the pancreatic body to evaluate the CEUS images of the region from wash-in to washout of contrast medium. The pancreatic body was selected for CEUS because this region is always visualized clearly in healthy dogs and almost the same region can be scanned consistently on the basis of the landmark regardless of the dogs or contrast agents. In addition, the effect of the artifact generated from the gastrointestinal gas on CEUS analysis could be minimized in the pancreatic body. Finally, CEUS was not performed on dogs with pancreatic diseases. In dogs with pancreatic diseases, CEUS might be useful for further evaluating pancreatic lesions identified on conventional ultrasonography, and real-time CEUS of pancreatic lesions can be performed with a first injection of contrast agent, followed by qualitative evaluation following a second injection.20,28
Overall, the present study of pancreatic CEUS images enhanced with SHM and PFB in healthy dogs showed that both contrast agents had a similar TPE; however, PFB provided higher values of PI, wash-in rate, and AUC. In a future study, the clinical usefulness of PFB and SHM, including detectability of and sensitivity to early ischemic lesions, should be assessed with both agents in dogs with pancreatic diseases.
Acknowledgments
Funded by the Animal Medical Institute of Chonnam National University and the Basic Science Research Program through the National Research Foundation of Korea. Also funded by the Ministry of Science, ICT, and Future Planning (grant No. NRF-2018R1A2B6006775).
The authors declare that there were no conflicts of interest. The authors thank Jinkyung Park for statistical analysis.
Abbreviations
| AUC | Area under the curve |
| CEUS | Contrast-enhanced ultrasonography |
| MI | Mechanical index |
| PFB | Perfluorobutane |
| PI | Peak intensity |
| ROI | Region of interest |
| SHM | Sulfur hexafluoride microbubbles |
| TIC | Time-intensity curve |
| TPE | Time to peak enhancement |
Footnotes
Jurox, Rutherford, NSW, Australia.
Terrell, Piramal Critical Care, Bethlehem, Pa.
Prosound Alpha 7, Hitachi-Aloka, Tokyo, Japan.
SonoVue, Bracco Imaging, Milan, Italy.
Sonazoid, GE Healthcare, Oslo, Norway.
Sodium chloride injection, Daihan, Seoul, South Korea.
SOP-ALPHA7-14, Hitachi-Aloka, Tokyo, Japan.
SPSS Statistics, version 25, IBM Corp, Armonk, NY.
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Appendix
Qualitative scoring system used to evaluate CEUS features of the pancreas in healthy dogs.
| Feature | Score |
|---|---|
| Homogeneity of pancreatic parenchyma | |
| Entirely homogeneous enhancement | 3 |
| Hypoenhanced area making up < 25% of the parenchyma | 2 |
| Hypoenhanced area making up ≥ 25% of the parenchyma | 1 |
| Conspicuity of pancreatic signal relative to background | |
| Clearly distinguishable because of sufficient signal brightness of the parenchyma | 3 |
| Poorly distinguishable because of insufficient signal brightness of the parenchyma | 2 |
| Indistinguishable because of insufficient enhancement of the parenchyma | 1 |
