Traditional contrast-enhanced ultrasonography is based on the principle of second harmonic imaging. Although helpful, second harmonic imaging provides limited improvement in sensitivity for the detection of contrast agents. Such technology also is also unable to separate the acoustic signals returning from tissue from those returning from the contrast agent; therefore, the acoustic signals from tissue and contrast agents are combined, limiting the specificity or visible uniqueness of a contrast agent.
Recent advances in contrast-enhanced ultrasonography have led to the development of cadence CPS technology.a Contrast pulse sequencing simultaneously processes received signals from multiple transmitted pulses of varying amplitude modulation and phase. Control of pulse amplitude and phase allows the detection of the nonlinear fundamental and higher-order harmonic signals that are generated by the contrast agent exclusively. This technology enables imaging at higher frequencies than traditional methods, providing improved spatial and contrast resolution. It also provides the capability to specifically separate or link the signals received from the contrast agent and tissues, allowing clinicians to selectively view low MI tissue, contrast, or combined modes without imaging in a high MI mode.1
Fundamental B-mode ultrasonography historically has been the primary imaging modality used for assessment of pancreatic disease in animals. Acute pancreatitis is particularly common in dogs and can lead to vascular compromise, pancreatic edema, and hemor-rhage.2 Pancreatic changes can manifest sonographi-cally in various appearances depending on the severity and chronicity of the disease.3 The sonographic finding of a visibly normal pancreas in a patient with clinical criteria suggestive of pancreatitis does not preclude a diagnosis. Pancreatitis can have an unpredictable course, and prognosis is difficult to ascertain.4 Pancreatic neoplasia can also have a similar appearance, making it challenging to differentiate from mass-forming pancreatitis, pancreatic abscessation, or pseudocyst formation.3,4 Fundamental B-mode ultrasonography is also a routine part of the assessment of pathological conditions involving the gastrointestinal tract. Although ultrasonography is sensitive for the detection of intussusceptions and masses, the most common sonographic finding, wall thickening, is a nonspecific finding and can be seen with inflammatory, infectious, and neoplastic causes.5
Researchers in human medicine are investigating the use of contrast-enhanced ultrasonography for the detection and differentiation of diseases of the pancreas and gastrointestinal tract.6–21 In veterinary medicine, use of this imaging technology has mainly been limited to the evaluation of the liver and spleen. Published reports describe the use of contrast-enhanced ultrasonography to quantify healthy vascular perfusion in the liver,22 kidney,23 spleen,24 and prostate25,26; to characterize perfusion patterns of lesions within the liver,27,28 spleen,28,29 and kidney30; for the diagnosis of portosystemic shunts31; and to characterize vascular patterns within lymphomatous lymph nodes.32 To our knowledge, there have been no reports in the veterinary literature on the use of contrast-enhanced ultrasonography for the assessment of the pancreas or gastrointestinal tract in dogs. The purpose of the study reported here was to investigate contrast-enhanced ultrasonography as a minimally invasive method for evaluating perfusion patterns in the pancreas and duodenum, with comparison to adjacent liver tissue in healthy dogs.
Materials and Methods
Dogs—Eight clinically normal adult dogs (5 females and 3 males) weighing between 7 and 25 kg were enrolled in the study. Dogs were owned by the faculty and staff of the Kansas State University Veterinary Medical Teaching Hospital, who provided written consent for participation. Owners were asked to withhold food from their dogs for at least 12 hours prior to the study start. All dogs were judged to be free of clinical signs related to gastrointestinal and pancreatic disease. Results of a CBC and differential WBC count performed prior to ultrasonography were unremarkable, and serum lipase and amylase activities were within reference limits in all dogs. The study protocol was approved by and conformed to guidelines established by the Kansas State University Institutional Animal Care and Use Committee.
Imaging preparations—In each dog, an IV catheter was placed in a cephalic vein (n = 7 dogs) or saphenous vein (1). Seven dogs were sedated with a combination of acepromazine maleateb (0.01 mg/kg) and butorphanol tartratec (0.08 mg/kg), which was administered IV before ultrasonography. One dog did not require sedation and underwent ultrasonography with manual restraint.
Ultrasonography—Prior to contrast medium administration, complete sonographic evaluation of the pancreas, duodenum, and liver was performed by use of fundamental B-mode ultrasonography. No evidence of focal or diffuse abnormalities involving any of the 3 organs of interest was seen. Each dog was then positioned in left lateral recumbency, and the right pancreatic limb, proximal portion of the descending duodenum, and liver were identified by use of a right intercostal approach. Microbubble contrast mediumd was administered via injection into a direct access port connected to the IV catheter in 0.2-mL boluses. Each bolus was immediately followed by a flush consisting of 3 mL of saline (0.9% NaCl) solution. The dose of contrast medium was independent of the dog's body weight, and each dog received a minimum of 2 injections in separate boluses.
Immediately following each contrast medium injection, sonographic evaluation of the right pancreatic limb, proximal portion of the descending duodenum, and adjacent liver were performed by use of the right intercostal acoustic window. Following sonographic evaluation and prior to the administration of an additional bolus, the power output was adjusted to 100% and the organs of interest were scanned by use of fundamental B-mode ultrasonography to destroy residual contrast medium microbubbles. B-mode scanning was continued for approximately 2 minutes or until background echogenicity of each organ appeared similar to that prior to contrast medium injection. Imaging was performed in all dogs at 7 MHz with a broadband linear array transducer coupled with a commercially available ultrasonographic system with cadence CPS technology.a Contrast imaging software developed by the manufacturer consisted of multipulse technology that detects the strong nonlinear fundamental signals and higher-order harmonic signals emitted exclusively by the contrast medium microbubbles.1
Contrast images were optimized at an MI ranging from 0.31 to 0.51, depending on the depth of field, 2 focal zones, and optimized gain. Image quality was determined to be best with the 2 focal zones placed at or just below the organs of interest, providing images with good resolution and minimal near-field artifacts. Dynamic acquisition of images was obtained at a rate of 16 frames/s for 120 seconds following each injection.
Contrast images were analyzed at 10 frames/s by use of an online integrated software programe that used ROIs to generate quantitative time-intensity curves. Separate ROIs of the pancreatic parenchyma, duodenal wall, and liver parenchyma were manually drawn by the same person each time. Regions of interest were drawn as large as reasonably achievable, avoiding adjacent major vessels such as the CrPDA and CrPDV. When respiratory or subject motion shifted the placement of a portion of an ROI or a complete ROI outside the organ of interest, the ROI was manually moved to an equivalent location within the entirety of the organ. If the organ of interest shifted out-side of the imaging field of view, the data points collected during the period in which the organ was not in the image were excluded from analysis.
The contrast imaging software program was used to calculate mean acoustic signal intensity for each ROI, frame, and organ. The mean acoustic signal intensities of the boluses (2 to 3 injections) for each organ were calculated and plotted against time. Five time-intensity curve parameters were obtained and used for statistical analysis: interval to contrast medium arrival, inflow rate, PI, TPI, and outflow rate. Interval to contrast medium arrival was defined as the time when the acoustic signal intensity reached 10% higher than baseline (precontrast). Inflow rate was calculated by performing linear regression on time points at which the mean acoustic signal enhancement was between 10% of baseline and 90% of PI. The mean PI for the duodenum, pancreas, and liver was the largest value recorded for each ROI in each dog. Interval to PI was calculated as interval from bolus injection to PI. Outflow rate was calculated by performing linear regression on time points at which the mean acoustic signal enhancement was between 90% of PI and 10% of baseline (pancreas and duodenum) or end of the data collection period (liver). Time-intensity curve analysis was performed by use of a commercially available spreadsheet program.f
Statistical analysis—Statistical analysis was performed by use of 1-way ANOVA with the Bonferroni multiple comparison testg to evaluate the means of the duodenum and pancreas relative to that of the liver for each of the 5 time-intensity curve parameters. Linear regression analysis was used to test for significant associations between pancreatic and duodenal data. For all analyses, values of P ≤ 0.05 were considered significant. Associations were deemed clinically relevant when linear regression yielded a high coefficient of determination (R2 > 0.70). Data are reported as mean ± SD.
Results
Dogs—No adverse effects were noticed in any dog during or immediately following ultrasonography. All 8 dogs were clinically normal 10 months after the study concluded.
Ultrasonography—The right intercostal approach to ultrasound probe placement provided an acoustic window for transverse plane imaging of the proximal portion of the descending duodenum just caudal to its cranial flexure, the right pancreatic limb, and the liver. In this acoustic window, the liver was the most dorsally located organ. The triangularly shaped right pancreatic limb was situated between the liver dorsally and the duodenum ventrally (Figure 1). In 3 dogs, a portion of the ascending colon was also seen in the same image. The colon was typically seen to the left (medial or deep) of the pancreas and duodenum.
Transverse fundamental B-mode ultrasonographic image of a healthy 7-year-old Border Collie. Images were obtained by use of a right intercostal acoustic window (dorsal is to the left, ventral is to the right, medial is toward the bottom of the image). The triangularly shaped right pancreatic limb (p) is situated between the mesenteric border of the descending duodenum ventrally (d), the liver dorsally (l), and a portion of the ascending colon medial to the pancreas (c). The anechoic pancreaticoduo-denal vein (asterisk) is also seen centrally within the pancreas.
Citation: American Journal of Veterinary Research 73, 3; 10.2460/ajvr.73.3.385
Following contrast medium administration, microbubbles were first seen arriving within the CrPDA of the pancreas. The CrPDA was located immediately adjacent to the pancreatic-duodenal interface. Contrast medium inflow and concentration within the capillary beds of the pancreatic parenchyma from the CrPDA ultimately yielded a sharply marginated and uniformly contrast-enhanced pancreas at PI (Figure 2). At PI, the CrPDA was well demarcated and hyper-echoic to the surrounding pancreatic parenchyma because of the continuing inflow and high concentration of new microbubbles. The anechoic non-contrast-enhanced CrPDV was immediately adjacent but typically dorsal to the CrPDA. The CrPDV was subjectively larger than the CrPDA. During pancreatic outflow, a continual decrease in parenchymal intensity occurred via contrast medium drainage into the CrPDV by way of the contrast medium-laden venous tributaries. During this time, the CrPDA was still visible, although less intense because of a decrease in microbubble replenishment.
Representative transverse contrast-enhanced ultrasonographic images of the pancreas in a 7-year-old Border Collie. Images were obtained by use of the same right intercostal acoustic window as in Figure 1. A—Image acquired during the wash-in phase 19 seconds after contrast medium injection. The contrast-enhanced CrPDA is indicated (arrow). B—At peak enhancement of the pancreas, obtained 26 seconds after contrast medium injection, there is concentration within the capillary beds of the pancreatic parenchyma yielding a sharply marginated and uniformly contrast-enhanced pancreas. The non-contrast-enhanced and anechoic CrPDV is visible superficial to but immediately adjacent to its arterial counterpart (arrow). Concurrent enhancement of the colon (medial to the pancreas) and duodenum (ventral to the pancreas) is also seen. C—At 27 seconds after contrast medium injection, pancreatic washout has already begun, with contrast medium drainage into the pancreaticoduodenal vein (arrow) by means of the contrast medium-laden venous tributaries. D—At 50 seconds, the decrease in pancreatic parenchymal intensity continues. At this phase, intense enhancement of the liver is seen because of its portal blood supply. See Figure 1 for key.
Citation: American Journal of Veterinary Research 73, 3; 10.2460/ajvr.73.3.385
Contrast agent enhancement of the serosal and mucosal layers of the duodenum was seen concurrently with the parenchymal phase of the pancreas. This enhancement was then followed by homogeneous enhancement of all duodenal wall layers at PI (Figure 3). Peak intensity and washout of contrast medium at the duodenal wall and pancreas subjectively occurred at the same time.
Representative transverse contrast-enhanced ultrasonographic images of the duodenum in a healthy 3-year-old French Bulldog. Images were obtained by use of the same right intercostal acoustic window as in Figures 1 and 2. Compared with the Border Collie, this dog had faster wash-in and washout times. Perfusion characteristics for the duodenum were similar to those for the pancreas because of the intimately coupled vascular supply. A—Wash-in phase image obtained 9 seconds after contrast medium injection. B—At the PI of contrast medium in the duodenum, obtained 17 seconds after medium administration, there is homogenous contrast enhancement of all duodenal wall layers. The non-contrast-enhancing anechoic duodenal lumen is evident (arrow). C—Washout phase image obtained 22 seconds after medium injection. D—Duodenal washout and liver enhancement continues 28 seconds after medium injection. See Figure 1 for key.
Citation: American Journal of Veterinary Research 73, 3; 10.2460/ajvr.73.3.385
The interval from contrast medium injection to first appearance within the liver was similar to the pancreas and duodenum because of the supply from the hepatic artery, which is a branch of the celiac artery. The PI in the liver subjectively appeared to occur much later than in the duodenum and pancreas. Inflow rate, TPI, and outflow rate of contrast medium were slower because of the portal blood supply.
Perfusion parameters—Calculated data were summarized (Table 1). Contrast medium arrived in the pancreas (mean ± SD interval, 7.00 ± 3.10 seconds) and duodenum (6.95 ± 2.91 seconds) faster than in the liver (11.78 ± 4.79 seconds), although the difference was not significant. Mean inflow and outflow rates were significantly (P ≤ 0.05) greater in the pancreas and duodenum than in the liver. Mean PI was similar among all 3 organs. Mean TPI was significantly (P ≤ 0.01) shorter for the pancreas and duodenum than for the liver.
Mean ± SD values of quantitative perfusion analysis parameters for the pancreas, duodenum, and liver in 8 clinically normal adult dogs.
| Parameter | Pancreas | R2 | Duodenum | Liver |
|---|---|---|---|---|
| Interval to contrast medium arrival (s) | 7.00 ± 3.10 | 0.95* | 6.95 ± 2.91 | 11.78 ± 4.79 |
| Inflow rate (dB/s) | 4.83 ± 1.57† | NS | 5.53 ± 3.74‡ | 1.57 ± 0.66 |
| PI (dB) | 21.27 ± 7.16 | 0.74* | 20.13 ± 6.75 | 19.67 ± 6.46 |
| TPI (s) | 13.16 ± 6.27‡ | 0.96* | 13.08 ± 6.16‡ | 26.63 ± 9.23 |
| Outflow rate (dB/s) | −1.83 ± 1.16† | 0.91* | −1.81 ± 1.62‡ | −0.12 ± 0.08 |
The R2 value pertains to the association between values for the duodenum and pancreas, as determined by means of linear regression.
Significant (P ≤ 0.05) association between values for the duodenum and pancreas.
Significant (P ≤ 0.05) difference between indicated value and the corresponding liver value.
Significant (P ≤ 0.01) difference between indicated value and the corresponding liver value.
NS = No significant correlation.
The pancreas and duodenum had similar perfusion values. Significant (P ≤ 0.05) associations were identified for interval to arrival, PI, TPI, and outflow rate of contrast medium. There was no significant association for inflow rate.
Discussion
The pancreas is uniquely comprised of both exocrine and endocrine tissue. The exocrine portion of the pancreas comprises the bulk of the gland, consisting of secretory acini that secrete digestive juices into the duodenum via a complex ductal system.33 The highly vascularized endocrine portion, the islets of Langerhans, are scattered throughout the gland, constituting only 1.8% of the total pancreatic volume in dogs but receiving 10% of the organ's total blood volume.34–36 The islets of Langerhans are responsible for the secretion of the hormones insulin, glucagon, and somatostatin.34
The blood supply to the pancreas arises from branches of the celiac and cranial mesenteric arteries. The cranial portion of the right lobe of the pancreas is supplied by the CrPDA, which is a terminal branch of the hepatic artery. The CrPDA joins with the caudal pancreaticoduodenal artery within the pancreas. The caudal pancreaticoduodenal artery supplies the caudal portion of the right lobe of the pancreas and is a branch of the cranial mesenteric artery. The left lobe of the pancreas is supplied primarily by the pancreatic branch of the splenic artery but also receives small branches from the hepatic artery and gastroduodenal artery, which is a distal branch of the hepatic artery. Small pancreatic branches directly from the celiac artery may supply a small portion of the left limb of the pancreas near its distal extremity.37 Tributaries of the major arteries of the pancreas penetrate the gland and arborize into 1 of 3 types of terminal afferent arterioles: capillary arterioles surrounding and supplying the exocrine acini (acinar arterioles), acapillary arterioles that supply the ductal system, and afferent arterioles supplying the capillary glomerulus of the islets of Langerhans (insular arterioles).
Efferent capillary venules from the exocrine acini and ductal system drain directly into the systemic circulation via interlobular veins. Efferent capillary venules radiating from the islets join the capillary network of the exocrine pancreas and then empty into the systemic circulation. This is called the insuloacinar portal system. There are virtually no efferent capillary venules from the islets that empty into the systemic circulation directly.38 Essentially, the microcirculatory tree of the pancreas in dogs can be classified into 2 parts: the portion supplying the parenchymal tissue and the portion supplying blood to the islets of Langerhans before drainage into the portal system.39
The descending duodenum is also supplied by the CrPDA and caudal pancreaticoduodenal artery.37 These arteries supply the wall of the duodenum by way of an arching arterial system. Upon entering the wall, smaller arterial branches encircle the gut in opposing directions, with the tips of these arteries meeting on the antimesenteric border of the gut. From the encircling arteries, smaller arteries perforate the intestinal wall and spread along the muscle bundles to supply the intestinal submucosa and mucosa.40 The submucosa contains blood vessels that course around the circumference of the lumen, supplying smaller tributaries to the mucosal intestinal villi.40,41 The intestinal villi have small arterioles and venules that interconnect with a system of multiple looping capillaries. Arterial blood flow into the villus and venous flow out of the villus are in directions opposite each other (countercurrent blood flow). Because of this arrangement, as much as 80% of the blood oxygen diffuses out of the arterioles directly into the adjacent venules without ever being carried in the blood to the tips of the villi. The walls of the arterioles are also highly muscular and therefore highly active in controlling villus blood flow.40 It is the mucosa with its extensive subepithelial capillary network that provides the major blood flow to the intestines, serving the secretory and absorptive functions of the gut.40,42
In the present study, the right intercostal approach to ultrasound probe placement was used successfully to evaluate the right pancreatic limb, proximal portion of the descending duodenum, and adjacent liver in the same image. The similar perfusion characteristics of the duodenum and pancreas seen can be explained by the organs' intimately coupled vascular supply. The interval to contrast medium arrival was similar for these 2 organs as well as for the liver. This similarity was expected because the hepatic artery, which is a branch of the celiac artery, supplies all 3 organs. Perfusion in the pancreas and duodenum was subjectively more closely comparable within each dog than between dogs, possibly owing to differences in dog size, age, basal metabolic rates, or subclinical pancreatic or duodenal disease. Because quantitative perfusion analyses of the remaining portions of the pancreas and duodenum were not performed, evaluation of the body and left limb of the pancreas and distal portion of the descending duodenum would be needed to further characterize global perfusion of these organs.
The significantly faster inflow rates, TPI, and outflow rates of contrast medium for the pancreas and duodenum, compared with those in the liver, were expected and may be explained by the liver's dual blood supply of the hepatic artery and portal vein. The PI of the liver is reportedly associated with the peak portal phase.22 The hepatic arterial phase peak is obscured by the overlapping initiation of the portal phase. Consequently, it is not surprising that organs fed exclusively by systemic arteries would have faster perfusion than the liver, which has a predominantly portal venous blood supply. The PI for the liver was similar to the pancreas and duodenum in the present study, indicating similar blood flow among these 3 organs. However, during early liver inflow of contrast medium and pancreatic and duodenal outflow, the 3 organs were only briefly isointense.
The sample used in the present study comprised small- to medium-sized dogs only, and this represents a limitation. The smaller-sized dogs typically had shorter intervals to contrast medium arrival and TPIs than the medium-sized dogs, which could have been caused by differences in blood volume, minute volume, blood pressure, heart rate, or length of microbubble travel from the site of injection to the area of imaging. Little information is available on the influence of interindividual variation on physiologic variables or even on perfusion or blood flow.43–46 The variability in perfusion data for the clinically normal dogs in the present study would likely be exceeded in a clinical setting, in which dogs would likely vary much more in cardiovascular characteristics such as cardiac output, vascular tone, hydration, and other factors affecting end-organ perfusion data.
Only 1 study dog had the IV catheter placed in a lateral saphenous vein instead of a cephalic vein. Compared with the other dogs, this dog likely had a longer interval to contrast medium arrival and slower inflow rate (because of microbubble dispersion), TPI, and outflow rate. Compared with other dogs of similar size that underwent the same sedation protocol, the dog with the lateral saphenous vein catheter had a slightly shorter interval to contrast medium arrival and faster inflow rate, TPI, and outflow rate. This again substantiates the interindividual differences in perfusion data between dogs, even after the effect of size is accounted for.
Doppler waveform analysis of the celiac and cranial mesenteric arteries in dogs has shown that during digestion, there is an increase in diastolic blood flow, mean velocity, and flow volume caused by postprandial vasodilation.45,46 Although it was requested that food be withheld from all dogs prior to the present study, the possibility that at least 1 dog had been fed without our knowledge cannot be eliminated. Feeding prior to the procedures performed could potentially lead to an artifactual reduction in the interval to arrival and TPI of contrast medium, with faster inflow and outflow rates.
The use of sedation could also explain variability in time-intensity curve data among dogs. Sedation was primarily used to facilitate dog compliance and to minimize respiratory motion for the required 2-minute data-acquisition period. Respiratory or subject motion can move the target organs outside the field of view or allow them to fluctuate outside and back into the field. This movement allows regions with fresh contrast medium microbubbles that were not previously insonified into the scanned image, resulting in an overall increase in acoustic signal intensity due to decreased contrast medium microbubble destruction.22 Ultimately, such motion could alter PIs but should not significantly affect the interval to contrast medium arrival, TPI, and inflow or outflow rates. Because sedation was used in our study, respiratory and subject motion was minimal and did not adversely affect image quality or data acquisition. In the clinical setting, contrast-enhanced ultrasonography has been used to subjectively evaluate vascular patterns and perfusion deficits (nonen-hanced regions) in debilitated dogs with conditions such as pancreatitis without the use of sedation. This is one of the great advantages of contrast-enhanced ultrasonography over CT.
Other factors affecting timing and intensity data were contrast medium dose, ultrasonographic settings, and administration technique. Standardized dosing options for ultrasonographic contrast media have not been established for veterinary patients. Bolus doses of the contrast medium used in the present study are usually determined empirically and applied to dogs within a body weight range rather than applied on a microliter-per-kilogram or milliliter-per-kilogram basis.
In the present study, 0.2-mL bolus doses of micro-bubble contrast medium were used for each dog regardless of body weight. This dose was chosen on the basis of a review of the veterinary literature and 1 coinvestigator's experience. The dogs used in our study were also considered to be within a narrow body weight range (small and medium breeds). In addition, during the image optimization process prior to the conduction of the study, the dose used was determined to provide good-quality contrast-enhanced ultrasonograms regardless of the size of the dog. With the use of only 1 dose, one might speculate that PI should be higher and flow rates faster in smaller dogs because of the larger number of microbubbles available to be insonified per total blood volume, but this would not be expected to affect the interval to contrast medium arrival or the TPI in these dogs. Smaller dogs in the present study had faster intervals to contrast medium arrival and faster TPIs than did larger dogs. It is not possible to determine whether contrast medium dose influenced these 2 parameters. Additional research needs to be conducted with a larger number of dogs of various body weights to evaluate the role use of a single set microbubble contrast medium bolus dosing regimen versus a microliter-per-kilogram or milliliter-per-kilogram dose has on time-intensity curve characteristics when a fixed ultrasound machine and contrast software with standardized settings are used.
Slight differences in focal zone locations, gain settings, and MIs used between dogs to obtain the best possible images could have caused differing effects on the contrast medium microbubbles in the study reported here. In our experience, body size also affects the depth of imaged organs and therefore the effective MI and contrast agent signal strength. The micro-bubble contrast medium used purportedly has rigid microspheres, and our imaging was performed with MIs well within the recommended range (MI, < 0.7). The interindividual setting differences likely had no important effect on study results. For this reason, contrast medium arrival intervals and TPIs should be consistent within each dog. External factors that could have affected slope or TPI include contrast medium injection pressure and timing of saline solution flush administration because hand injection was used and > 1 examiner was involved in contrast medium administration.
In human medicine, research is ongoing into the usefulness of contrast-enhanced ultrasonography to characterize pancreatitis and pancreatic neoplasms on the basis of perfusion patterns. As in dogs, inflammatory and neoplastic masses in humans can have a similar appearance when imaging techniques are used, making early detection and differentiation of these 2 categories of pancreatic disease important. The survival rate for individuals with certain pancreatic neoplasms, particularly carcinoma, is poor. Recently, investigators who used contrast ultrasonographic technology similar to ours evaluated quantitative perfusion analysis as a means to differentiate individuals with inflammatory masses associated with chronic pancreatitis from those with carcinomas.15 They found contrast medium arrival times to be significantly longer in patients with carcinomas than in those with inflammatory masses or healthy pancreata. The TPIs were slower and PIs lower in inflammatory and carcinomatous masses than in healthy pancreata, although there was no significant difference in PIs between the 2 diseases.
Another study16 involved comparison of CT, which is the gold standard in pancreatic imaging, with contrast-enhanced ultrasonography for the assessment of severity of acute pancreatitis in humans and for identification of pancreatic necrosis, which is associated with high morbidity and mortality rates in humans. In that study, necrosis was identified via CT in 8 patients, and contrast-enhanced ultrasonography revealed necrosis in all. Conventional fundamental B-mode ultrasonography was only able to detect necrosis in 2 of the 8 patients. However, contrast-enhanced ultrasonography had 2 false-positive results, which corresponded to fibrosis and small pseudocysts, suggesting that differentiation of these disease processes from necrosis could be difficult and that further investigation should be pursued.16
Pancreatic adenocarcinoma is the most common neoplastic condition of the exocrine pancreas in dogs and is the fifth most common malignancy in humans.4 Although insulinoma is an uncommon neuroendocrine tumor, it is the most common islet cell neoplasm in dogs.47 It is also one of the most commonly detected pancreatic endocrine tumors in humans.48 Pancreatic adenocarcinomas are generally considered to be hypovascular, and tumors of neuroendocrine origin, such as insulinoma, are typically hypervascular.9 The anatomic structure of the pancreas and small size of neuroendocrine tumors also make detection of these tumors with fundamental B-mode ultrasonography or CT difficult.8 Several studies10,11,14 have been conducted to examine contrast-enhanced ultrasonography for the purposes of discriminating pancreatic tumors. Overall, most carcinomas were observed to have absent to low contrast enhancement and vasculature, whereas neuroendocrine tumors had strong early contrast-enhancing effects with abundant vessels.10,11,14 In comparison with CT, contrast-enhanced ultrasonography is less invasive, is lower in cost, does not require ionizing radiation or anesthesia, can be easily repeated, and eliminates the need for injection of iodinated contrast media, which can be contraindicated in critically ill patients.
Contrast-enhanced ultrasonography may also have future clinical applications in the diagnosis or monitoring of therapeutic responses for dogs with vasculitides and other diseases of the gastrointestinal tract. Intestinal ischemia secondary to vascular insufficiency, thromboses, inflammatory conditions, or neoplastic infiltrations are just some of the conditions in which contrast-enhanced ultrasonography could be applicable. Dogs with chronic enteropathies reportedly have altered hemodynamics of the major arteries supplying the bowel, suggesting that contrast-enhanced ultrasonography could provide additional information useful for the diagnosis of canine inflammatory bowel disease, although additional research is needed to confirm this supposition.45,49
ABBREVIATIONS
| CPS | Contrast pulse sequencing |
| CrPDA | Cranial pancreaticoduodenal artery |
| CrPDV | Cranial pancreaticoduodenal vein |
| CT | Computed tomography |
| MI | Mechanical index |
| PI | Peak intensity |
| ROI | Region of interest |
| TPI | Time of peak intensity |
Acuson Sequoia C512 with 15L8w transducer, Siemens, Mountain View, Calif.
Acepromazine maleate, Boehringer Ingelheim, St Joseph, Mo.
Torbugesic, Fort Dodge Animal Health, Fort Dodge, Iowa.
Definity, Bristol-Myers Squibb Medical Imaging, North Billerica, Mass.
Axius ACQ autotracking contrast quantification, Siemens, Mountain View, Calif.
Microsoft Excel, Microsoft Corp, Redmond, Wash.
Prism, version 4 for Macintosh, GraphPad Software Inc, San Diego, Calif.
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